Talquetamab and Daratumumab in Relapsed or Refractory Myeloma

Key Takeaways

• Both talquetamab-containing regimens were associated with longer progression-free survival than the daratumumab-based control at interim analysis.
• Overall response, complete response or better, and MRD-negative complete response were higher with Tal-DP and Tal-D than with DPd.
• Investigators reported 24-month overall survival estimates and rates of serious and fatal adverse events in all three groups.

At a median follow-up of 24.6 months, the randomized phase 3 MonumenTAL-3 trial found lower risks of disease progression or death with talquetamab plus daratumumab, with or without pomalidomide, than with daratumumab plus pomalidomide and dexamethasone in relapsed or refractory multiple myeloma. Hazard ratios were 0.28 for Tal-DP versus DPd and 0.33 for Tal-D versus DPd. Both talquetamab-containing regimens were also associated with longer progression-free survival than the control regimen.

MonumenTAL-3 was a phase 3 randomized trial in patients with relapsed or refractory multiple myeloma after at least one prior line of therapy. Patients were assigned to talquetamab plus daratumumab and pomalidomide, talquetamab plus daratumumab, or daratumumab plus pomalidomide and dexamethasone. The Tal-DP, Tal-D, and DPd groups included 287, 287, and 290 patients.

At 24 months, progression-free survival was estimated at 81.3% with Tal-DP, 77.6% with Tal-D, and 51.2% with DPd, with P<0.001 for both comparisons. Overall response rates were 88.2%, 88.5%, and 77.6% across the three groups. Complete response or better occurred in 71.1%, 69.0%, and 34.5%, and MRD-negative complete response occurred in 52.3%, 46.3%, and 15.9%. The gap from DPd widened in the more stringent response categories, particularly for complete and MRD-negative responses. P values were below 0.001 for all response comparisons, and both talquetamab-containing regimens were associated with deeper responses than DPd.

The 24-month overall survival estimates were 89.2% with Tal-DP, 87.9% with Tal-D, and 79.1% with DPd. Hazard ratios for death were 0.47 for Tal-DP versus DPd and 0.51 for Tal-D versus DPd, with 95% confidence intervals of 0.30 to 0.73 and 0.33 to 0.78. These overall survival data were part of the interim analysis at the same follow-up point. Serious adverse events occurred in 63.0% of Tal-DP patients, 52.6% of Tal-D patients, and 53.7% of DPd patients. Fatal adverse events occurred in 1.8%, 4.0%, and 4.6%, respectively, across the three randomized groups.