{"id":71222,"date":"2023-04-27T15:06:51","date_gmt":"2023-04-27T14:06:51","guid":{"rendered":"https:\/\/touchoncology.com\/?p=71222"},"modified":"2023-07-24T15:40:17","modified_gmt":"2023-07-24T14:40:17","slug":"teclistamab-monotherapy-for-the-treatment-of-adult-patients-with-relapsed-and-refractory-multiple-myeloma","status":"publish","type":"post","link":"https:\/\/touchoncology.com\/haematological-malignancies\/journal-articles\/teclistamab-monotherapy-for-the-treatment-of-adult-patients-with-relapsed-and-refractory-multiple-myeloma\/","title":{"rendered":"Teclistamab Monotherapy for the Treatment of Adult Patients with Relapsed and Refractory Multiple Myeloma"},"content":{"rendered":"

Multiple myeloma<\/span>\u00a0(MM<\/span>) is the\u00a0<\/span>second most common<\/span>\u00a0ha<\/span>ematological malignancy,<\/span>\u00a0with upwards of\u00a035,000<\/span>\u00a0diagnoses in the USA<\/span>\u00a0each year.1,2<\/sup><\/span>\u00a0<\/span>It remains a leading cause of blood cancer–<\/span>related mortality\u00a0worldwide<\/span>,<\/span>\u00a0and although therapeutic advances have allowed for significant improvements in the median overall survival,3,4<\/sup><\/span>\u00a0<\/span>the majority of patients still experience cycles of relapse that are eventually fatal<\/span>.5<\/sup><\/span>\u00a0While\u00a0<\/span>patients\u00a0with MM<\/span>\u00a0<\/span>are living longer,<\/span>\u00a0a subgroup with\u00a0<\/span>high-risk disease\u00a0at diagnosis<\/span><\/span>\u00a0still does<\/span>\u00a0poorly, with\u00a0a\u00a0<\/span>median overall survival<\/span>\u00a0of\u00a0<\/span>nearly<\/span>\u00a03<\/span>\u00a0years.<\/span><\/span><\/span>6<\/sup><\/span>\u00a0<\/span>Outcomes are also dismal in\u00a0<\/span>patients with\u00a0<\/span>disease that is refractory\u00a0<\/span>to the major modern therapies\u00a0including thalidomide analogue<\/span>s, proteosome inhibitors and anti-CD38 monoclonal antibodies<\/span><\/span><\/span>.7<\/sup><\/span>\u00a0Together, these unmet needs have driven the development of immunotherapy for\u00a0<\/span>relapsed\u00a0and\u00a0<\/span>refractory multiple myeloma<\/span>\u00a0(RRMM<\/span>)<\/span>.<\/p>\n

Toward<\/span>\u00a0this end, immune cell redirecting therapies were developed following the discovery of suitable MM cell-surface markers and novel drug engineering technologies. Chimeric antigen receptor\u00a0(CAR)-<\/span>T\u00a0<\/span>cells\u00a0<\/span><\/span><\/span>showed robust responses in RRMM\u00a0compared with\u00a0B cell maturation antigen (BCMA<\/span>),<\/span>\u00a0<\/span><\/span>leading\u00a0<\/span>to the approval of cellular therapies for\u00a0<\/span>MM<\/span>\u00a0\u2013<\/span>\u00a0idecabtagene<\/span>\u00a0vicleucel in\u00a02021\u00a0<\/span><\/span>and\u00a0<\/span>ciltacabtagene autoleucel<\/span>\u00a0in\u00a02022<\/span>.8\u201311<\/sup><\/span>\u00a0<\/span>Available data on\u00a0idecabtagene<\/span>\u00a0vicleucel<\/span>\u00a0and\u00a0ciltacabtagene autoleucel<\/span>\u00a0in RRMM, however, suggest that most\u00a0<\/span>patients will\u00a0<\/span>experience disease progression<\/span>\u00a0after initial response.9,11<\/sup><\/span><\/span>\u00a0Moreover, the need for patient-specific manufacturing and access to specialized cellular therapy centre<\/span>s continue to limit\u00a0CAR T<\/span>\u00a0cell access for patients with rapid disease progression or in\u00a0under-served<\/span>\u00a0areas.<\/p>\n

Successful adaptive immune redirection has also been shown with bispecific antibodies (BsAbs<\/span>) against various established and emerging MM\u00a0<\/span>cell targets.\u00a0<\/span>This review follows the\u00a0US Food and Drug Administration<\/span>\u00a0(<\/span>FDA)<\/span>\u00a0approval of\u00a0teclistamab \u2013 the<\/span>\u00a0first-in-kind commercially available BsAb for RRMM.12<\/sup><\/span>\u00a0<\/span>Teclistamab is a T\u00a0<\/span>cell-redirecting antibody that targets CD3 on the surface of T cells and\u00a0BCMA<\/span>\u00a0expressed on the surface of myeloma cells\u00a0(BCMA\u00d7<\/span>CD3)<\/span>. It was approved for use as monotherapy\u00a0i<\/span>n\u00a0<\/span>2022<\/span>\u00a0based on<\/span>\u00a0data from the MajesTEC-1 trial published in June 2022.<\/span><\/span>13<\/sup><\/span>\u00a0Teclistama<\/span>b and similar agents in development enable T cell redirection with similar potency to\u00a0CAR T<\/span>\u00a0cells but without the delay required for patient-specific manufacturing.<\/p>\n

In this article<\/span>, we review the mechanism of action of this<\/span>\u00a0BCMA\u00d7<\/span>CD3 antibody, the clinical data supporting the approval of teclistamab and its impact on the treatment paradigms for RRMM.<\/p>\n

Mechanisms of\u00a0a<\/span>ction<\/h1>\n

Overview of\u00a0B cell maturation antigen\u00a0<\/span>as a target<\/h2>\n

BCMA, also known as TNFRSF-17 or CD269, is a small transmembrane protein member of\u00a0the\u00a0<\/span>tumou<\/span>r necrosis factor\u00a0(TNF)<\/span><\/span>\u00a0<\/span>receptor superfamily. It is selectively induced during\u00a0plasma cell<\/span>\u00a0(PC<\/span>) differentiation,14<\/sup><\/span>\u00a0with transcription and cell-surface expression concentrated in subsets of mature B\u00a0<\/span>cells,\u00a0PC<\/span>s and plasmacytoid dendritic cells.15,16<\/sup><\/span>\u00a0Select\u00a0<\/span>datasets<\/span>\u00a0<\/span>have also suggested low-level transcription on neurons and astrocytes,17<\/sup><\/span>\u00a0though other studies have not supported this association.18,19<\/sup><\/span><\/p>\n

BCMA has two ligands, BAFF\/BLys and APRIL, which are integral to maintaining\u00a0bone marrow\u00a0<\/span>PC<\/span>\u00a0survival and homeostasis\u00a0(as\u00a0<\/span>reviewed in\u00a0Eckhert et al. and Romano et al.)<\/span>.20,21<\/sup><\/span>\u00a0<\/span>Stimulation with APRIL or BAFF activates\u00a0the\u00a0<\/span>NF-\u03ba<\/span>B, AKT and\u00a0mitogen-activated protein kinase<\/span>\u00a0(<\/span>MAPK)<\/span>8\/c-Jun N-terminal kinase (<\/span>JNK)<\/span>\u00a0signall<\/span>ing cascades,<\/span>\u00a0resulting in the upregulation of anti-apoptotic proteins,22<\/sup><\/span>\u00a0adhesion molecules, cell-cycle regulators, angiogenesis factors, immunosuppressive molecules and inflammatory cytokines\u00a0<\/span>(Figure 1A<\/span><\/span><\/span>)<\/span>.23\u201326<\/sup><\/span>\u00a0Both ligands also bind to\u00a0transmembrane activator calcium modulator and cyclophilin ligand interactor<\/span>\u00a0(<\/span>TACI)<\/span>, a larger homologue<\/span>\u00a0receptor of the\u00a0<\/span>TNF\u00a0<\/span>receptor<\/span>\u00a0superfamily, and mediate PC differentiation and T cell-independent\u00a0immunoglobulin (Ig)<\/span>\u00a0<\/span>isotype switching.27<\/sup><\/span>\u00a0The role of BCMA activation, however, is restricted to\u00a0maintaining<\/span>\u00a0PCs and antigen presentation by B cells.26<\/sup><\/span>\u00a0BCMA has a soluble form derived from\u00a0the\u00a0<\/span>cleavage of the membrane BCMA mediated by \u03b3-secretase.28<\/sup><\/span>\u00a0This soluble form has shown to sequester BAFF and mediate immunosuppression by preventing normal B\u00a0<\/span>cell and\u00a0<\/span>PC\u00a0<\/span>development.29<\/sup><\/span><\/p>\n

\u00a0\"\"<\/p>\n

BCMA is overexpressed in\u00a0MM,<\/span><\/span>30<\/sup><\/span>\u00a0and NF-\u03ba<\/span>B overactivation\u00a0i<\/span>s a hallmark of MM tumou<\/span>rigenesis.31<\/sup><\/span>\u00a0<\/span>In patients with MM,\u00a0<\/span>s<\/span>oluble BCMA is also significantly elevated\u00a0<\/span>compared\u00a0with\u00a0<\/span>healthy individuals,<\/span>\u00a0and higher\u00a0<\/span>soluble BCM<\/span><\/span>A\u00a0(sBCMA)\u00a0<\/span><\/span>levels correlate with immune paresis, disease burden and adverse outcomes.28,32<\/sup><\/span>\u00a0Preclinical studies demonstrated that antibodies with ligand–<\/span>blocking activity could promote cytotoxicity\u00a0in\u00a0<\/span>MM cell lines as naked antibodies or as antibody\u2013<\/span>drug conjugates by inhibiting APRIL-dependent activation of NF-\u03ba<\/span>B in a dose-dependent manner\u00a0in vitro<\/em><\/span>.33<\/sup><\/span>\u00a0BCMA was later validated as a suitable\u00a0CAR T<\/span>\u00a0target.15<\/sup><\/span>\u00a0Altogether, these studies paved the way\u00a0<\/span>for<\/span>\u00a0the development and clinical investigation of anti-BCMA antibody\u2013<\/span>drug conjugates,\u00a0CAR T<\/span>\u00a0and now BsAb therapies against RRMM\u00a0<\/span>(<\/span>Figure 1B<\/span><\/span><\/span>).<\/span><\/p>\n

<\/span>Bispecific antibody therapy development for\u00a0relapsed\u00a0and\u00a0<\/span>refractory multiple myeloma<\/span><\/span><\/h2>\n

BsAbs are T\u00a0<\/span>cell–<\/span>engaging (TCE<\/span>) therapies designed to redirect T\u00a0<\/span>cell cytotoxicity towards cell-surface tumou<\/span>r antigens\u00a0(<\/span>Figure 1B<\/span><\/span><\/span>)<\/span>. TCE therapies have been developed in various formats, including bispecific\u00a0<\/span><\/span>Ig<\/span>G-like antibodies or shorter molecules comprising<\/span>\u00a0two linked antigen-binding domains configured as single-chain variable fragments,<\/span>\u00a0such as<\/span><\/span>\u00a0<\/span>bispecific T\u00a0<\/span>cell engagers<\/span>\u00a0(<\/span>BiTEs<\/span>).34<\/sup><\/span>\u00a0BsAbs were originally proposed in the early\u00a01960<\/span>s<\/span>\u00a0but only developed35<\/sup><\/span>\u00a0and studied clinically36<\/sup><\/span>\u00a0years later. The favou<\/span>rable clinical efficacy of the blinatumomab (<\/span>CD19<\/span><\/span>\u00d7<\/span>CD3<\/span>\u00a0BiTE in relapsed<\/span>\u00a0<\/span>B-cell acute lymphoblastic leukaemia<\/span><\/span>) published in\u00a02017<\/span>37<\/sup><\/span>\u00a0generated interest in BsAb development for other ha<\/span>ematologic malignancies.34<\/sup><\/span><\/p>\n

