Paula Rodríguez-Ortero, MD, PhD, Hematologist at the University of Navarra, discusses results of PD-1 inhibitor combination therapy in patients with multiple myeloma (MM).
MM is a bone marrow-based plasma cell neoplasm characterized by a serum monoclonal protein and skeletal destruction. Common symptoms include osteolytic lesions, pathological fractures, bone pain, hypercalcemia, and anemia. The exact underlying cause of multiple myeloma is currently unknown. Most patients with MM require multiple lines of therapy as patients are prone to relapse and/or refractory to therapy.
The TRIMM-3 clinical trial (NCT05338775) is a phase 1b, multicenter, open-label study aimed at identifying safe doses, and evaluating safety and tolerability of the combination talquetamab and cetrelimab in patients with relapsed or refractory MM. Talquetamab is a bispecific antibody designed to target GPRC5D expressed on the surface of MM cells. Cetrelimab is a monoclonal antibody that inhibits programmed cell death receptor-1 (PD-1) to enhance T-cell function and antitumor immunity. The study enrolled 44 patients with relapsed or refractory MM.
Results
The safety findings with the combination therapy are consistent with those seen in trials of each drug. GPRC5D-related adverse events were common and included changes in taste, nail, skin, and rash. PD-1-related adverse events were observed in 7 patients. Grade 3/4 adverse events occurred in 82% of patients with the most common being neutropenia and anemia. Additionally, cytokine release syndrome was observed in 61% of patients and infections in 80% of patients. Five patients experienced adverse events that led to discontinuation of treatment.
Overall response rate was 70%, six-month duration of response was 93%, and progression free survival was 72%. In patients with prior CD3 redirecting antibody therapy, overall response rate was 68%, six-month duration of response was 92%, and progression free survival was 65%. No reduction in B-cell counts was observed and proportion of plasma cells expressing GPRC5D or PD-L1 was maintained. These patients also experienced higher recovery of T cells and costimulatory molecule expression in Cd8 T cells in cycle 3 versus cycle 2.
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