Clinical features and management of GPRC5D-associated adverse events in novel GPRC5D × CD3 bispecific talquetamab-treated relapsed/refractory multiple myeloma patients: the MonumenTAL-1 China cohort experience.

OBJECTIVES

Talquetamab (G-protein-coupled receptor class C group 5 member D [GPRC5D] × CD3 bispecific antibody) demonstrated antitumor activity in relapsed/recurrent multiple myeloma (RRMM) in the phase I/II MonumenTAL-1 study. We report the safety profile of talquetamab in Chinese patients from MonumenTAL-1, focusing on GPRC5D-associated on-target/off-tumor adverse events (AEs).

METHODS

Adult Chinese patients with heavily pretreated RRMM and measurable disease received subcutaneous talquetamab 0.4 mg/kg once weekly (QW) or 0.8 mg/kg biweekly (Q2W). Incidence, time to onset, duration, and recovery status of GPRC5D-associated AEs were reported. Data cutoffs: 29 February 2024 (QW cohort); 26 August 2024 (Q2W cohort).

RESULTS

A total of 41 adult Chinese patients were included in this study (QW cohort, n = 29; Q2W cohort n = 12). Median treatment duration was 7.7 months (QW cohort) and 7.1 months (Q2W cohort); median follow-up was 16.3 and 13.9 months, respectively. GPRC5D on-target/off-tumor AEs, predominantly grade 1-2 (one grade 3 non-rash skin toxicity; QW cohort), were most commonly oral AEs (dysgeusia, dry mouth), skin AEs (rash, non-rash skin toxicity), and nail disorders; 50%-100% resolved by data cutoff. AEs were managed with supportive therapies. Talquetamab dose modification was needed in one case (grade 2 weight decrease).

DISCUSSION: The generally mild GPRC5D-associated AEs were well tolerated and consistent with the known safety profile of talquetamab. Supportive management of these AEs without need for dose modification enabled prolonged treatment.

CONCLUSIONS

Education of patients with RRMM on potential GPRC5D-associated AEs before starting treatment, and timely management upon experience, may ensure optimum exposure and thus maximum benefit with talquetamab.