<\/span>An anti-BCMA BiTE construct, the<\/span>\u00a0BCMA\u00d7<\/span>CD3 AMG420,<\/span><\/span>\u00a0yielded encouraging preclinical38<\/sup><\/span>\u00a0and clinical activity against RRMM.39<\/sup><\/span>\u00a0The need for a\u00a04<\/span>–<\/span>week<\/span>\u00a0continuous infusion due to the short half-life of BiTEs shifted\u00a0the\u00a0<\/span>focus\u00a0on<\/span>to longer half-life, full-length IgG molecules.40<\/sup><\/span>\u00a0Several BCMA-targeting BsAbs have since been developed and tested in various clinical settings and combinations,<\/span>\u00a0and are reviewed by Moreau\u00a0and<\/span>\u00a0<\/span>Touzeau.41<\/sup><\/span>\u00a0Of these, teclistamab has been studied in the MajesTEC<\/span>\u00a0trial series and will be further described in the following\u00a0section<\/span>.<\/p>\n

BsAbs against other emerging targets in RRMM are also being investigated. Talquetamab, a\u00a0G protein-coupled receptor\u00a0class C, group 5, member D (GPR<\/span><\/span>C<\/span>5D)<\/span>\u00d7<\/span>CD3\u00a0BsAb<\/span>, showed promising tolerability and efficacy in a phase\u00a0<\/span>1<\/span><\/span><\/span><\/span>\u00a0trial (<\/span>MonumenTAL<\/span>-1)42,43<\/sup><\/span>\u00a0<\/span>and is also being studied in combination with daratumumab (<\/span>TRIMM-2,44<\/sup><\/span>\u00a0MonumenTAL-345<\/sup><\/span><\/span>) and several other agents (MonumenTAL-2).46<\/sup><\/span>\u00a0Cevostamab, an\u00a0Fc receptor-homologue 5\u00a0(FCHR5)<\/span><\/span><\/span>\u00d7<\/span>CD3\u00a0BsAb<\/span><\/span>, has also demonstrated safety and promising efficacy in an on–<\/span>going phase\u00a0<\/span><\/span><\/span><\/span>1<\/span>\u00a0study (ClinicalTrials.gov\u00a0<\/span>identifier: NCT<\/span>03275103).47<\/sup><\/span>\u00a0T<\/span>his<\/span>\u00a0emergence of non-BCMA TCE targets is likely to introduce additional options and complexity in the care of heavily refractory patients.<\/p>\n

Teclistamab in\u00a0relapsed\u00a0and<\/span>\u00a0refractory multiple myeloma<\/span><\/span><\/h1>\n

Clinical investigation<\/h2>\n

Teclistamab (also\u00a0known<\/span>\u00a0as\u00a0<\/span>JNJ-64007957, Ab-957 and JNJ-7957) is a humanized\u00a0Ig<\/span>G4-proline, alanine, alanine (IgG4-PAA) bispecific DuoBody\u00ae<\/sup><\/span><\/span>\u00a0antibody\u00a0<\/span>(Genmab,\u00a0Copenhagen<\/span>, Denmark<\/span><\/span>),<\/span><\/span>\u00a0whose\u00a0<\/span><\/span>in vitro<\/em><\/span>\u00a0efficacy\u00a0was\u00a0<\/span>first shown in\u00a02016.<\/span><\/span>48,49<\/sup><\/span>\u00a0<\/span>The first in–<\/span>human trial with teclistamab, MajesTEC-1, was an open-label, single-arm phase\u00a01\/2<\/span>\u00a0(p<\/span>hase\u00a01<\/span>\u00a0ClinicalTrials.gov identifier: NCT03145181;\u00a0p<\/span>hase\u00a02\u00a0<\/span>ClinicalTrials.gov identifier: NCT03145181<\/span><\/span>)\u00a0<\/span><\/span>trial<\/span>\u00a0that evaluated intravenous\u00a0(phase\u00a01<\/span>)<\/span> and subcutaneous\u00a0(phase\u00a01<\/span>\u00a0and\u00a02<\/span>)<\/span>\u00a0administration.<\/span>1,13,50,51<\/sup><\/span><\/span><\/span><\/span>\u00a0<\/span><\/span><\/span><\/span><\/span><\/span><\/span>Participants were<\/span>\u00a0r<\/span>efractory to thalidomide analogue<\/span>s and proteosome inhibitors;<\/span>\u00a0most patients (93%) had also progressed on an anti-CD38 agent.51<\/sup><\/span><\/span>\u00a0<\/span>Doses ranging from\u00a0<\/span><\/span><\/span><\/span><\/span>0.3 \u00b5g\/kg to 3000 \u00b5g\/kg<\/span><\/span>\u00a0<\/span>were evaluated.51<\/sup><\/span>\u00a0<\/span>At most levels<\/span>, a step-up dosing approach\u00a0was used<\/span>,<\/span>\u00a0in which\u00a01\u2013<\/span><\/span><\/span>3<\/span>\u00a0smaller quantities were administered over several days prior to the first full dose<\/span><\/span>, with the intent of more gradually activating T cells and reducing the risk of severe\u00a0cytokine release syndrome\u00a0(CRS<\/span>)<\/span><\/span><\/span>. Clinical responses were observed beginning at\u00a038.4<\/span>\u00a0\u00b5g\/kg<\/span>. No maximum tolerated dose was identified, and a recommended phase\u00a0<\/span><\/span><\/span><\/span>2<\/span>\u00a0dose of\u00a01.5<\/span>\u00a0mg\/kg<\/span>\u00a0weekly, administered as a subcutaneous injection, was determined based on\u00a0the\u00a0<\/span>combined safety, efficacy, pharmacokinetic and pharmacodynamic profiles\u00a0of\u00a0teclistamab<\/span><\/span>. In total,\u00a0<\/span>165<\/span>\u00a0<\/span><\/span>patients\u00a0<\/span>enrolled in phase\u00a0<\/span><\/span><\/span><\/span>1<\/span>\u00a0and<\/span>\u00a0<\/span><\/span>2<\/span>\u00a0of the\u00a0<\/span>MajesTEC<\/span>-1\u00a0trial\u00a0<\/span>received teclistamab at the\u00a0recommended phase\u00a02<\/span>\u00a0dose<\/span>. Patients received two step-up doses of 0.06\u00a0mg\/kg\u00a0<\/span>and\u00a00.3<\/span>\u00a0mg\/kg<\/span>, which were separated by\u00a02<\/span><\/span>\u2013<\/span>4<\/span>\u00a0days<\/span>\u00a0and were completed\u00a02<\/span><\/span>\u2013<\/span>4<\/span>\u00a0days<\/span>\u00a0before the first full teclistamab dose\u00a0was administered<\/span>. Patients with confirmed partial response or better were permitted to switch to\u00a02-weekly<\/span>\u00a0<\/span>dosing<\/span>.13,52<\/sup><\/span><\/p>\n

With a median follow-up of\u00a014.1<\/span>\u00a0months<\/span>, the overall response rate was 63.0%, with\u00a065<\/span>\u00a0patients<\/span>\u00a0(39.4%) having a complete response or better. A total of\u00a044<\/span>\u00a0patients<\/span>\u00a0(26.7%)\u00a0had<\/span>\u00a0no\u00a0minimal residual disease<\/span><\/span>; the negativity rate\u00a0of\u00a0minimal residual disease\u00a0<\/span><\/span>among the patients with a complete response or better was\u00a046.0<\/span><\/span>%<\/span>. Responses occurred rapidly, with a median of\u00a01.2<\/span>\u00a0months<\/span>\u00a0until first response.<\/p>\n

The\u00a0Kaplan\u2013Meier<\/span>\u00a0estimate of maintenance of response for at least\u00a012<\/span>\u00a0months<\/span>\u00a0was\u00a068.5<\/span>%<\/span>\u00a0(95%<\/span>\u00a0<\/span>confidence interval [CI]\u00a0<\/span>57.7<\/span><\/span>\u2013<\/span>77.1)<\/span>. The median duration of response was\u00a018.4<\/span>\u00a0months<\/span>\u00a0(95<\/span>%\u00a0CI<\/span><\/span>\u00a014.9\u2013<\/span>not estimable). The median progression-free survival was\u00a011.3<\/span>\u00a0months<\/span>\u00a0(95%<\/span>\u00a0CI<\/span>\u00a08.8<\/span><\/span>\u2013<\/span>17.1)<\/span>.<\/p>\n

<\/span>Safety and infection risk13<\/sup><\/span><\/span><\/h2>\n

As with\u00a0CAR T<\/span>\u00a0cells,\u00a0<\/span><\/span>CRS<\/span>\u00a0and\u00a0immune effector cell-associated neurotoxicity syndrome<\/span>\u00a0(ICANS<\/span>) are important\u00a0adverse effects\u00a0<\/span>of teclistamab and occurr<\/span>ed in\u00a072.1<\/span>%<\/span><\/span><\/span>\u00a0and\u00a0<\/span>3.0<\/span>%<\/span>\u00a0of\u00a0<\/span>patients<\/span>, respectively<\/span>. These risks are confined to the initial doses and typically occur\u00a02\u00a0<\/span>or\u00a03\u00a0<\/span>days following the inciting dose. Inpatient monitoring at the time of the two step-up\u00a0dose\u00a0<\/span>and first full dose\u00a0of\u00a0teclistamab\u00a0<\/span><\/span>is recommended in the\u00a0<\/span>FDA prescribing information\u00a0<\/span>to enable\u00a0the<\/span>\u00a0prompt management of CRS.53<\/sup><\/span>\u00a0<\/span>Roughly half of\u00a0the<\/span>\u00a0patients who experienced CRS, or\u00a036<\/span>%<\/span>\u00a0of\u00a0<\/span>phase\u00a02<\/span>\u00a0participants<\/span>, received tocilizumab;<\/span>\u00a0<\/span>8.5<\/span>%<\/span>\u00a0of subjects received corticosteroids<\/span>\u00a0for CRS or ICANS<\/span>\u00a0management,\u00a0<\/span>thus warranting\u00a0<\/span>the\u00a0<\/span>availability\u00a0<\/span>of anti-interleukin<\/span><\/span>-6 agent upon therapy initiation<\/span>.\u00a0<\/span>Patients who respond to teclistamab are not at\u00a0an\u00a0<\/span>on–<\/span>going risk of CRS or ICANS with long-term dosing. If therapy is interrupted for longer than a month, however, repeat step–<\/span>up dosing is advised.54<\/sup><\/span><\/span><\/p>\n

