Dr Kin on Clinical Implications of the FDA Approval of Teclistamab in R/R Multiple Myeloma

Andrew Kin, MD, medical oncologist, Barbara Ann Karmanos Cancer Institute, discusses clinical implications of the FDA approval for teclistamab-cqyv (Tecvayli) in relapsed/refractory multiple myeloma.

In October 2022, teclistamab became the first BCMA-/CD3-targeted bispecific antibody to receive FDA approval for the treatment patients with relapsed/refractory multiple myeloma who received at least 4 previous lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody. This regulatory decision was based on data from the single-arm, multicenter, phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098), in which teclistimab produced an objective response rate of 61.8% (95% CI, 52.1%-70.9%). Of these responses, 28.2% of patients achieved a complete response (CR) or better, 29.1% achieved a very good partial response, and 4.5% achieved a partial response. At a median follow-up of 7.4 months, the 6-month duration of response (DOR) rate at 6 months with teclistamab was 90.6%, and the 9-month DOR rate was 66.5%.

The approval of teclistamab signifies a potential role for this class of BCMA-targeted agents and other bispecific T-cell engagers for patients with heavily pretreated multiple myeloma, Kin states. Agents like teclistamab contain dual binding sites for BCMA and CD3, Kin continues. Similar to monoclonal antibodies, teclistamab targets BCMA expressed on the surface of myeloma cells at one bindings site, and targets CD3 expressed on the surface of T cells at the other. In doing so, the agent redirects CD3+ T cells to BCMA+ myeloma cells, which promotes T-cell activation and tumor cell lysis, Kin explains.

Notably, the primary toxicity observed with these T-cell–based products is cytokine release syndrome (CRS), Kin adds. Early identification and management of CRS events is vital for improving patient outcomes, he says. However, the advantage of teclistamab and other T-cell engaging products is their ability to produce significant and deep responses, Kin emphasizes. Moreover, they can also result in minimal residual disease (MRD) negativity. MRD-negative responses are not only uncommon at this disease stage but are also infrequent in heavily pretreated patients, he states. Accordingly, the bispecific T-cell–engager platform has been shown to be a highly active and viable option for these patients, who historically lack effective therapeutics, Kin concludes.