Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma | NEJM - nejm.org

Abstract

Background

G protein–coupled receptor, household C, radical 5, subordinate D (GPRC5D) is an orphan receptor expressed successful malignant plasma cells. Talquetamab, a bispecific antibody against CD3 and GPRC5D, redirects T cells to mediate sidesplitting of GPRC5D-expressing myeloma cells.

Methods

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In a signifier 1 study, we evaluated talquetamab administered intravenously play oregon each different week (in doses from 0.5 to 180 μg per kilogram of assemblage weight) oregon subcutaneously weekly, each different week, oregon monthly (5 to 1600 μg per kilogram) successful patients who had heavy pretreated relapsed oregon refractory aggregate myeloma that had progressed with established therapies (a median of six erstwhile lines of therapy) oregon who could not person these therapies without unacceptable broadside effects. The superior extremity points — the frequence and benignant of dose-limiting toxic effects (study portion 1 only), adverse events, and laboratory abnormalities — were assessed successful bid to prime the recommended doses for a signifier 2 study.

Results

At the data-cutoff date, 232 patients had received talquetamab (102 intravenously and 130 subcutaneously). At the 2 subcutaneous doses recommended for a signifier 2 survey (405 μg per kilogram play [30 patients] and 800 μg per kilogram each different week [44 patients]), communal adverse events were cytokine merchandise syndrome (in 77% and 80% of the patients, respectively), skin-related events (in 67% and 70%), and dysgeusia (in 63% and 57%); each but 1 cytokine merchandise syndrome lawsuit were of people 1 oregon 2. One dose-limiting toxic effect of people 3 rash was reported successful a diligent who had received talquetamab astatine the 800-μg dose level. At median follow-ups of 11.7 months (in patients who had received talquetamab astatine the 405-μg dose level) and 4.2 months (in those who had received it astatine the 800-μg dose level), the percentages of patients with a effect were 70% (95% assurance interval [CI], 51 to 85) and 64% (95% CI, 48 to 78), respectively. The median duration of effect was 10.2 months and 7.8 months, respectively.

Conclusions

Cytokine merchandise syndrome, skin-related events, and dysgeusia were communal with talquetamab attraction but were chiefly low-grade. Talquetamab induced a important effect among patients with heavy pretreated relapsed oregon refractory aggregate myeloma. (Funded by Janssen Research and Development; MonumenTAL-1 ClinicalTrials.gov number, NCT03399799.)