Infections were major\u00a0adverse events<\/span>\u00a0in the\u00a0<\/span>MajesTEC-1\u00a0trial\u00a0<\/span>and occurred throughout\u00a0the\u00a0<\/span>therapy<\/span>.50<\/sup><\/span>\u00a0<\/span>A total of\u00a0<\/span>126<\/span>\u00a0patients<\/span>\u00a0(76.4%) reported at least one infectious event,<\/span>\u00a0with\u00a074<\/span>\u00a0<\/span>(44.8%) experiencing grade\u00a0<\/span>3<\/span>\u00a0or\u00a0<\/span>4<\/span>\u00a0infections<\/span>. Notably,\u00a0coronavirus disease 2019 (<\/span>COVID-19)<\/span>\u00a0was frequent and led to on-study mortality in 12 of the 165 participants, though many of the fatal cases occurred in the early phase of the pandemic. Other viral (cytomegalovirus<\/span><\/span><\/span>,\u00a0<\/span>JC virus<\/span>), bacterial and fungal events were also reported. Six (3.6%) patients developed\u00a0P<\/em><\/span>neumocystis jirovecii<\/em>\u00a0pneumonia. Among the 19 on-study deaths due to adverse events, 14 were attributed to infection (12 due to COVID-19,\u00a0one<\/span>\u00a0due to progressive multifocal leukoencephalopathy from JC\u00a0v<\/span>irus infection,<\/span>\u00a0and\u00a0one<\/span>\u00a0due to streptococcal pneumonia). Hypogammaglobulina<\/span>emia developed in\u00a074.5%\u00a0of<\/span><\/span>\u00a0patients<\/span>\u00a0(essentially all patients who responded to therapy and received long-term teclistamab), which likely contributed to\u00a0the\u00a0<\/span>risk of infection.\u00a0<\/span>The\u00a0<\/span>FDA prescribing information recommends\u00a0<\/span>varicella zoster virus\u00a0<\/span><\/span><\/span>prophylaxis.53<\/sup><\/span><\/span>\u00a0Additional prophylaxis against\u00a0P<\/em><\/span>neumocystis jirovecii<\/em>\u00a0pneumonia,<\/span>\u00a0<\/span>and\u00a0Ig\u00a0<\/span>replacement therapy t<\/span><\/span>o maintain IgG\u00a0levels\u00a0<\/span><\/span><\/span>><\/span>400<\/span>\u00a0mg\/dL,<\/span>\u00a0should be\u00a0<\/span>considered<\/span><\/span><\/span>.54<\/sup><\/span>\u00a0In our view, these measures are<\/span>\u00a0essential\u00a0considering the magnitude of infection risk<\/span>.\u00a0<\/span>Interventions to protect against COVID-19 are also prudent, including vaccination and proactive use of anti-virals when symptomatic infections develop. Though patients on teclistamab are not expected to mount antibody responses to vaccination, vaccine-induced T cell responses have been observed and may be clinically protective.55<\/sup><\/span><\/p>\n

<\/span>Ha<\/span>ematologic\u00a0<\/span>toxicity is commonly observed. Grade\u00a0<\/span>3<\/span>\u00a0or\u00a0<\/span>4<\/span>\u00a0neutrop<\/span>enia, ana<\/span>emia and thrombocytop<\/span>enia\u00a0were\u00a0<\/span>reported in 64.2%<\/span>,\u00a037.0%<\/span><\/span><\/span>\u00a0and\u00a0<\/span>21.2<\/span>%\u00a0of<\/span><\/span>\u00a0trial<\/span>\u00a0participants, respectively. Of the\u00a0117<\/span>\u00a0patients<\/span>\u00a0in whom neutrop<\/span>enia developed, 91 received granulocyte colony-stimulating factor\u00a0<\/span>therapy at the investigator\u2019s\u00a0<\/span>discretion<\/span>.13,50,51<\/sup><\/span>\u00a0In our experience, neutropenia with teclistamab is idiosyncratic, occurring intermittently throughout treatment, and can be successfully managed with occasional dose\u00a0<\/span>holding and\u00a0the\u00a0<\/span>administration of filgrastim.<\/p>\n

Efficacy correlations and drug\u2013<\/span>drug synergy<\/h2>\n

Various baseline immune, tumou<\/span>r and clinical factors are associated with the clinical efficacy of teclistamab.\u00a0<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span>52<\/sup><\/span>\u00a0In MajesTEC-1, response rates and progression-free survival correlated positively with recipient peripheral T cell counts and a naive CD8 T cell phenotype and inversely with burden of regulatory and exhausted (PD-1-, CD38-, and TIM-3-expressing) T cells.50<\/sup><\/span><\/span><\/span>\u00a0These findings are consistent with\u00a0preclinical<\/span>\u00a0predictions56<\/sup><\/span>\u00a0and with associations seen in other TCE\u00a0<\/span>therapies, including BCMA\u00a0CAR T<\/span>.<\/span>57\u201359<\/sup><\/span><\/span><\/span>\u00a0The depletion of na\u00efve and early–<\/span>memory T\u00a0<\/span>cells,<\/span>\u00a0along with the increasing frequency of an exhausted immune phenotype,<\/span>\u00a0are common features of advanced MM and of heavily pretreated patients. The intrinsic reliance on host immunity raises the question of whether TCE\u00a0<\/span>therapies should be used in early lines of MM therapy rather than\u00a0in\u00a0<\/span>the relapsed\u00a0<\/span>refractory setting,<\/span>\u00a0where their use is currently approved.<\/p>\n

Teclistamab responders also had lower\u00a0<\/span><\/span><\/span><\/span><\/span>sBCMA<\/span>\u00a0<\/span><\/span>concentrations,<\/span>\u00a0and elevated sBCMA (but not surface BCMA) was associated with worse disease (high-risk\u00a0<\/span>International Staging System scores<\/span><\/span>\u00a0<\/span>and extramedullary involvement) and with a greater\u00a0bone marrow\u00a0PC<\/span><\/span>\u00a0<\/span>cellularity.52<\/sup><\/span>\u00a0These features were associated with more baseline T\u00a0<\/span>cell dysfunction,<\/span>\u00a0and likely account for the lower response\u00a0rates\u00a0<\/span>in patients with high tumou<\/span>r burden. Again, these findings challenge the current treatment paradigm and suggest the use of teclistamab in maintenance\u00a0<\/span><\/span><\/span>or other low-disease-burden setting, as investigated in the MajesTEC-4, MASTER-2 and Immuno-PRISM trials, may allow for long-lasting<\/span><\/span>\u00a0anti-tumou<\/span>r immunity\u00a0(<\/span><\/span>Table 1<\/span><\/span><\/span><\/span>)<\/span>.1,51,60\u201371<\/sup><\/span><\/p>\n

\"\"<\/p>\n

\"\"<\/p>\n

Lastly, a\u00a0<\/span>preclinical<\/span>\u00a0study\u00a0<\/span>found that pretreatment\u00a0with\u00a0<\/span>CD38 inhibition enhanced teclistamab activity in a synergistic manner, possibly due to the immunomodulatory\u00a0effect\u00a0<\/span>of daratumumab in the tumou<\/span>r microenvironment,<\/span>72\u201376<\/sup><\/span><\/span>\u00a0and its inhibition of\u00a0<\/span>nico<\/span>tinamide\u00a0<\/span>adenine dinucleotidase\u00a0<\/span>activity<\/span>, which, in turn, may avert T\u00a0<\/span>cell exhaustion.<\/span>40,77<\/sup><\/span>\u00a0Daratumumab-lenalidomide synergism has been previously demonstrated.<\/span><\/span>78<\/sup><\/span>\u00a0As such, various teclistamab-containing multi–<\/span>drug regimens are currently under investigation in newly diagnosed (MajesTEC<\/span>-4,65<\/sup><\/span>\u00a0MajesTEC<\/span>-7\u00a0[ClinicalTrials.gov identifier:\u00a0NCT0555222268<\/sup><\/span>]<\/span><\/span><\/span>\u00a0and<\/span>\u00a0MASTER-2\u00a0[ClinicalTrials.gov identifier:\u00a0<\/span>NCT05231629]<\/span>64<\/sup><\/span><\/span><\/span>), early (MajesTEC<\/span>-3\u00a0[ClinicalTrials.gov identifier:\u00a0<\/span>NCT05083169]<\/span>63<\/sup><\/span>\u00a0<\/span>and\u00a0<\/span>MajesTEC<\/span>-9\u00a0[ClinicalTrials.gov identifier:\u00a0<\/span>NCT05572515]<\/span>69<\/sup><\/span><\/span><\/span>) and late relapsed settings (TRIMM-3\u00a0<\/span>[ClinicalTrials.gov identifier:\u00a0<\/span>NCT05338775]66<\/sup><\/span><\/span>\u00a0<\/span>and\u00a0<\/span><\/span>RedirecTT-1\u00a0[ClinicalTrials.gov identifier:\u00a0<\/span>NCT04586426]60<\/sup><\/span><\/span><\/b><\/span><\/span>)\u00a0<\/span>(Table 1<\/span>). How and when these combinations are adopted will largely depend on the safety of the regimen and whether the\u00a0progression-free and overall survival\u00a0<\/span>advantages<\/span>\u00a0outweigh the risk of incremental toxicity. For example, recently presented early results from\u00a0<\/span><\/span>MajesTEC-2<\/span><\/span>\u00a0combining teclistamab with lenalidomide and daratumumab in\u00a0patients with\u00a0<\/span>RRMM who had received\u00a01\u2013<\/span><\/span><\/span>3<\/span>\u00a0prior lines of therapy was highly efficacious but again associated with a high rate of infectious complications.61<\/sup><\/span>\u00a0In these early lines of therapy, responses are expected to be very durable, which would expose patients to cumulative immune suppression. Alternative dosing strategies in which teclistamab is administered for fixed durations, with intermittent re-dosing upon disease progression, may be important for safe use in early lines\u00a0<\/span>of\u00a0<\/span>therapy. Such intermittent dosing may also improve efficacy by alleviating T\u00a0<\/span>cell exhaustion associated with continuous administration.79<\/sup><\/span><\/p>\n

Treatment paradigms and discussion<\/h1>\n

TCE therapies for MM have evolved rapidly.\u00a0<\/span>Though\u00a0CAR T<\/span>\u00a0cells demonstrated the most impressive single-agent response rates ever reported in RRMM just a couple\u00a0of\u00a0<\/span>years ago<\/span>, teclistamab now enables similar efficacy but with off-the-shelf availability and subcutaneous administration.9,11<\/sup><\/span>\u00a0B<\/span>oth\u00a0CAR T<\/span>\u00a0cells and BsAb\u00a0therapy continue to innovate<\/span>. For example, abbreviated manufacturing protocols may improve both\u00a0the<\/span>\u00a0efficacy and accessibility of\u00a0CAR T<\/span>\u00a0cell therapy,80<\/sup><\/span>\u00a0and trispecific antibodies that enable dual-antigen specificity or\u00a0that\u00a0<\/span>incorporate\u00a0<\/span>costimulatory or checkpoint-blocking domains\u00a0are in development<\/span><\/span>.81<\/sup><\/span>\u00a0Collectively, these are paradigm-shifting advances with\u00a0the\u00a0<\/span>potential to add years to the survival of the typical patient\u00a0with MM<\/span>.<\/p>\n

