Dr Dima on the Mechanism of Action of Teclistamab in Relapsed/Refractory Multiple Myeloma

Danai Dima, MD, hematology-oncology fellow, Cleveland Clinic, discusses the mechanism of action of teclistamab-cqyv (Tecvayli) in pretreated patients with relapsed/refractory multiple myeloma, as well as the rationale for investigating the efficacy and safety of this agent a real-world patient cohort.

Teclistamab is a bispecific antibody that targets BCMA, which is expressed on the surface of plasma cells, and CD3, which is expressed on the surface of T cells, Dima begins. By binding to both BCMA and CD3, teclistamab forms an immunologic bridge that activates T cells, leading to the destruction of malignant plasma cells, she explains.

In October 2022, teclistamab was approved by the FDA for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 4 previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, Dima adds.

This regulatory decision was based on the results of the pivotal phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098), she continues. In the single-arm, open-label, multicenter trial, teclistamab demonstrated an overall response rate of 63.0% (95% CI, 55.2%-70.4%), including a very good partial response or better in 58.8% of patients, and a complete response or better in 39.4% of patients. The agent also produced a median progression-free survival of 11.3 months (95% CI, 8.8-17.1).

Although the MajesTEC-1 trial supported the approval of teclistamab, its stringent eligibility criteria excluded many patients with high-risk features, Dima notes. This included patients with significant organ dysfunction, significant comorbidities, severe cytopenias, high-risk disease characteristics, and prior BCMA-directed therapy exposure, she says. Accordingly, the trial may not have fully represented patients being treated with the agent in clinical practice, according to Dima. To account for this potential discrepancy, a real-world, retrospective study of outcomes with teclistamab in pretreated patients with relapsed/refractory multiple myeloma was conducted, Dima explains.

Findings from the real-world study, presented at the 2023 ASH Annual Meeting, showed that the administration of the T-cell redirecting bispecific antibody was effective and well tolerated in a heavily pretreated patient population, most of whom did not meet the eligibility criteria for the MajesTEC-1 trial and had high-risk disease features. Moreover, the real-world rates of BCMA-related adverse effects are comparable with those in the MajesTEC-1 trial, although the occurrence of severe cytokine release syndrome and neurotoxicity in this patient population was relatively low in comparison, Dima concludes.