On August 9, 2023, the bispecific GPRC5D (G protein–coupled receptor, class C, group 5)-directed CD3 T-cell engager talquetamab-tgvs was granted accelerated approval by the U.S. Food and Drug Administration for treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody).¹

Supporting Efficacy Data

Approval was supported by findings from the MonumenTAL-1 trial (ClinicalTrials.gov identifier NCT03399799, NCT4634552). This study included 187 patients; 100 received talquetamab at 0.4 mg/kg subcutaneously (SC) weekly (following two step-up doses in the first week of therapy) and 87 received talquetamab at 0.8 mg/kg SC every 2 weeks (following three step-up doses) until disease progression or unacceptable toxicity.

Partial response or better on independent review committee assessment was achieved in 73 of 100 patients (73%, 95% confidence interval (CI) = 63.2%–81.4%) receiving 0.4 mg/kg weekly, with a median response duration of 9.5 months (95% CI = 6.5 months to not estimable) and in 65 of 87 patients (73.6%, 95% CI = 63%–82.4%) receiving 0.8 mg/kg every 2 weeks, with a median response duration not reached. Response was maintained for at least 9 months in an estimated 85% of responders.

How It Is Used

The recommended dosage of talquetamab is 0.4 mg/kg weekly or 0.8 mg/kg biweekly with, as specified in product labeling, step-up doses during the first week of treatment. Labeling provides instructions on premedication and dosage modification for adverse reactions (such as cytokine-release syndrome [CRS] and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome [ICANS]).

Safety Profile

Among 339 patients in the MonumenTAL-1 safety population, the most common adverse events of any grade were pyrexia (83%), CRS (76%), dysgeusia (70%), nail disorder (50%), musculoskeletal pain (43%), skin disorder (41%), rash (38%), fatigue (37%), increased weight (35%), and dry mouth (34%). The most common grade 3 or 4 adverse events included bacterial infection such as sepsis (9%), pyrexia (4.7%), and fatigue and rash (3.5% each). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocyte (80%), white blood cell (35%), and neutrophil counts (35%).

Serious adverse events occurred in 47% of patients, most commonly CRS (13%), bacterial infection including sepsis (8%), pyrexia (4.7%), ICANS (3.8%), COVID-19 (2.7%), neutropenia (2.1%), and upper respiratory tract infection (2.1%). Adverse events led to treatment discontinuation in 9%, most commonly (> 1%) ICANS. Adverse events led to death in 3.2% of patients, including COVID-19, dyspnea, and general physical health deterioration in 0.6% each and bacterial infection including sepsis, basilar artery occlusion, fungal infection, infection, and pulmonary embolism in 0.3% each.

Talquetamab-tgvs has a boxed warning for CRS and neurologic toxicity including ICANS. Because of these risks, talquetamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli-Talvey REMS. Talquetamab also has warnings or precautions for oral toxicity and weight loss, infections, cytopenia, skin toxicity, hepatotoxicity, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving talquetamab. 

REFERENCE

1. Talvey (talquetamab-tgvs) injection, for subcutaneous use, prescribing information, Janssen Pharmaceutical Companies, August 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761342s000lbl.pdf. Accessed September 6, 2023.