Bispecific Antibody Shows Promise in R/R Multiple Myeloma

Teclistamab, a bispecific antibody that binds B-cell maturation antigen (BCMA) and CD3 to redirect T cells to multiple myeloma cells, showed promising efficacy in patients with relapsed or refractory disease, according to results from a phase I study.

Forty patients received the recommended phase II dose of subcutaneous teclistamab, which led to an overall response rate of 65% over a median follow-up of 6.1 months, reported Saad Usmani, MD, of Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, and colleagues.

All 157 patients in the study experienced treatment-emergent adverse events (TEAEs), and 80% of patients who received the recommended phase II dose — weekly 1,500 μg/kg, after 60 μg/kg and 300 μg/kg step-up doses — had a grade 3 or 4 TEAE, they noted in The Lancet.

The recommended dosing schedule, as well as the subcutaneous administration of the drug, is “expected to provide convenience for patients and physicians,” Usmani and colleagues wrote.

MajesTEC-1 was an open-label, single-arm study conducted at 12 centers in the U.S. and Europe and included patients 18 and older who had measurable disease and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients had relapsed or refractory disease, or were intolerant of established therapies.

Primary objectives were to identify the recommended phase II dose and to describe the safety and tolerability of the drug at that dose. Secondary endpoints included overall response rate and duration of response.

The study included 157 patients who had undergone a median of six previous lines of therapy and who received at least one dose of teclistamab; 54% received it intravenously, and 46% received it subcutaneously. Forty patients received the recommended phase II dose.

Of the patients who received the recommended dose, 58% achieved a very good partial response or better and 40% achieved a complete response or better.

Median time to first confirmed very good partial response or better was 1 month, while the median time to first confirmed complete response or better was 3 months.

The median duration of response was not reached, and 22 of 26 responders (85%) were alive and continuing treatment after 7.1 months’ median follow-up.

Common hematologic TEAEs among the overall cohort and the phase II dose cohort included neutropenia (48% and 40%, respectively), anemia (33% and 28%, respectively), and thrombocytopenia (23% and 20%, respectively). The most common nonhematologic TEAE was cytokine release syndrome, which occurred in 57% of the overall cohort and 70% of the phase II dose cohort. No TEAEs led to treatment discontinuation in the phase II dose cohort.

Usmani and colleagues acknowledged that the study was limited by the small number of patients in individual dosing cohorts (with the exception of the recommended phase II dose cohort), and the fact that, as a single-arm trial, it was unable to provide a direct comparison with approved or investigational agents for relapsed or refractory multiple myeloma.

However, in a commentary accompanying the study, Dickran Kazandjian, MD, and Ola Landgren, MD, PhD, both of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida, noted that the preliminary results of this trial compared favorably with previously approved multiple myeloma drugs in a highly pretreated patient population.

They also agreed with the study authors that the shorter administration time with the once-weekly subcutaneous dose will have some appeal to patients.

“Teclistamab represents a new era of novel immunotherapies, harnesses adaptive anti-tumor responses in vivo, and shows the exponential benefit associated with immunotherapies in multiple myeloma compared with traditional cytotoxic chemotherapies,” they wrote. Questions to be answered, they added, include how the overall benefit of bispecific antibodies compares with CAR T-cell therapy, as well as how new therapies should be sequenced.

“These findings need to be confirmed in a larger patient population; nevertheless, they indicate that teclistamab has encouraging efficacy in patients with relapsed or refractory multiple myeloma who have exhausted standard treatments and the potential to provide substantial improvement over available therapies,” Usmani and colleagues concluded.