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Teclistamab Plus Daratumumab Shows Improved Clinical Efficacy in Pretreated Multiple Myeloma

MM

In patients with relapsed/refractory multiple myeloma (MM) who have previously received an anti-CD38 therapy, the combination of teclistamab and daratumumab may improve clinical efficacy, according to longer follow-up data from the phase Ib TRIMM-2 study.“Upregulation of CD38+/CD8+ T cells and proinflammatory cytokines was observed after teclistamab dosing in combination with daratumumab, supporting potential synergy of the combination in patients with prior anti-CD38 exposure,” the researchers noted.

Teclistamab is a bispecific antibody that binds B-cell maturation antigen (BCMA) and CD3 to redirect T cells to MM cells. Daratumumab is a CD38-targeting monoclonal antibody with direct on-tumor and immunomodulatory mechanisms of action.

Preliminary results from the TRIMM-2 study showed tolerable safety with no overlapping toxicities and encouraging efficacy against relapsed/refractory MM with this combination.

For this portion of the study, the primary objectives were to identify the recommended phase II dose of the combination and to assess safety. The study enrolled adult patients with MM and who had been previously treated with three or more prior lines of therapy, including a proteosome inhibitor and immunomodulatory drug or those who were double-refractory to both. Patients who had received anti-CD38 treatment within 90 days of the study’s start were excluded. About half of patients (52%) were female, and the median age was 67 years (range, 50-79 years).

All patients received subcutaneous (SC) daratumumab 1,800 mg per approved schedule. Administration of teclistamab varied by treatment group:

  • Group one: teclistamab 1.5 mg/kg SC once weekly
  • Group two: teclistamab 3 mg/kg SC once weekly
  • Group three: teclistamab 3 mg/kg SC twice weekly

Among 37 response-evaluable patients, the overall response rate was 78% (n=29/37), and 27 patients (73%) had a very good partial response (VGPR) or better. Based on teclistamab dosing, 14 patients received a VGPR or better in group one, four in group two, and nine in group three.

The most common adverse event was cytokine release syndrome (61%), all cases of which were grade 1 or 2 per American Society for Transplantation and Cellular Therapy guidelines; median time to onset was two days, and median duration was two days. Other adverse events included neutropenia (54%), anemia (46%), thrombocytopenia (33%), and diarrhea (33%).

“Responders to the combination of teclistamab plus SC daratumumab included patients with prior exposure to BCMA or anti-CD38 targeted agents, which is encouraging,” said principal investigator Paula Rodríguez-Otero, MD, PhD, of the Department of Hematology, Clínica Universidad de Navarra, in Pamplona, Spain. “These data also suggest this steroid-sparing regimen may lead to a clinically efficacious regimen in highly refractory patients.”

Reference

Rodriguez Otero, D’Souza A, Reece D, et al. Teclistamab in combination with daratumumab, a novel, immunotherapy-based approach for the treatment of relapsed/refractory multiple myeloma: updated phase 1b results. Abstract #S132. Presented at the 2022 European Hematology Association Congress, June 9-12, 2022.

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