Talquetamab plus daratumumab demonstrated durable and deep responses in heavily pre-treated patients with refractory multiple myeloma (MM). Furthermore, the combination regimen was tolerable and did not show overlapping toxicity. This novel dual therapy is therefore a promising option for the treatment of patients with MM [1]. Daratumumab is a human monoclonal antibody targeting CD38 and talquetamab is a first-in-class T cell-redirecting antibody, targeting GPRC5D and CD3 receptors, explained Dr Ajai Chari (Mount Sinai School of Medicine, NY, USA), main author of the current study. The multicentre, open-label, phase 1b TRIMM-2 trial (NCT04108195) investigated the safety and efficacy of a combination regimen of daratumumab (subcutaneous, as per label) plus talquetamab (subcutaneous, in 3 possible regimen: 400 μg/kg, every 2 weeks; 400 μg/kg, every week; or 800 μg/kg, every 2 weeks). In total, 29 heavily pre-treated patients were included in the study. A high proportion of patients had followed prior anti-BCMA therapy (55.2%) or were classified as anti-CD38 refractory (65.5%) or triple-class refractory (51.7%). After a median follow-up period of 4.2 months, the overall response rate for the combination regimen of talquetamab plus daratumumab was between 77.8% and 85.7%, depending on the administered talquetamab dose. Moreover, the response to therapy was durable and deep in a significant proportion of the patients: between 11.1% and 28.6% of the patients displayed a complete response and 40.0% to 55.6% of the population demonstrated a very good partial response. The combination regimen was tolerable and no new safety issues were reported. In addition, no overlapping toxicities were observed. Any grade neutropenia or thrombocytopenia occurred in 41.4% and 34.5% of the patients, respectively. These events resolved in the majority of patients. One patient discontinued due to an haematologic adverse event (AE). Cytokine release syndrome (55.2%, all grade 1 or 2), dysgeusia, and skin-related disorders were the most common non-haematologic AEs. Infections were reported in 10 patients, 3 of which were classified as grade 3 or higher. The results of this phase 1b trial indicate that the novel immunotherapy-based approach of talquetamab plus daratumumab is promising for the treatment of MM.

  1. Chari A, et al. Phase 1b Results for Subcutaneous Talquetamab Plus Daratumumab in Patients with Relapsed/Refractory Multiple Myeloma. O653, ASH 2021 Scientific Sessions, 11–14 December.

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