We do not yet\u00a0know how<\/span>\u00a0best to\u00a0<\/span>use\u00a0<\/span>these agents in practice.<\/span>\u00a0<\/span>Both\u00a0CAR T<\/span>\u00a0cells and teclistamab are currently approved for patients with at least\u00a0four<\/span>\u00a0prior lines of MM therapy<\/span><\/span>;<\/span>\u00a0however,<\/span>\u00a0al<\/span>l<\/span>\u00a0these agents are being evaluated in earlier lines of MM therapy\u00a0(<\/span><\/span>Table 1<\/span>)<\/span><\/span>.8,10,12<\/sup><\/span>\u00a0Meanwhile, non-TCE therapies continue\u00a0to progress<\/span>, notably with molecules such as<\/span>\u00a0iberdomide82<\/sup><\/span>\u00a0and mezigdomide<\/span>,83<\/sup><\/span>\u00a0which build on lenalidomide\u2019s mechanism of action, and novel immunotherapies such as modakafusp alfa, an anti-CD38 antibody-cytokine fusion protein.84<\/sup><\/span>\u00a0Extensive clinical investigation will be required to determine how to best sequence and combine these agents with current therapies; such studies will hopefully incorporate correlative studies to inform personalized treatment approaches.<\/p>\n

Though it is tempting to contrast different TCE therapies, patients can receive both BsAb and\u00a0CAR T<\/span>\u00a0cells sequentially. Teclistamab has been prospectively evaluated in a small cohort of patients previously treated with anti-BCMA\u00a0CAR T<\/span>\u00a0cells or the anti-BCMA antibody\u2013<\/span>drug conjugate belantamab mafadotin; the response rate\u00a0in these patients\u00a0<\/span>was only slightly lower\u00a0than<\/span>\u00a0in patients who were nai<\/span>ve to BCMA-directed therapy.85<\/sup><\/span>\u00a0Similarly,\u00a0ciltacabtagene autoleucel<\/span>\u00a0has been prospectively studied after prior BCMA-directed therapy with promising results,<\/span>86<\/sup><\/span>\u00a0and several retrospective reports have demonstrated efficacy with sequential BCMA-directed therapies<\/span><\/span>.87\u201389<\/sup><\/span><\/p>\n

Although BCMA-negative relapses have been reported,90<\/sup><\/span>\u00a0most cases of progression after anti-BCMA\u00a0CAR T<\/span>\u00a0cells do not appear related to antigenic escape.91<\/sup><\/span>\u00a0Continuously dosed BsAbs<\/span>\u00a0likely exert more durable target-directed immune surveillance than\u00a0CAR T<\/span>\u00a0cells, which wane after several months in most RRMM patients.<\/span>9,11<\/sup><\/span>\u00a0Target-negative relapse may,<\/span>\u00a0therefore,<\/span>\u00a0be more likely after BsAb therapy than\u00a0CAR T<\/span>\u00a0cell therapy;<\/span>\u00a0however,<\/span>\u00a0this has not yet been evaluated. Patients progressing after BCMA-directed TCE\u00a0therapy<\/span>\u00a0have been shown to respond to both BsAb and\u00a0CAR T<\/span>\u00a0cells directed against\u00a0<\/span><\/span><\/span>GPRC5D<\/span><\/span><\/span><\/span>.43,92,93<\/sup><\/span><\/p>\n

Our current approach to sequencing teclistamab and\u00a0CAR T<\/span>\u00a0cells is driven by patient-specific factors, including patient preference either\u00a0for\u00a0<\/span>a single–<\/span>dose,<\/span>\u00a0but more complex,<\/span>\u00a0CAR T<\/span>\u00a0cell approach or for the simpler,<\/span>\u00a0but continuously dosed,<\/span>\u00a0teclistamab. Patients with rapidly progressive RRMM now have teclistamab as a readily available option.\u00a0However,\u00a0<\/span>t<\/span>eclistamab may still be preferred for patients with gradual and uncomplicated progression,<\/span>\u00a0depending on\u00a0the<\/span>\u00a0accessibility of a cellular therapy centre<\/span>\u00a0and patient tolerance of\u00a0CAR T<\/span>\u00a0cell toxicities and logistical requirements.<\/p>\n

Finally, with all this exciting progress, we must not lose sight of the stubbornly high propensity for relapse that remains even after treatment with these potent novel therapies and of the high cost required to sustain years of sophisticated therapy in patients\u00a0with MM<\/span>. More focused research is required on the specific mechanisms of relapse and the biology of resistant disease that persists, often below detectable limits, and that presumably seeds future relapses. In addition,\u00a0a\u00a0<\/span>nuanced clinical and translational investigation is required to understand when and for whom continuous therapy promotes long-term survival compared\u00a0with<\/span>\u00a0more intermittent therapy.<\/p>\n","protected":false},"excerpt":{"rendered":"

Multiple myeloma\u00a0(MM) is the\u00a0second most common\u00a0haematological malignancy,\u00a0with upwards of\u00a035,000\u00a0diagnoses in the USA\u00a0each year.1,2\u00a0It remains a leading cause of blood cancer–related mortality\u00a0worldwide,\u00a0and although therapeutic advances have allowed for significant improvements in the median overall survival,3,4\u00a0the majority of patients still experience cycles of relapse that are eventually fatal.5\u00a0While\u00a0patients\u00a0with MM\u00a0are living longer,\u00a0a subgroup with\u00a0high-risk disease\u00a0at diagnosis\u00a0still does\u00a0poorly, with\u00a0a\u00a0median […]<\/p>\n","protected":false},"author":100366,"featured_media":46865,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","rank_math_lock_modified_date":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-71222","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","vocabulary_1-haematological-malignancies","vocabulary_1-multiple-myeloma","journal-touchreviews-in-oncology-haematology"],"acf":{"wpcf-article_introduction":"","wpcf-article_abstract":"Several new drugs and regimens have greatly improved outcomes in\u00a0multiple myeloma<\/span>, but the rapid emergence of new targets and immune-based modalities has added significant complexity to the management of\u00a0relapsed\u00a0and\u00a0<\/span>refractory multiple myeloma<\/span>\u00a0(RRMM<\/span>). Teclistamab is a T\u00a0<\/span>cell-redirecting anti-CD3\u00a0\u00d7<\/span>\u00a0anti-B cell maturation antigen<\/span>\u00a0bispecific antibody\u00a0recently approved as monotherapy against RRMM<\/span><\/span>.\u00a0<\/span>The drug is now the fourth\u00a0B cell maturation antigen<\/span>-targeting agent commercially used in RRMM and the third different drug class and mechanism of action doing so.\u00a0<\/span>Although approved as a\u00a0single\u00a0<\/span>agent in relapsed and refractory disease,<\/span>\u00a0preclinical<\/span>\u00a0and clinical evidence has supported teclistamab-based regimens for use in earlier<\/span>\u00a0<\/span>lines<\/span>\u00a0or in combination strategies. The identification of novel suitable cell-surface targets in\u00a0multiple myeloma\u00a0<\/span>and the promising efficacy seen in early-<\/span>phase studies\u00a0represent\u00a0<\/span>additional innovations to the treatment paradigms for RRMM.","wpcf-article_keywords":"Anti-CD3 x anti-BCMA bispecific antibody, <\/span>bispecific antibody, <\/span>multiple myeloma, <\/span>relapsed and refractory multiple myeloma, <\/span>teclistamab, <\/span>T cell engaging therapies<\/span>","wpcf-article_citation_override":"touchREVIEWS in Oncology & Haematology<\/i>. 2023;19(1):46\u201351 DOI: https:\/\/doi.org\/10.17925\/OHR.2023.19.1.46<\/a>","wpcf-compliance-with-ethics":"This article involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors.","wpcf-article_disclosure":"Alfred L Garfall receives research funding from Novartis, Janssen, CRISPR Therapeutics and Tmunity; consulting\/honoraria from Janssen, BMS, Legend Biotech and GSK; and IDMC membership for Janssen. Beatrice M Razzo has\u00a0no financial or non-financial relationships or activities to declare in relation to this article.<\/span>","wpcf-review_process":"Double-blind peer review.","wpcf-authorship":"The named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.","wpcf-article_correspondence":"Dr\u00a0Alfred L<\/span>\u00a0Garfall<\/span><\/span>,\u00a0Perelman Center for Advanced Medicine<\/span>,\u00a012-173 South Pavilion Extension, 3400 Civic Center Blvd., Philadelphia<\/span>,\u00a0PA 19104<\/span>,\u00a0USA<\/span><\/span>;\u00a0Alfred.Garfall@pennmedicine.upenn.edu<\/span>","wpcf-article_support":"No funding was received in the publication of this article.","wpcf-open_access":"This article is freely accessible at touchONCOLOGY.com. \u00a9 Touch Medical Media 2023","wpcf-article_pdf":"https:\/\/touchoncology.com\/wp-content\/uploads\/sites\/2\/2023\/04\/touchONC_19.1_pp46-52.pdf","wpcf-article_pdf-gated":true,"wpcf-article_doi":"","wpcf-old_nid":"","wpcf-article_image":"","wpcf-editor_choice":false,"wpcf-old_author_ids":"","wpcf-article_references":"

1.<\/span>\u00a0Clinicaltrials.gov. Dose escalation study of teclistamab, a humanized BCMA*CD3 bispecific antibody, in participants with relapsed or refractory multiple myeloma (majesTEC-1). ClinicalTrials.gov identifier: NCT03145181<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03145181<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

<\/span><\/span><\/span><\/span>2.<\/span>\u00a0American Cancer Society<\/span>.\u00a0Key statistics about multiple myeloma<\/span>.\u00a0Available at<\/span>:\u00a0www.cancer.org\/cancer\/multiple-myeloma\/about\/key-statistics.html<\/span><\/a>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

3.<\/span>\u00a0Kumar<\/span>\u00a0SK<\/span><\/span>,\u00a0Dispenzieri<\/span>\u00a0A<\/span><\/span>,\u00a0Lacy<\/span>\u00a0MQ<\/span><\/span>,\u00a0et al<\/span>.\u00a0Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients<\/span>.\u00a0Leukemia<\/em><\/span>.\u00a02014<\/span>;28<\/span>:1122<\/span>\u20138<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/leu.2013.313<\/span><\/p>\r\n

4.<\/span>\u00a0Turesson<\/span>\u00a0I<\/span><\/span>,\u00a0Bjorkholm<\/span>\u00a0M<\/span><\/span>,\u00a0Blimark<\/span>\u00a0CH<\/span><\/span>,\u00a0et al<\/span>.\u00a0Rapidly changing myeloma epidemiology in the general population: Increased incidence, older patients, and longer survival<\/span>.\u00a0Eur J Haematol<\/em><\/span>.\u00a02018<\/span>;101<\/span>:237<\/span>\u201344<\/span>.\u00a0DOI<\/span>:\u00a010.1111\/ejh.13083<\/span><\/p>\r\n

5.<\/span>\u00a0Ludwig<\/span>\u00a0H<\/span><\/span>,\u00a0Novis Durie<\/span>\u00a0S<\/span><\/span>,\u00a0Meckl<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0Multiple myeloma incidence and mortality around the globe; interrelations between health access and quality, economic resources, and patient empowerment<\/span>.\u00a0Oncologist<\/em><\/span>.\u00a02020<\/span>;25<\/span>:e1406<\/span>\u201313<\/span>.\u00a0DOI<\/span>:\u00a010.1634\/theoncologist.2020-0141<\/span><\/p>\r\n

