Treatment selection for patients with RRMM is challenging and the optimal sequence and choice of drugs is not established. Treatment-related factors, such as type and response to prior therapy, are critical for the selection of a new treatment regimen; it also depends on a range of patient- and tumour-related factors.¹ 

Abbreviation

RRMM, relapsed/refractory multiple myeloma.

Reference

van de Donk, NWCJ. Hematology Am Soc Hematol Educ Program. 2020;2020:248–58.

A triplet therapy is preferred over dual therapy, since there is evidence that frail patients may have improved outcomes with triplet vs dual therapies; although they are also at higher risk from toxicities vs fit patients.¹ There is insufficient evidence to support retreatment with an alternative anti-CD38 mAb such as Isa in anti-CD38 mAb refractory patients.² There is evidence of increased risk of renal failure with K.³

Abbreviations

Isa, isatuximab; K, carfilzomib; mAb, monoclonal antibody.

References

1. Mian H, et al. Blood Cancer J. 2023;13:6.
2. van de Donk, NWCJ. Hematology Am Soc Hematol Educ Program. 2020;2020:248–58.
3. Mian HS, et al. Ann Hematol. 2021;100:1261–6.

A systematic review highlighted the strong prognostic value of MRD negativity and confirmed its utility as a surrogate for PFS and OS in MM.¹ Subsequently, an analysis of data from the POLLUX (Dara-Rd) and CASTOR (Dara-Vd) trials showed that sustained MRD negativity for ≥6 and ≥12 months  was associated with prolonged PFS.²

From available data for CAR T-cell therapies, a deep initial response, while necessary, is not sufficient for long-term remission.³ Data  from the phase Ib/II CARTITUDE-1 trial further indicates the benefit of sustained MRD negativity. At 27 months’ follow-up, in patients who achieved sustained MRD negativity for ≥6 and ≥12 months, PFS rates were 73.0% and 78.8%; OS rates were 93.5% and 90.8%. Respective values in the overall population were 54.9% and 70.4%.⁴

Abbreviations

CAR, chimeric antigen receptor; d, dexamethasone; Dara, daratumumab; MM, multiple myeloma; MRD, minimal residual disease; OS, overall survival; PFS, progression-free survival; R, lenalidomide; V, bortezomib.

References

1. Munshi N, et al. Blood Adv. 2020;4:5988–99.
2. Avet-Loiseau H, et al. J Clin Oncol. 2021;39:1139–49.
3. Cappell KM, Kochenderfer JN. Nat Rev Clin Oncol. 2023;20:359–71.
4. Martin T, et al. J Clin Oncol. 2023;41:1265–74.

Early data for CAR T cells manufactured after response to induction therapy suggested they may be more clinically effective than those obtained from heavily treated RRMM patients, leading potentially to more durable responses to therapy.¹

Subsequent data from the KarMMa-3 trial demonstrated how treatment with idecabtagene vicleucel significantly prolonged median PFS vs standard regimens in patients with triple-class–exposed RRMM (13.3 vs 4.4 months, p<0.001).²

Abbreviations

CAR, chimeric antigen receptor; PFS, progression-free survival; RRMM, relapsed/refractory multiple myeloma.

References

1. Garfall AL, et al. Blood Adv. 2019;3:2812–5.
2. Rodriguez‑Otero P, et al. N Engl J Med. 2023;388:1002–14.

Evidence indicates that patients can be successfully treated with a BsAb following CAR T-cell therapy,¹ and that earlier referral for CAR T-cell therapy increases the likelihood of successful infusion.²

The ADC belantamab mafodotin-blmf is not currently approved for use, although NCCN guidelines state that it can be useful in certain circumstances, if available through a compassionate use programme.³

Alkylating drugs like bendamustine reduce the number and function of T cells, potentially reducing the efficacy of subsequent BsAb or CAR T-cell therapy.⁴ 

Abbreviations

BsAb, bispecific antibody; CAR, chimeric antigen receptor; NCCN, National Comprehensive Cancer Network.

References

1. Touzeau C, et al. HemaSphere. 2022;6:85–6.
2. Cohen AD, et al. Blood. 2023;141:219–30.
3. NCCN. Multiple myeloma. Version 3.2023. Available at: www.nccn.org/login?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf (accessed 31 May 2023).
4. van de Donk, NWCJ. Hematology Am Soc Hematol Educ Program. 2020;2020:248–58.