Paula Rodriguez-Otero, MD, from the University of Navarra, discusses the TRiMM-2 study of teclistamab and talquetamab in combination with daratumumab in the treatment of relapsed/refractory multiple myeloma. Results from this study were recently presented in two abstracts at The American Society of Hematology Meeting & Exposition (ASH 2021).
Multiple myeloma is a rare blood cancer associated with uncontrolled growth of plasma cells. While the disease is treatable, relapses are common and some patients are refractory to first line treatment.
The TRiMM-2 study (NCT04108195) is an ongoing phase 1b study to determine phase 2 doses for each treatment combination (between daratumumab plus talquetamab, and teclistamab plus daratumumab with or without pomalidomide) and to characterize the safety profiles of the combinations. In two ASH 2021 abstracts (Abstract 1647 and Abstract 161), results from the TRiMM-2 study were reported; Dr. Rodriguez Otero presented data from the former abstract which reports initial findings of teclistamab plus daratumumab in relapsed/refractory multiple myeloma patients.
As Dr. Rodriguez-Otero explains, eligible patients were ≥18 years of age with an multiple myeloma diagnosis and had received ≥3 prior lines of therapy or were double refractory to a proteasome inhibitor and immunomodulatory drug. The primary objectives were to identify the phase 2 recommended dose for the teclistamab + daratumumab combination and evaluate its safety.
Currently, 33 patients in the TRiMM-2 study have received subcutaneous teclistamab + daratumumab. They have been divided into the following dosing cohorts:
- daratumumab 1800 mg + teclistamab 1500 µg/kg weekly (n=21),
- daratumumab 1800 mg + teclistamab 3000 µg/kg weekly (n=5),
- daratumumab 1800 mg + teclistamab 300 mg biweekly starting Cycle 3 Day 1 (teclistamab 150 mg weekly in Cycles 1–2; n=2),
- daratumumab 1800 mg + teclistamab 3000 µg/kg biweekly (n=5).
As of the data cutoff (Jun 22, 2021), median follow-up across teclistamab + daratumumab cohorts was 3.6 months.
Overall, 97.0% of patients had ≥1 adverse event (AE) of any grade; of which 66.7% had grade 3/4 AEs. The most common AE was cytokine release syndrome (54.5%; all grade 1/2). The most common grade 3/4 AEs were neutropenia (36.4%), thrombocytopenia (33.3%), anemia (24.2%), and diarrhea (3.0%). No immune effector cell-associated neurotoxicity syndrome (ICANS) events were reported. One patient in the daratumumab 1800 mg + teclistamab 3000 µg/kg weekly cohort died due to bacterial pneumonia (unrelated to treatment) during Cycle 1, and 1 in the daratumumab 1800 mg + teclistamab 1500 µg/kg weekly cohort died due to progressive disease. Across teclistamab + daratumumab cohorts, median time to first response was 1.0 month. Median duration of response was not reached. Teclistamab + daratumumab treatment led to proinflammatory cytokine production (induction of interferon-γ and tumor necrosis factor-α) and T-cell activation (upregulation of programmed cell death protein-1 and CD38 on peripheral T cells).
To learn more about multiple myeloma and other rare cancers, visit checkrare.com/diseases/cancers/