<\/span><\/span>6.<\/span>\u00a0D\u2019Agostino<\/span>\u00a0M<\/span><\/span>,\u00a0Cairns<\/span>\u00a0DA<\/span><\/span>,\u00a0Lahuerta<\/span>\u00a0JJ<\/span><\/span>,\u00a0et al<\/span>.\u00a0Second revision of the international staging system (R2-ISS) for overall survival in multiple myeloma: A European Myeloma Network (EMN) report within the Harmony project<\/span>.\u00a0J Clin Oncol<\/em><\/span>.\u00a02022<\/span>;40<\/span>:3406<\/span>\u201318<\/span>.\u00a0DOI<\/span>:\u00a010.1200\/JCO.21.02614<\/span><\/p>\r\n

7.<\/span>\u00a0Gandhi<\/span>\u00a0UH<\/span><\/span>,\u00a0Cornell<\/span>\u00a0RF<\/span><\/span>,\u00a0Lakshman<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy<\/span>.\u00a0Leukemia<\/em><\/span>.\u00a02019<\/span>;33<\/span>:2266<\/span>\u201375<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/s41375-019-0435-7<\/span><\/p>\r\n

<\/span>8.<\/span>\u00a0US Food and Drug Administration<\/span>.\u00a0FDA APPROVES Idecabtagene Vicleucel for multiple myeloma<\/span>.\u00a0Available at<\/span>:\u00a0www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-idecabtagene-vicleucel-multiple-myeloma<\/span><\/a>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

9.<\/span>\u00a0Munshi<\/span>\u00a0NC<\/span><\/span>,\u00a0Anderson<\/span>\u00a0LD<\/span><\/span>\u00a0Jr\u00a0<\/span>Shah<\/span>\u00a0N<\/span><\/span>,\u00a0et al<\/span>.\u00a0Idecabtagene vicleucel in relapsed and refractory multiple myeloma<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02021<\/span>;384<\/span>:705<\/span>\u201316<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa2024850<\/span><\/p>\r\n

<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span>10.<\/span>\u00a0US Food and Drug Administration. FDA approves ciltacabtagene autoluecel for relapsed or refractory multiple myeloma<\/span>\u00a0.\u00a0Available at<\/span>:\u00a0www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-ciltacabtagene-autoleucel-relapsed-or-refractory-multiple-myeloma<\/span><\/a>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

11.<\/span>\u00a0Berdeja<\/span>\u00a0JG<\/span><\/span>,\u00a0Madduri<\/span>\u00a0D<\/span><\/span>,\u00a0Usmani<\/span>\u00a0SZ<\/span><\/span>,\u00a0et al<\/span>.\u00a0Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): A phase 1b\/2 open-label study<\/span>.\u00a0Lancet<\/em><\/span>.\u00a02021<\/span>;398<\/span>:314<\/span>\u201324<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/S0140-6736(21)00933-8<\/span><\/p>\r\n

12.<\/span>\u00a0US Food and Drug Administration. FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma<\/span>.\u00a0Available at<\/span>:\u00a0www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiple-myeloma<\/span><\/a>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

<\/span><\/span>13.<\/span>\u00a0Moreau<\/span>\u00a0P<\/span><\/span>,\u00a0Garfall<\/span>\u00a0AL<\/span><\/span>,\u00a0van de Donk<\/span>\u00a0N<\/span><\/span>,\u00a0et al<\/span>.\u00a0Teclistamab in relapsed or refractory multiple myeloma<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02022<\/span>;387<\/span>:495<\/span>\u2013505<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa2203478<\/span><\/p>\r\n

14.<\/span>\u00a0Laabi<\/span>\u00a0Y<\/span><\/span>,\u00a0Gras<\/span>\u00a0MP<\/span><\/span>,\u00a0Brouet<\/span>\u00a0JC<\/span><\/span>,\u00a0et al<\/span>.\u00a0The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed<\/span>.\u00a0Nucleic Acids Res<\/em><\/span>.\u00a01994<\/span>;22<\/span>:1147<\/span>\u201354<\/span>.\u00a0DOI<\/span>:\u00a010.1093\/nar\/22.7.1147<\/span><\/p>\r\n

15.<\/span>\u00a0Carpenter<\/span>\u00a0RO<\/span><\/span>,\u00a0Evbuomwan<\/span>\u00a0MO<\/span><\/span>,\u00a0Pittaluga<\/span>\u00a0S<\/span><\/span>,\u00a0et al<\/span>.\u00a0B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma<\/span>.\u00a0Clin Cancer Res<\/em><\/span>.\u00a02013<\/span>;19<\/span>:2048<\/span>\u201360<\/span>.\u00a0DOI<\/span>:\u00a010.1158\/1078-0432.CCR-12-2422<\/span><\/p>\r\n

16.<\/span>\u00a0Tai<\/span>\u00a0YT<\/span><\/span>,\u00a0Mayes<\/span>\u00a0PA<\/span><\/span>,\u00a0Acharya<\/span>\u00a0C<\/span><\/span>,\u00a0et al<\/span>.\u00a0Novel anti\u2013B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma<\/span>.\u00a0Blood<\/em><\/span>.\u00a02014<\/span>;123<\/span>:3128<\/span>\u201338<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2013-10-535088<\/span><\/p>\r\n

17.<\/span>\u00a0Van Oekelen<\/span>\u00a0O<\/span><\/span>,\u00a0Aleman<\/span>\u00a0A<\/span><\/span>,\u00a0Upadhyaya<\/span>\u00a0B<\/span><\/span>,\u00a0et al<\/span>.\u00a0Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy<\/span>.\u00a0Nat Med<\/em><\/span>.\u00a02021<\/span>;27<\/span>:2099<\/span>\u2013103<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/s41591-021-01564-7<\/span><\/p>\r\n

18.<\/span>\u00a0Bu<\/span>\u00a0D-X<\/span><\/span>,\u00a0Singh<\/span>\u00a0R<\/span><\/span>,\u00a0Choi<\/span>\u00a0EE<\/span><\/span>,\u00a0et al<\/span>.\u00a0Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma<\/span>.\u00a0Oncotarget<\/em><\/span>.\u00a02018<\/span>;9<\/span>:25764<\/span>\u201380<\/span>.\u00a0DOI<\/span>:\u00a010.18632\/oncotarget.25359<\/span><\/p>\r\n

19.<\/span>\u00a0Marella<\/span>\u00a0M<\/span><\/span>,\u00a0Yao<\/span>\u00a0X<\/span><\/span>,\u00a0Carreira<\/span>\u00a0V<\/span><\/span>,\u00a0et al<\/span>.\u00a0Comprehensive BCMA expression profiling in adult normal human brain suggests a low risk of on-target neurotoxicity in BCMA-targeting multiple myeloma therapy<\/span>.\u00a0J Histochem Cytochem<\/em><\/span>.\u00a02022<\/span>;70<\/span>:273<\/span>\u201387<\/span>.\u00a0DOI<\/span>:\u00a010.1369\/00221554221079579<\/span><\/p>\r\n

20.<\/span>\u00a0Eckhert<\/span>\u00a0E<\/span><\/span>,\u00a0Hewitt<\/span>\u00a0R<\/span><\/span>,\u00a0Liedtke<\/span>\u00a0M<\/span><\/span>.\u00a0B-cell maturation antigen directed monoclonal antibody therapies for multiple myeloma<\/span>.\u00a0Immunotherapy<\/em><\/span>.\u00a02019<\/span>;11<\/span>:801<\/span>\u201311<\/span>.\u00a0DOI<\/span>:\u00a010.2217\/imt-2018-0199<\/span><\/p>\r\n

21.<\/span>\u00a0Romano<\/span>\u00a0A<\/span><\/span>,\u00a0Storti<\/span>\u00a0P<\/span><\/span>,\u00a0Marchica<\/span>\u00a0V<\/span><\/span>,\u00a0et al<\/span>.\u00a0Mechanisms of action of the new antibodies in use in multiple myeloma<\/span>.\u00a0Front Oncol<\/em><\/span>.\u00a02021<\/span>;11<\/span>:684561<\/span>.\u00a0DOI<\/span>:\u00a010.3389\/fonc.2021.684561<\/span><\/p>\r\n

22.<\/span>\u00a0Peperzak<\/span>\u00a0V<\/span><\/span>,\u00a0Vikstr\u00f6m<\/span>\u00a0I<\/span><\/span>,\u00a0Walker<\/span>\u00a0J<\/span><\/span>,\u00a0et al<\/span>.\u00a0Mcl-1 is essential for the survival of plasma cells<\/span>.\u00a0Nat Immunol<\/em><\/span>.\u00a02013<\/span>;14<\/span>:290<\/span>\u20137<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/ni.2527<\/span><\/p>\r\n

23.<\/span>\u00a0Bossen<\/span>\u00a0C<\/span><\/span>,\u00a0Cachero<\/span>\u00a0TG<\/span><\/span>,\u00a0Tardivel<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and April to support survival of activated B cells and plasmablasts<\/span>.\u00a0Blood<\/em><\/span>.\u00a02008<\/span>;111<\/span>:1004<\/span>\u201312<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2007-09-110874<\/span><\/p>\r\n

24.<\/span>\u00a0Hatzoglou<\/span>\u00a0A<\/span><\/span>,\u00a0Roussel<\/span>\u00a0J<\/span><\/span>,\u00a0Bourgeade<\/span>\u00a0MF<\/span><\/span>,\u00a0et al<\/span>.\u00a0TNFnf<\/span><\/span>\u00a0receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, Elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase<\/span>.\u00a0J Immunol<\/em><\/span>.\u00a02000<\/span>;165<\/span>:1322<\/span>\u201330<\/span>.\u00a0DOI<\/span>:\u00a010.4049\/jimmunol.165.3.1322<\/span><\/p>\r\n

25.<\/span>\u00a0O\u2019Connor<\/span>\u00a0BP<\/span><\/span>,\u00a0Raman<\/span>\u00a0VS<\/span><\/span>,\u00a0Erickson<\/span>\u00a0LD<\/span><\/span>,\u00a0et al<\/span>.\u00a0BCMA is essential for the survival of long-lived bone marrow plasma cells<\/span>.\u00a0J Exp Med<\/em><\/span>.\u00a02004<\/span>;199<\/span>:91<\/span>\u20138<\/span>.\u00a0DOI<\/span>:\u00a010.1084\/jem.20031330<\/span><\/p>\r\n

26.<\/span>\u00a0Tai<\/span>\u00a0Y-T<\/span><\/span>,\u00a0Acharya<\/span>\u00a0C<\/span><\/span>,\u00a0An<\/span>\u00a0G<\/span><\/span>,\u00a0et al<\/span>.\u00a0April and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment<\/span>.\u00a0Blood<\/em><\/span>.\u00a02016<\/span>;127<\/span>:3225<\/span>\u201336<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2016-01-691162<\/span><\/p>\r\n

27.<\/span>\u00a0Castigli<\/span>\u00a0E<\/span><\/span>,\u00a0Wilson<\/span>\u00a0SA<\/span><\/span>,\u00a0Scott<\/span>\u00a0S<\/span><\/span>,\u00a0et al<\/span>.\u00a0TACI and BAFF-R mediate isotype switching in B cells<\/span>.\u00a0J Exp Med<\/em><\/span>.\u00a02005<\/span>;201<\/span>:35<\/span>\u20139<\/span>.\u00a0DOI<\/span>:\u00a010.1084\/jem.20032000<\/span><\/p>\r\n

