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.

Graphical abstract

Figure 1.

Timing and severity of clinically relevant infections by location and etiology. (A) 0.4 mg/kg weekly cohort. (B) 0.8 mg/kg EOW cohort. (C) Prior TCR cohort. The y-axis (days) was the relative start date of the AE. Patients with multiple infections are represented as separate points on the plot. Patients included once on the plot are represented as circles, whereas patients included more than once are represented as triangles. Two patients were excluded from the location figures: 1 had a central nervous system event in the EOW cohort, and 1 had a dental event in the prior TCR cohort.

Figure 2.

Risk of infections over time across cohorts. (A) Any-grade infections. (B) Grade ≥3 infections.

Figure 3.

Cytopenias over time in the weeekly and EOW cohorts. (A) Neutrophil levels. (B) Platelet levels. (C) Hemoglobin levels. Data presented are based on laboratory values. SE, standard error.

Figure 4.

CD19⁺ B-cell levels from baseline through cycle 7 in all cohorts. Points represent the median B-cell count and whiskers show the median absolute deviation. At baseline, n = 52 in the qw cohort, n = 52 in the q2w cohort, and n = 18 in the prior TCR cohort.

Figure 5.

Mean polyclonal IgG adjusted cells during treatment. IgG was assessed monthly. The majority of samples collected were based on central laboratory testing. Polyclonal IgG was estimated for patients with IgG MM by subtracting M-spike protein values from total IgG values. These calculated values, along with measured IgG levels for patients with non-IgG MM, were assessed to derive mean IgG levels during treatment. Patients who received IV immunoglobulin before receiving talquetamab were included.