Infections and parameters of humoral immunity with talquetamab in relapsed/refractory multiple myeloma in MonumenTAL-1

ABSTRACT: Talquetamab is the first approved GPRC5D-targeting bispecific antibody for the treatment of relapsed/refractory multiple myeloma (RRMM), based on results from the phase 1/2 MonumenTAL-1 study. We report the infection profile among patients treated with talquetamab in MonumenTAL-1. Patients with triple-class exposed RRMM received subcutaneous talquetamab 0.4 mg/kg weekly or 0.8 mg/kg every other week (EOW). Patients with prior T-cell redirection therapy (TCR) were included in a separate cohort and received either schedule. Infections (graded by Common Terminology Criteria for Adverse Events v4.03) were managed per local guidelines. Patients received talquetamab (N = 339) with a median follow-up of 18.8 (weekly; n = 143), 12.7 (EOW; n = 145), and 14.8 (prior TCR; n = 51) months. Infections occurred in 58.7%, 66.2%, and 72.5% of patients, respectively; most common were respiratory infections, including COVID-19. Grade 3/4 infections occurred in 21.7% (weekly), 15.9% (EOW), and 27.5% (prior TCR) of patients, onset most common in cycles 1/2. Opportunistic infections were low (3.5%, 5.5%, and 5.9%, respectively). Five patients died due to infections. Neutrophil levels recovered at cycle 2 and were maintained throughout treatment. B-cell levels remained stable in early cycles, with notable increases at cycle 7. Immunoglobulin G levels recovered after cycle 3 and increased through cycle 17. Few patients started IV immunoglobulin following talquetamab (9.8% [weekly], 6.9% [EOW], and 5.9% [prior TCR]). Patients treated with talquetamab demonstrated relatively low rates of grade 3/4 infections and preservation of humoral immunity, distinguishing talquetamab as an important and potentially less immunosuppressive, novel treatment option for patients with RRMM. These trials were registered at www.clinicaltrials.gov as #NCT03399799 and #NCT04634552.