28.<\/span>\u00a0Laurent<\/span>\u00a0SA<\/span><\/span>,\u00a0Hoffmann<\/span>\u00a0FS<\/span><\/span>,\u00a0Kuhn<\/span>\u00a0P-H<\/span><\/span>,\u00a0et al<\/span>.\u00a0\u0393-Secretase directly sheds the survival receptor BCMA from plasma cells<\/span>.\u00a0Nat Commun<\/em><\/span>.\u00a02015<\/span>;6<\/span>:7333<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/ncomms8333<\/span><\/p>\r\n

29.<\/span>\u00a0Sanchez<\/span>\u00a0E<\/span><\/span>,\u00a0Gillespie<\/span>\u00a0A<\/span><\/span>,\u00a0Tang<\/span>\u00a0G<\/span><\/span>,\u00a0et al<\/span>.\u00a0Soluble B-cell maturation antigen mediates tumor-induced immune deficiency in multiple myeloma<\/span>.\u00a0Clin Cancer Res<\/em><\/span>.\u00a02016<\/span>;22<\/span>:3383<\/span>\u201397<\/span>.\u00a0DOI<\/span>:\u00a010.1158\/1078-0432.CCR-15-2224<\/span><\/p>\r\n

30.<\/span>\u00a0Claudio<\/span>\u00a0JO<\/span><\/span>,\u00a0Masih-Khan<\/span>\u00a0E<\/span><\/span>,\u00a0Tang<\/span>\u00a0H<\/span><\/span>,\u00a0et al<\/span>.\u00a0A molecular compendium of genes expressed in multiple myeloma<\/span>.\u00a0Blood<\/em><\/span>.\u00a02002<\/span>;100<\/span>:2175<\/span>\u201386<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2002-01-0008<\/span><\/p>\r\n

31.<\/span>\u00a0Annunziata<\/span>\u00a0CM<\/span><\/span>,\u00a0Davis<\/span>\u00a0RE<\/span><\/span>,\u00a0Demchenko<\/span>\u00a0Y<\/span><\/span>,\u00a0et al<\/span>.\u00a0Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma<\/span>.\u00a0Cancer Cell<\/em><\/span>.\u00a02007<\/span>;12<\/span>:115<\/span>\u201330<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.ccr.2007.07.004<\/span><\/p>\r\n

32.<\/span>\u00a0Sanchez<\/span>\u00a0E<\/span><\/span>,\u00a0Li<\/span>\u00a0M<\/span><\/span>,\u00a0Kitto<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival<\/span>.\u00a0Br J Haematol<\/em><\/span>.\u00a02012<\/span>;158<\/span>:727<\/span>\u201338<\/span>.\u00a0DOI<\/span>:\u00a010.1111\/j.1365-2141.2012.09241.x<\/span><\/p>\r\n

33.<\/span>\u00a0Ryan<\/span>\u00a0MC<\/span><\/span>,\u00a0Hering<\/span>\u00a0M<\/span><\/span>,\u00a0Peckham<\/span>\u00a0D<\/span><\/span>,\u00a0et al<\/span>.\u00a0Antibody targeting of B-cell maturation antigen on malignant plasma cells<\/span>.\u00a0Mol Cancer Ther<\/em><\/span>.\u00a02007<\/span>;6<\/span>:3009<\/span>\u201318<\/span>.\u00a0DOI<\/span>:\u00a010.1158\/1535-7163.MCT-07-0464<\/span><\/p>\r\n

34.<\/span>\u00a0Lejeune<\/span>\u00a0M<\/span><\/span>,\u00a0K\u00f6se<\/span>\u00a0MC<\/span><\/span>,\u00a0Duray<\/span>\u00a0E<\/span><\/span>,\u00a0et al<\/span>.\u00a0Bispecific, T-cell-recruiting antibodies in B-cell malignancies<\/span>.\u00a0Front Immunol<\/em><\/span>.\u00a02020<\/span>;11<\/span>:762<\/span>.\u00a0DOI<\/span>:\u00a010.3389\/fimmu.2020.00762<\/span><\/p>\r\n

35.<\/span>\u00a0Perez<\/span>\u00a0P<\/span><\/span>,\u00a0Hoffman<\/span>\u00a0RW<\/span><\/span>,\u00a0Shaw<\/span>\u00a0S<\/span><\/span>,\u00a0et al<\/span>.\u00a0Specific targeting of cytotoxic T cells by anti-T3 linked to anti-target cell antibody<\/span>.\u00a0Nature<\/em><\/span>.\u00a01985<\/span>;316<\/span>:354<\/span>\u20136<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/316354a0<\/span><\/p>\r\n

36.<\/span>\u00a0De Gast<\/span>\u00a0GC<\/span><\/span>,\u00a0Van Houten<\/span>\u00a0AA<\/span><\/span>,\u00a0Haagen<\/span>\u00a0IA<\/span><\/span>,\u00a0et al<\/span>.\u00a0Clinical experience with CD3 x CD19 bispecific antibodies in patients with B cell malignancies<\/span>.\u00a0J Hematother<\/em><\/span>.\u00a01995<\/span>;4<\/span>:433<\/span>\u20137<\/span>.\u00a0DOI<\/span>:\u00a010.1089\/scd.1.1995.4.433<\/span><\/p>\r\n

37.<\/span>\u00a0Kantarjian<\/span>\u00a0H<\/span><\/span>,\u00a0Stein<\/span>\u00a0A<\/span><\/span>,\u00a0G\u00f6kbuget<\/span>\u00a0N<\/span><\/span>,\u00a0et al<\/span>.\u00a0Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02017<\/span>;376<\/span>:836<\/span>\u201347<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa1609783<\/span><\/p>\r\n

38.<\/span>\u00a0Hipp<\/span>\u00a0S<\/span><\/span>,\u00a0Tai<\/span>\u00a0Y-T<\/span><\/span>,\u00a0Blanset<\/span>\u00a0D<\/span><\/span>,\u00a0et al<\/span>.\u00a0A novel BCMA\/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo<\/span>.\u00a0Leukemia<\/em><\/span>.\u00a02017<\/span>;31<\/span>:2278<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/leu.2017.219<\/span><\/p>\r\n

39.<\/span>\u00a0Topp<\/span>\u00a0MS<\/span><\/span>,\u00a0Duell<\/span>\u00a0J<\/span><\/span>,\u00a0Zugmaier<\/span>\u00a0G<\/span><\/span>,\u00a0et al<\/span>.\u00a0Anti-B-cell maturation antigen bite molecule AMG 420 induces responses in multiple myeloma<\/span>.\u00a0J Clin Oncol<\/em><\/span>.\u00a02020<\/span>;38<\/span>:775<\/span>\u201383<\/span>.\u00a0DOI<\/span>:\u00a010.1200\/JCO.19.02657<\/span><\/p>\r\n

40.<\/span>\u00a0Verkleij<\/span>\u00a0CPM<\/span><\/span>,\u00a0Frerichs<\/span>\u00a0KA<\/span><\/span>,\u00a0Broekmans<\/span>\u00a0M<\/span><\/span>,\u00a0et al<\/span>.\u00a0T-cell redirecting bispecific antibodies targeting BCMA for the treatment of multiple myeloma<\/span>.\u00a0Oncotarget<\/em><\/span>.\u00a02020<\/span>;11<\/span>:4076<\/span>\u201381<\/span>.\u00a0DOI<\/span>:\u00a010.18632\/oncotarget.27792<\/span><\/p>\r\n

41.<\/span>\u00a0Moreau<\/span>\u00a0P<\/span><\/span>,\u00a0Touzeau<\/span>\u00a0C<\/span><\/span>.\u00a0T-cell-redirecting bispecific antibodies in multiple myeloma: A revolution?<\/span>\u00a0Blood<\/em><\/span>.\u00a02022<\/span>;139<\/span>:3681<\/span>\u20137<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood.2021014611<\/span><\/p>\r\n

42.<\/span>\u00a0ClinicalTrials.gov. Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma (MonumenTAL-1)<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03399799<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

<\/span>43.<\/span>\u00a0Chari<\/span>\u00a0A<\/span><\/span>,\u00a0Minnema<\/span>\u00a0MC<\/span><\/span>,\u00a0Berdeja<\/span>\u00a0JG<\/span><\/span>,\u00a0et al<\/span>.\u00a0Talquetamab, a T-cell\u2013redirecting GPRC5D bispecific antibody for multiple myeloma<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02022<\/span>;387<\/span>:2232<\/span>\u201344<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMoa2204591<\/span><\/p>\r\n

44.<\/span>\u00a0ClinicalTrials.gov. A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04108195<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

45.<\/span>\u00a0Cohen<\/span>\u00a0YC<\/span><\/span>,\u00a0Moreau<\/span>\u00a0P<\/span><\/span>,\u00a0Tolbert<\/span>\u00a0J<\/span><\/span>,\u00a0et al<\/span>.\u00a0MonumenTAL-3: phase 3 trial of talquetamab + daratumumab \u00b1 pomalidomide versus daratumumab + pomalidomide + dexamethasone in relapsed\/refractory multiple myeloma following \u22651 prior line of therapy<\/span>.\u00a0Blood<\/em><\/span>.\u00a02022<\/span>;140<\/span>:4418<\/span>\u20139<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2022-162733<\/span><\/p>\r\n

46.<\/span>\u00a0ClinicalTrials.gov. A Study of Talquetamab With Other Anticancer Therapies in Participants With Multiple Myeloma (MonumenTAL-2)<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05050097<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

47.<\/span>\u00a0Trudel<\/span>\u00a0S<\/span><\/span>,\u00a0Cohen<\/span>\u00a0AD<\/span><\/span>,\u00a0Krishnan<\/span>\u00a0AY<\/span><\/span>,\u00a0et al<\/span>.\u00a0Cevostamab monotherapy continues to show clinically meaningful activity and manageable safety in patients with heavily pre-treated relapsed\/refractory multiple myeloma (RRMM):\u00a0Uu<\/span><\/span>pdated results from an ongoing phase I study<\/span>.\u00a0Blood<\/em><\/span>.\u00a02021<\/span>;138<\/span>:157<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2021-147983<\/span><\/p>\r\n

48.<\/span>\u00a0Pillarisetti<\/span>\u00a0K<\/span><\/span>,\u00a0Baldwin<\/span>\u00a0E<\/span><\/span>,\u00a0Babich<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0Development of a new\u00a0BCMA<\/span>xCD3<\/span>\u00a0DuoBody\u00ae antibody for multiple myeloma<\/span>.\u00a0Blood<\/em><\/span>.\u00a02016<\/span>;128<\/span>:2116<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood.V128.22.2116.2116<\/span><\/p>\r\n

49.<\/span>\u00a0Pillarisetti<\/span>\u00a0K<\/span><\/span>,\u00a0Powers<\/span>\u00a0G<\/span><\/span>,\u00a0Luistro<\/span>\u00a0L<\/span><\/span>,\u00a0et al<\/span>.\u00a0Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma<\/span>.\u00a0Blood Adv<\/em><\/span>.\u00a02020<\/span>;4<\/span>:4538<\/span>\u201349<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/bloodadvances.2020002393<\/span><\/p>\r\n

