Infections and parameters of humoral immunity with talquetamab in relapsed/refractory multiple myeloma in MonumenTAL-1
Carolina Schinke, Paula Rodríguez‐Otero, Niels W.C.J. van de Donk, Brea Lipe, Noa Lavi, Leo Rasche, Samir Parekh, Oliver Van Oekelen, Deeksha Vishwamitra, Sheri Skerget, Diana Cortés‐Selva, Raluca Verona, Brandi Hilder, Tara Masterson, Michela Campagna, Sheetal Khedkar, Thomas Renaud, Jaszianne Tolbert, Colleen Kane, Kathleen Gray, Ibrahim Saber, Christoph Heuck, Ajai Chari
Abstract
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.