New Protocol: Talquetamab with Daratumumab for Rel/Ref Multiple Myeloma

In this phase 3 study, talquetamab plus daratumumab and pomalidomide (Tal-DP) and talquetamab plus daratumumab (Tal-D) significantly improved progression-free and overall survival compared to daratumumab plus pomalidomide and dexamethasone (DPd) in patients with relapsed or refractory multiple myeloma. Both Tal-DP and Tal-D also showed higher overall response rates and complete response rates than DPd. GPRC5D-related adverse events were common but generally manageable and did not frequently lead to treatment discontinuation.

Study

Randomized, open-label, multicenter, phase 3 study [MonumenTAL-3, NCT05455320]

Relapsed or refractory multiple myeloma who had previously received at least one line of therapy

Talquetamab+Daratumumab+Pomalidomide (n=287) vs Talquetamab+Daratumumab (n=287) vs Daratumumab+Pomalidomide+Dexamethasone (n=290)

Efficacy

ORR: 88.2% vs. 88.5% vs. 77.6% (Tal-DP vs. Tal-D vs. DPd)

CR or better: 71.1% vs. 69.0% vs. 34.5%

mRD-negative CR: 52.3% vs. 46.3% vs. 15.9%

24-mo PFS: 81.3% vs. 77.6% vs. 51.2% (HR 0.28 [0.20-0.40] for Tal-DP vs DPd; HR 0.33 [0.24-0.46] for Tal-D vs DPd)

24-mo OS: 89.2% vs. 87.9% vs. 79.1% [73.7-83.6] (HR 0.47 [0.30-0.73] for Tal-DP vs DPd; HR 0.51 [0.33-0.78] for Tal-D vs DPd)

Safety

Grade >=3 AE: Neutropenia (76.4% vs 29.2% vs 86.2%), anemia (23.9% vs 15.0% vs 15.9%), thrombocytopenia (23.9% vs 13.1% vs 13.8%), infection (37.7% vs 29.2% vs 42.4%), diarrhea (2.5% vs 0.7% vs 4.6%)

Serious adverse events: 63.0% vs 52.6% vs 53.7%

Adverse events leading to discontinuation of all agents: 10.5% vs 8.0% vs 6.7%