50.<\/span>\u00a0Usmani<\/span>\u00a0SZ<\/span><\/span>,\u00a0Garfall<\/span>\u00a0AL<\/span><\/span>,\u00a0van de Donk<\/span>\u00a0NWCJ<\/span><\/span>,\u00a0et al<\/span>.\u00a0Teclistamab, a B-cell maturation antigen \u00d7 CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (majesTEC-1):\u00a0A<\/span>\u00a0multicentre, open-label, single-arm, phase 1 study<\/span>.\u00a0Lancet<\/em><\/span>.\u00a02021<\/span>;398<\/span>:665<\/span>\u201374<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/S0140-6736(21)01338-6<\/span><\/p>\r\n

51.<\/span>\u00a0ClinicalTrials.gov. A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1). ClinicalTrials.gov Identifier: NCT04557098<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04557098<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

52.<\/span>\u00a0Cortes-Selva<\/span>\u00a0D<\/span><\/span>,\u00a0Casneuf<\/span>\u00a0T<\/span><\/span>,\u00a0Vishwamitra<\/span>\u00a0D<\/span><\/span>,\u00a0et al<\/span>.\u00a0Teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed\/refractory multiple myeloma (RRMM): Correlative analyses from majesTEC-1<\/span>.\u00a0Blood<\/em><\/span>.\u00a02022<\/span>;140<\/span>:241<\/span>\u20133<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2022-162709<\/span><\/p>\r\n

53. <\/span>US Food and Drug Administration <\/span><\/span><\/span>TECVAYLI highlights of Prescribing information<\/span>.\u00a0Available at<\/span>:\u00a0www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/761291s000lbl.pdf<\/span><\/a>\u00a0(Date last accessed<\/span>:\u00a021<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

54.<\/span>\u00a0Food and drug administration<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/www.google.com\/search?q=teclistamab+prescribing+information&rlz=1C1CHBF_enGB869GB869&oq=teclistamab+prescribing+information&aqs=chrome..69i57j0i22i30.3382j0j7&sourceid=chrome&ie=UTF-8&bshm=bshwcqp\/1<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a026<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

55.<\/span>\u00a0Aleman<\/span>\u00a0A<\/span><\/span>,\u00a0Upadhyaya<\/span>\u00a0B<\/span><\/span>,\u00a0Tuballes<\/span>\u00a0K<\/span><\/span>,\u00a0et al<\/span>.\u00a0Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma<\/span>.\u00a0Cancer Cell<\/em><\/span>.\u00a02021<\/span>;39<\/span>:1442<\/span>\u20134<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.ccell.2021.09.015<\/span><\/p>\r\n

56.<\/span>\u00a0Frerichs<\/span>\u00a0KA<\/span><\/span>,\u00a0Broekmans<\/span>\u00a0MEC<\/span><\/span>,\u00a0Marin Soto<\/span>\u00a0JA<\/span><\/span>,\u00a0et al<\/span>.\u00a0Preclinical activity of JNJ-7957, a novel\u00a0BCMA\u00d7CDbcma\u00d7cd<\/span><\/span>3 bispecific antibody for the treatment of multiple myeloma, is potentiated by daratumumab<\/span>.\u00a0Clin Cancer Res<\/em><\/span>.\u00a02020<\/span>;26<\/span>:2203<\/span>\u201315<\/span>.\u00a0DOI<\/span>:\u00a010.1158\/1078-0432.CCR-19-2299<\/span><\/p>\r\n

<\/span>57.<\/span>\u00a0Cohen<\/span>\u00a0AD<\/span><\/span>,\u00a0Garfall<\/span>\u00a0AL<\/span><\/span>,\u00a0Stadtmauer<\/span>\u00a0EA<\/span><\/span>,\u00a0et al<\/span>.\u00a0B cell maturation antigen\u2013specific CAR T cells are clinically active in multiple myeloma<\/span>.\u00a0J Clin Invest<\/em><\/span>.\u00a02019<\/span>;129<\/span>:2210<\/span>\u201321<\/span>.\u00a0DOI<\/span>:\u00a010.1172\/JCI126397<\/span><\/p>\r\n

<\/span><\/span>58.<\/span>\u00a0Garfall<\/span>\u00a0AL<\/span><\/span>,\u00a0Dancy<\/span>\u00a0EK<\/span><\/span>,\u00a0Cohen<\/span>\u00a0AD<\/span><\/span>,\u00a0et al<\/span>.\u00a0T-cell phenotypes associated with effective CAR T-cell therapy in postinduction vs relapsed multiple myeloma<\/span>.\u00a0Blood Adv<\/em><\/span>.\u00a02019<\/span>;3<\/span>:2812<\/span>\u20135<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/bloodadvances.2019000600<\/span><\/p>\r\n

59.<\/span>\u00a0Leblay<\/span>\u00a0N<\/span><\/span>,\u00a0Maity<\/span>\u00a0R<\/span><\/span>,\u00a0Barakat<\/span>\u00a0E<\/span><\/span>,\u00a0et al<\/span>.\u00a0Cite-seq profiling of T cells in multiple myeloma patients undergoing BCMA targeting CAR-T or bites immunotherapy<\/span>.\u00a0Blood<\/em><\/span>.\u00a02020<\/span>;136<\/span>:11<\/span>\u20132<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2020-137650<\/span><\/p>\r\n

60.<\/span>\u00a0ClinicalTrials.gov. A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (RedirecTT-1). ClinicalTrials.gov Identifier: NCT04586426<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04586426<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

61.<\/span>\u00a0Searle<\/span>\u00a0E<\/span><\/span>,\u00a0Quach<\/span>\u00a0H<\/span><\/span>,\u00a0Wong<\/span>\u00a0SW<\/span><\/span>,\u00a0et al<\/span>.\u00a0Teclistamab in combination with subcutaneous daratumumab and lenalidomide in patients with multiple myeloma:\u00a0R<\/span>esults from one cohort of majesTEC-2, a phase1b, multicohort study<\/span>.\u00a0Blood<\/em><\/span>.\u00a02022<\/span>;140<\/span>:394<\/span>\u20136<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2022-159711<\/span><\/p>\r\n

62.<\/span>\u00a0ClinicalTrials.gov. A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (RedirecTT-1). ClinicalTrials.gov Identifier: NCT04722146<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04722146<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

63.<\/span>\u00a0ClinicalTrials.gov. Study of Teclistamab in Combination With Daratumumab Subcutaneously (SC) (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-3). ClinicalTrials.gov Identifier: NCT05083169<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05083169<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

64.<\/span>\u00a0ClinicalTrials.gov. A Sequential Therapy in Multiple Myeloma Guided by MRD Assessments (MASTER-2). ClinicalTrials.gov Identifier: NCT05231629<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05231629<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

65.<\/span>\u00a0ClinicalTrials.gov. Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation (MajesTEC-4). ClinicalTrials.gov Identifier: NCT05243797<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05243797<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

66.<\/span>\u00a0ClinicalTrials.gov. A Study of Talquetamab and Teclistamab Each in Combination With a Programmed Cell Death Receptor-1 (PD-1) Inhibitor for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma (TRIMM-3). ClinicalTrials.gov Identifier: NCT05338775<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05338775<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

67.<\/span>\u00a0ClinicalTrials.gov. Immuno-PRISM (PRecision Intervention Smoldering Myeloma). ClinicalTrials.gov Identifier: NCT05469893<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05469893<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

68.<\/span>\u00a0ClinicalTrials.gov. A Study to Compare Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) in Participants With Newly Diagnosed Multiple Myeloma (MajesTEC-7). ClinicaltTials.gov Identifier: NCT05552222<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05552222<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

69.<\/span>\u00a0ClinicalTrials.gov. A Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-9). ClinicalTrials.gov Identifier: NCT05572515<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05572515<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

70.<\/span>\u00a0ClinicalTrials.gov. Study of Teclistamab in Combination in Elderly Patients With Multiple Myeloma (IFM 2021-01). ClinicalTrials.gov Identifier: NCT05572229<\/span>. .\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05572229<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

71.<\/span>\u00a0ClinicalTrials.gov. GMMG-HD10 \/ DSMM-XX \/ 64007957MMY2003, MajesTEC-5 (HD10\/DSMMXX). ClinicalTrials.gov Identifier: NCT05695508<\/span>.\u00a0Available at<\/span>:\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05695508<\/a><\/span>\u00a0(Date last accessed<\/span>:\u00a012<\/span>\u00a0April<\/span>\u00a02023<\/span>)<\/p>\r\n

<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span>72.<\/span>\u00a0Adams<\/span>\u00a0H<\/span><\/span>,\u00a0Van der Borght<\/span>\u00a0K<\/span><\/span>,\u00a0Abraham<\/span>\u00a0Y<\/span><\/span>,\u00a0et al<\/span>.\u00a0Effects of daratumumab on the composition and activation status of immune-cell populations in Centaurus, a phase 2 randomized study of smoldering multiple myeloma (SMM) patients<\/span>.\u00a0Presented at: EHA 2018, Stockholm, Sweden, 14-17 June 2018. S1577<\/span>.<\/p>\r\n

73.<\/span>\u00a0Adams<\/span>\u00a0HC<\/span>\u00a0III<\/span><\/span>,\u00a0Stevenaert<\/span>\u00a0F<\/span><\/span>,\u00a0Krejcik<\/span>\u00a0J<\/span><\/span>,\u00a0et al<\/span>.\u00a0High\u2010parameter mass cytometry evaluation of relapsed\/refractory multiple myeloma patients treated with daratumumab demonstrates immune modulation as a novel mechanism of action<\/span>.\u00a0Cytometry<\/em><\/span>.\u00a02019<\/span>;95<\/span>:279<\/span>\u201389<\/span>.\u00a0DOI<\/span>:\u00a010.1002\/cyto.a.23693<\/span><\/p>\r\n

74.<\/span>\u00a0Krejcik<\/span>\u00a0J<\/span><\/span>,\u00a0Casneuf<\/span>\u00a0T<\/span><\/span>,\u00a0Nijhof<\/span>\u00a0IS<\/span><\/span>,\u00a0et al<\/span>.\u00a0Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma<\/span>.\u00a0Blood<\/em><\/span>.\u00a02016<\/span>;128<\/span>:384<\/span>\u201394<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2015-12-687749<\/span><\/p>\r\n

<\/span>75.<\/span>\u00a0van de Donk<\/span>\u00a0NWCJ<\/span><\/span>.\u00a0Immunomodulatory effects of CD38-targeting antibodies<\/span>.\u00a0Immunol Lett<\/em><\/span>.\u00a02018<\/span>;199<\/span>:16<\/span>\u201322<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.imlet.2018.04.005<\/span><\/p>\r\n

76.<\/span>\u00a0Van De Donk<\/span>\u00a0NW<\/span><\/span>,\u00a0Adams<\/span>\u00a0H<\/span><\/span>,\u00a0Vanhoof<\/span>\u00a0G<\/span><\/span>,\u00a0et al<\/span>.\u00a0Daratumumab in combination with lenalidomide plus dexamethasone results in persistent natural killer (NK) cells with a distinct phenotype and expansion of effector memory T-cells in pollux, a phase 3 randomized study<\/span>.\u00a0Blood<\/em><\/span>.\u00a02017<\/span>;130<\/span>:3124<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood.V130.Suppl_1.3124.3124<\/span><\/p>\r\n

