Hans C. Lee, MD, discusses the toxicity seen with the BCMA/CD3 bispecific antibody linvoseltamab for patients with relapsed/refractory multiple myeloma.
Hans C. Lee, MD, associate professor and director of multiple myeloma clinical research in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center, discussed the results of the phase 2 LINKER-MM1 study (NCT03761108) evaluating linvoseltamab (REGN5458) for patients with relapsed/refractory multiple myeloma.
These data were presented at the 2023 American Socitey of Clinical Oncology Annual Meeting that looked at 2 different dose levels of the BCMA/CD3 bispecific antibody. A cohort of patients on 50-mg (n = 104) of linvoseltamab were compared with a cohort on 200 mg (n = 117) of the drug, with the higher dose eliciting an objective response rate of 71%. Fourteen-percent of patients with a response to the 200 mg dose had a complete response (CR) and 16% had a stringent CR. Further, 29% had a very good partial response and 12% had a partial response while 6-month estimated progression-free survival was 72.7%, however, median PFS was not reached.
For both cohorts, step-up dosing was used in week 1 and 2 to minimize toxicity. Adverse events (AEs) were observed in this heavily pretreated patient population, with Lee noting that cytokine release syndrome (CRS) was the most common AE observed. Moreover, infections like Pneumocystis jirovecii pneumonia were seen in 3 patients, but overall toxicity was deemed tolerable to move on to a phase 3 study with this drug (NCT05730036).
0:08 | The most common AE seen across the study was cytokine release syndrome, which occurred in 55% of patients in the 50 mg cohort and occurred in 45% of patients in the 200 mg cohort. In the 200 mg court, most [cases] of CRS was grade 1 in severity, [and] 35% of patients had grade 1 CRS, 9% of patients had grade 2 CRS, and there was a single grade 3 CRS event. When it did occur, CRS occurred typically within the same day of dosing and resolved typically within 24 hours of dosing, hence, the limited hospitalization required for the study with 24 hospitalizations required only for the initial 2 step-up doses of the drug.
0:46 | Other AEs of interests are certainly infections with bispecific antibodies as a drug class. So, across the study, there was a similar rate of infection between the 50 mg and 200 mg cohorts. Infections occurred in about 60% of cases in either arm, and about 35% of cases were grade 3 or higher in severity.