Saad Zafar Usmani received his medical education at Allama Iqbal Medical College in Lahore, Pakistan. He completed a residency in internal medicine at Sinai-Grace Hospital/Wayne State University in Detroit, Michigan and a fellowship in hematology and oncology at the University of Connecticut Health Center in Farmington, Connecticut. Dr. Usmani joined the faculty of the Levine Cancer Institute in July 2013; he also currently holds an academic appointment as Clinical Professor of Medicine at the University of North Carolina-Chapel Hill School of Medicine. Previously, Dr. Usmani served as an Assistant Professor of Medicine at the University of Arkansas for Medical Sciences in Little Rock, Arkansas and Director of Developmental Therapeutics at the Myeloma Institute for Research & Therapy. Dr. Usmani is board certified in internal medicine, medical oncology, and hematology, and he is a Fellow of the American College of Physicians. He holds membership in several professional societies, including the International Myeloma Working Group, the SWOG Myeloma Committee, the American Society of Hematology (ASH), the American Society of Clinical Oncology (ASCO), and the American Society of Bone Marrow Transplantation. Dr. Usmani has served as the Track Leader on the ASCO Scientific Committee on Lymphoma and Plasma Cell Disorders, and he is a member of the ASH Committee on Plasma Cell Neoplasia and the National Cancer Institute Myeloma Steering Committee. Dr. Usmani is on the editorial review board of numerous medical journals, has authored/co-authored more than 130 peer-reviewed research manuscripts and 190 abstracts at national and international meetings. Active in clinical and translational research, Dr. Usmani has research interests focus on plasma cell disorders—in particular, high-risk multiple myeloma.
Q. Could you tell us a little about teclistamab and its mechanism of action?
Teclistamab is a bispecific monoclonal antibody where one part of the antibody binds to B-cell maturation antigen on the surface of myeloma cells, while the other binds to CD3 on the surface of the patient’s own T cells. This enables the patient’s T cells to identify and attempt to eliminate the myeloma cells.
Q. What were the aims and design of the phase I study (NCT03145181)?
The study was a dose escalation phase I study to first determine the safety of this antibody in patients and then determine the dose that would be recommended for a phase 2 study.
Q. What were the efficacy and safety findings of this study?
The study, at the time of report in dosing up to 720 ug/kg, showed a safe profile with hematologic side effects being the most common ones, bearing in mind the advanced relapsed/refractory patient population that enrolled on the trial. The cytokine release syndrome (CRS) was observed in 56% of patients, all being grade 1/2. Very low rates of neurological acute encephalitis syndrome were observed.
Q. What was the incidence of CRS and how might this be mitigated?
We employed a step up dosing schema after the first cohort of patients, which likely helped in mitigating the overall percentage and grading of CRS.
Q. How can we select patients most likely to respond to this approach?
We intend to explore that question in the dose expansion cohort of the trial.
Disclosure: Saad Usmani has been a consultant and advisor for Abbvie, Amgen, Celgene, GlaxoSmithKline, Janssen Oncology, Karyopharm Therapeutics, Seattle Genetics, SkylineDX and Takeda. He has been a speaker for Amgen, Celgene, Janssen Oncology and Takeda. He has received research funding for Amgen, Array BioPharma, Bristol-Myers Squibb, Celgene, Janssen Oncology, Pharmacyclics, Sanofi and Seattle Genetics.
Support: Commissioned, edited and supported by Touch Medical Media, who commissioned the interview in liaison with Edelman.
Published: 8 July 2020