Carolina D. Schinke, MD, associate professor, medicine, Myeloma Center, University of Arkansas for Medical Sciences, discusses the safety profile of talquetamab-tgvs (Talvey) in the phase 1/2 MonumenTAL-1 trial (NCT04634552) of patients with relapsed/refractory multiple myeloma.

The MonumenTAL-1 trial evaluated the safety and efficacy of the first-in-class, GPRC5D-targeted bispecific antibody talquetamab in patients with treatment-naïve or relapsed/refractory multiple myeloma. In patients that have been previously exposed to T-cell redirection therapy (TCR).

Updates findings from the phase 2 portion of the trial were presented at the 2023 ASCO Annual Meeting, revealing that high, durable responses were produced with talquetamab across all cohorts and that the agent was well tolerated. Based on these data, t

alquetamab was granted accelerated approval by the FDA on August 10, 2023

, for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 4 prior therapies, not including a prior bispecific antibody.

This safety analysis revealed that cytokine release syndrome (CRS) was reported in 79.0% of patients without prior exposure to T-cell redirecting therapy who were treated with talquetamab, Schinke begins. However, most events were low-grade, occurring early in the disease course during step-up dosing or with the first full dose, and were successfully treated with supportive measures, she states. However, some patients did require tocilizumab (Actemra) to manage their CRS, Schinke notes. The incidence of immune effector cell–associated neurotoxicity syndrome (ICANS) was also low, occurring in up to 11.0% of patients across cohorts, Schinke reports.

Several adverse effects (AEs) unique to talquetamab were also observed, Schinke continues. These included skin changes, nail changes and dysgeusia. Over half of patients reported skin changes, such as a rash or dry skin, but these instances were primarily cosmetic and grade 1/2, Schinke details. Although cases of dysgeusia were reported as grade 1/2, no grade 3 and 4 classifications exist, Schinke says. Therefore, a more accurate assessment of the severity of dysgeusia in some patients could not be ascertained, she explains.

Despite their frequency, these AEs did not negatively affect overall quality of life or lead to treatment discontinuation in most patients, Schinke concludes.

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Carolina D. Schinke, MD, discusses the safety profile of talquetamab-tgvs in the phase 1/2 MonumenTAL-1 trial of patients with relapsed/refractory multiple myeloma.

Dr Schinke on the Safety Profile of Talquetamab in Relapsed/Refractory Myeloma

Carolina D. Schinke, MD, associate professor, medicine, Myeloma Center, University of Arkansas for Medical Sciences, discusses the rationale for conducting the phase 1/2 MonumenTAL-1 trial (NCT04634552) in patients with multiple myeloma.

Patients who have received several previous treatments for relapsed/refractory multiple myeloma have an unmet need that should be addressed, Schinke begins, stating that few treatment options exist for this population. In response to this unmet need, investigators launched the phase 1/2 MonumenTAL-1 trial of talquetamab-tgvs (Talvey), a GPRC5DxCD3 bispecific antibody, in patients with relapsed/refractory disease. At the 2023 ASCO Annual Meeting, investigators shared data from the trial. Talquetamab is a novel immunotherapy that is part of a new class of bispecific antibodies, Schinke says. Notably, novel immunotherapies are gaining traction in multiple myeloma, especially in relapsed/refractory disease, she explains.

Moreover, prior early-phase clinical trials showed impressive response rates of approximately 70% with talquetamab in patients with relapsed/refractory multiple myeloma, a previously unseen response rate in this patient population, which is typically refractory to most treatments, Schinke expands. With these encouraging results from early clinical trials, investigators moved this research to a phase 1/2 clinical trial that evaluated talquetamab in this patient population, Schinke said.

Some patient cohorts treated with talquetamab in the MonumenTAL-1 trial had received prior T-cell redirecting treatment or were pretreated with CAR T-cell therapy, Schinke continues. Conversely, 2 other cohorts did not receive this type of pretreatment and received talquetamab on a different dosing schedule, she adds. One cohort received talquetamab weekly, and the other cohort received talquetamab every other week, Schinke explains. Comparing the dosing schedules of these cohorts was informative because no other clinical trial evaluating a bispecific antibody in patients with multiple myeloma has incorporated different dosing schedules, Schinke says.

Based on the results of MonumenTAL-1, on August 10, 2023, the FDA 

granted accelerated approval to talquetamab

 for patients with relapsed/refractory multiple myeloma.

Carolina D. Schinke, MD, discusses the rationale for conducting the phase 1/2 MonumenTAL-1 trial in patients with multiple myeloma.


Dr Schinke on the Rationale for the MonumenTAL-1 Trial in Multiple Myeloma

Carolina D. Schinke, MD, associate professor, medicine, Myeloma Center, University of Arkansas for Medical Sciences, discusses updated findings from the phase 1/2 MonumenTAL-1 trial (NCT04634552) in patients with multiple myeloma.

In MonumenTAL-1, patients with multiple myeloma who were treatment-naïve or relapsed/refractory to prior T-cell redirection therapy (TCR) received the GPRC5D-targeted bispecific antibody talquetamab at either 0.4 mg/kg weekly or 0.8 mg/kg every 2 weeks. Previous findings from this trial showed that, at a median follow-up of 11.7 months in the patients with relapsed/refractory disease who received the agent at 0.4 mg/kg and 4.2 months in those who received the agent at 0.8 mg/kg, the overall response rates (ORRs) were 70% and 64%, respectively.

At a data cutoff date of January 17, 2023, the ORRs were 74.1%, 71.7%, and 64.7% in patients who received talquetamab at 0.4 mg/kg, those who received the agent at 0.8 mg/kg, and those who had received prior TCR, respectively. Specifically, the ORR was 75.0% in patients who had received prior CAR T-cell therapy and 44.4% in those who had received prior bispecific antibodies. In the 0.4 mg/kg cohort, the very good partial response (VGPR), complete response (CR), and stringent complete response (sCR) rates were 25.9%, 9.8%, and 23.8%, respectively. In the 0.8 mg/kg cohort, the VGPR, CR, and sCR rates were 22.1%, 9.0%, and 29.7%, respectively. In the cohort of patients who had received prior TCR, the VGPR, CR, and sCR rates were 19.6%, 5.9%, and 29.4%, respectively.

At median follow-ups of 18.8 months, 12.7 months, and 14.8 months in patients who received talquetamab at 0.4 mg/kg, those who received the agent at 0.8 mg/kg, and those who had received prior TCR, the median durations of response (DORs) were 9.5 months (95% CI, 6.7-13.3), not reached (NR; 95% CI, 13.0 months-NR), and 11.9 months (95% CI, 4.8-NR), respectively, and the respective 12-month DOR rates in patients who achieved a CR or better were 78.9%, 90.5%, and 80.5%.

This novel bispecific antibody elicited impressive efficacy outcomes in patients with multiple myeloma, Schinke concludes.

Carolina D. Schinke, MD, discusses updated findings from the phase 1/2 MonumenTAL-1 trial in patients with multiple myeloma.

Carolina D. Schinke, MD

Articles

Dr Schinke on the Safety Profile of Talquetamab in Relapsed/Refractory Myeloma

Dr Schinke on the Rationale for the MonumenTAL-1 Trial in Multiple Myeloma

Dr Schinke on Talquetamab in Multiple Myeloma