77.<\/span>\u00a0Chatterjee<\/span>\u00a0S<\/span><\/span>,\u00a0Daenthanasanmak<\/span>\u00a0A<\/span><\/span>,\u00a0Chakraborty<\/span>\u00a0P<\/span><\/span>,\u00a0et al<\/span>.\u00a0CD38-NAD+<\/sup>\u00a0axis regulates immunotherapeutic anti-tumor T cell response<\/span>.\u00a0Cell Metab<\/em><\/span>.\u00a02018<\/span>;27<\/span>:85<\/span>\u2013100<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/j.cmet.2017.10.006<\/span><\/p>\r\n

<\/span>78.<\/span>\u00a0van der Veer<\/span>\u00a0MS<\/span><\/span>,\u00a0de Weers<\/span>\u00a0M<\/span><\/span>,\u00a0van Kessel<\/span>\u00a0B<\/span><\/span>,\u00a0et al<\/span>.\u00a0Towards effective immunotherapy of myeloma:\u00a0Ee<\/span><\/span>nhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab<\/span>.\u00a0Haematologica<\/em><\/span>.\u00a02011<\/span>;96<\/span>:284<\/span>\u201390<\/span>.\u00a0DOI<\/span>:\u00a010.3324\/haematol.2010.030759<\/span><\/p>\r\n

79.<\/span>\u00a0Philipp<\/span>\u00a0N<\/span><\/span>,\u00a0Kazerani<\/span>\u00a0M<\/span><\/span>,\u00a0Nicholls<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals<\/span>.\u00a0Blood<\/em><\/span>.\u00a02022<\/span>;140<\/span>:1104<\/span>\u201318<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood.2022015956<\/span><\/p>\r\n

80.<\/span>\u00a0Costa<\/span>\u00a0LJ<\/span><\/span>,\u00a0Kumar<\/span>\u00a0SK<\/span><\/span>,\u00a0Atrash<\/span>\u00a0S<\/span><\/span>,\u00a0et al<\/span>.\u00a0Results from the first phase 1 clinical study of the B-cell maturation antigen (BCMA) nex T chimeric antigen receptor (CAR) T cell therapy CC-98633\/BMS-986354 in patients (pts) with relapsed\/refractory multiple myeloma (RRMM)<\/span>.\u00a0Blood<\/em><\/span>.\u00a02022<\/span>;140<\/span>:1360<\/span>\u20132<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2022-160038<\/span><\/p>\r\n

81.<\/span>\u00a0Garfall<\/span>\u00a0AL<\/span><\/span>,\u00a0June<\/span>\u00a0CH<\/span><\/span>.\u00a0Trispecific antibodies offer a third way forward for anticancer immunotherapy<\/span>.\u00a0Nature<\/em><\/span>.\u00a02019<\/span>;575<\/span>:450<\/span>\u20131<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/d41586-019-03495-3<\/span><\/p>\r\n

82.<\/span>\u00a0Lonial<\/span>\u00a0S<\/span><\/span>,\u00a0Popat<\/span>\u00a0R<\/span><\/span>,\u00a0Hulin<\/span>\u00a0C<\/span><\/span>,\u00a0et al<\/span>.\u00a0Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): A multicentre, multicohort, open-label, phase 1\/2 trial<\/span>.\u00a0Lancet Haematol<\/em><\/span>.\u00a02022<\/span>;9<\/span>:e822<\/span>\u201332<\/span>.\u00a0DOI<\/span>:\u00a010.1016\/S2352-3026(22)00290-3<\/span><\/p>\r\n

83.<\/span>\u00a0Richardson<\/span>\u00a0PG<\/span><\/span>,\u00a0Trudel<\/span>\u00a0S<\/span><\/span>,\u00a0Quach<\/span>\u00a0H<\/span><\/span>,\u00a0et al<\/span>.\u00a0Mezigdomide (CC-92480), a potent, novel cereblon E3 ligase modulator (CELMoD), combined with dexamethasone (DEX) in patients (pts) with relapsed\/refractory multiple myeloma (RRMM): Preliminary results from the dose-expansion phase of the CC-92480-MM-001 trial<\/span>.\u00a0Blood<\/em><\/span>.\u00a02022<\/span>;140<\/span>:1366<\/span>\u20138<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2022-157945<\/span><\/p>\r\n

84.<\/span>\u00a0Vogl<\/span>\u00a0DT<\/span><\/span>,\u00a0Atrash<\/span>\u00a0S<\/span><\/span>,\u00a0Holstein<\/span>\u00a0SA<\/span><\/span>,\u00a0et al<\/span>.\u00a0Final results from the first-in-human phase 1\/2 study of modakafusp alfa, an immune-targeting attenuated cytokine, in patients (pts<\/span>) with relapsed\/refractory multiple myeloma (RRMM)<\/span>.\u00a0Blood<\/em><\/span>.\u00a02022<\/span>;140<\/span>:1357<\/span>\u20139<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood-2022-162253<\/span><\/p>\r\n

85.<\/span>\u00a0Touzeau<\/span>\u00a0C<\/span><\/span>,\u00a0Krishnan<\/span>\u00a0AY<\/span><\/span>,\u00a0Moreau<\/span>\u00a0P<\/span><\/span>,\u00a0et al<\/span>.\u00a0Efficacy and safety of teclistamab (tec), a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients (pts) with relapsed\/refractory multiple myeloma (RRMM) after exposure to other BCMA-targeted agents<\/span>.\u00a0J Clin Oncol<\/em><\/span>.\u00a02022<\/span>;40<\/span>:8013<\/span>.\u00a0DOI<\/span>:\u00a010.1200\/JCO.2022.40.16_suppl.8013<\/span><\/p>\r\n

86.<\/span>\u00a0Cohen<\/span>\u00a0AD<\/span><\/span>,\u00a0Mateos<\/span>\u00a0M-V<\/span><\/span>,\u00a0Cohen<\/span>\u00a0YC<\/span><\/span>,\u00a0et al<\/span>.\u00a0Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents<\/span>.\u00a0Blood<\/em><\/span>.\u00a02023<\/span>;141<\/span>:219<\/span>\u201330<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood.2022015526<\/span><\/p>\r\n

87.<\/span>\u00a0Oliver Van Oekelen<\/span>\u00a0KN<\/span><\/span>,\u00a0Tarek<\/span>\u00a0HM<\/span><\/span>,\u00a0Mouhieddine<\/span>\u00a0TH<\/span><\/span>,\u00a0et al<\/span>.\u00a0Interventions and outcomes of patients with multiple myeloma receiving salvage therapy after BCMA-directed CAR T therapy<\/span>.\u00a0Blood<\/em><\/span>.\u00a02023<\/span>;141<\/span>:756<\/span>\u201365<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/blood.2022017848\/1928339\/blood.2022017848.pdf<\/span><\/p>\r\n

<\/span>88.<\/span>\u00a0Cohen<\/span>\u00a0AD<\/span><\/span>,\u00a0Garfall<\/span>\u00a0AL<\/span><\/span>,\u00a0Dogan<\/span>\u00a0A<\/span><\/span>,\u00a0et al<\/span>.\u00a0Serial treatment of relapsed\/refractory multiple myeloma with different BCMA-targeting therapies<\/span>.\u00a0Blood Adv<\/em><\/span>.\u00a02019<\/span>;3<\/span>:2487<\/span>\u201390<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/bloodadvances.2019000466<\/span><\/p>\r\n

89.<\/span>\u00a0Gazeau<\/span>\u00a0N<\/span><\/span>,\u00a0Beauvais<\/span>\u00a0D<\/span><\/span>,\u00a0Yakoub-Agha<\/span>\u00a0I<\/span><\/span>,\u00a0et al<\/span>.\u00a0Effective anti-BCMA retreatment in multiple myeloma<\/span>.\u00a0Blood Adv<\/em><\/span>.\u00a02021<\/span>;5<\/span>:3016<\/span>\u201320<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/bloodadvances.2021004176<\/span><\/p>\r\n

90.<\/span>\u00a0Da Vi\u00e0<\/span>\u00a0MC<\/span><\/span>,\u00a0Dietrich<\/span>\u00a0O<\/span><\/span>,\u00a0Truger<\/span>\u00a0M<\/span><\/span>,\u00a0et al<\/span>.\u00a0Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma<\/span>.\u00a0Nat Med<\/em><\/span>.\u00a02021<\/span>;27<\/span>:616<\/span>\u20139<\/span>.\u00a0DOI<\/span>:\u00a010.1038\/s41591-021-01245-5<\/span><\/p>\r\n

<\/span><\/span><\/span><\/span><\/span><\/span><\/span><\/span>91.<\/span>\u00a0Martin<\/span>\u00a0N<\/span><\/span>,\u00a0Thompson<\/span>\u00a0E<\/span><\/span>,\u00a0Dell\u2019Aringa<\/span>\u00a0J<\/span><\/span>,\u00a0et al<\/span>.\u00a0Correlation of tumor BCMA expression with response and acquired resistance to idecabtagene vicleucel in the karMMa study in relapsed and refractory multiple myeloma<\/span>.\u00a0Presented at: EHA 2020, virtual, 11-21 June 2020. EP985<\/span>.<\/p>\r\n

92.<\/span>\u00a0Mailankody<\/span>\u00a0S<\/span><\/span>,\u00a0Delvin<\/span>\u00a0SM<\/span><\/span>,\u00a0Landa<\/span>\u00a0J<\/span><\/span>.\u00a0GPRC5D-targeted CAR T cells for myeloma<\/span>.\u00a0N Engl J Med<\/em><\/span>.\u00a02022<\/span>;387<\/span>:1196<\/span>\u2013206<\/span>.\u00a0DOI<\/span>:\u00a010.1056\/NEJMc2213985<\/span><\/p>\r\n

93.<\/span>\u00a0Mouhieddine<\/span>\u00a0TH<\/span><\/span>,\u00a0Van Oekelen<\/span>\u00a0O<\/span><\/span>,\u00a0Melnekoff<\/span>\u00a0DT<\/span><\/span>,\u00a0et al<\/span>.\u00a0Sequencing T-cell redirection therapies leads to deep and durable responses in relapsed\/refractory myeloma patients<\/span>.\u00a0Blood Adv<\/em><\/span>.\u00a02022<\/span>;7<\/span>:1056<\/span>\u201364<\/span>.\u00a0DOI<\/span>:\u00a010.1182\/bloodadvances.2022007923<\/span><\/p>","wpcf-article_received_date":"20230327","wpcf-article_accepted_date":"20230411","wpcf-article_published_online":"20230427","wpcf-podcast":"","wpcf-ogg":"","wpcf-article_end_page":"","wpcf-article_start_page":"","wpcf-acknowledgements":"","wpcf-errata_pdf":"","wpcf-article_flipper_image":"","wpcf-corrected_online":null,"wpcf-supplementary_information":"","wpcf-article_highlight_pdf":"","data_availability":"Data sharing is not applicable to this article as no datasets were generated or analysed during the writing of this study.","digital_features":""},"_links":{"self":[{"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/posts\/71222"}],"collection":[{"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/users\/100366"}],"replies":[{"embeddable":true,"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/comments?post=71222"}],"version-history":[{"count":14,"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/posts\/71222\/revisions"}],"predecessor-version":[{"id":81947,"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/posts\/71222\/revisions\/81947"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/media\/46865"}],"wp:attachment":[{"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/media?parent=71222"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/categories?post=71222"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/tags?post=71222"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}