Talquetamab-Daratumumab in Relapsed or Refractory Myeloma

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Talquetamab is a bispecific antibody targeting GPRC5D and CD3, showing promise in relapsed/refractory multiple myeloma.
• Previous trials indicated durable responses with talquetamab and a manageable safety profile, sparing normal B cells.

Purpose of the Study:

• To evaluate the efficacy and safety of talquetamab combined with daratumumab and pomalidomide (Tal-DP) or talquetamab with daratumumab (Tal-D) versus daratumumab, pomalidomide, and dexamethasone (DPd) in relapsed/refractory multiple myeloma.
• To compare progression-free survival (PFS) as the primary endpoint.

Main Methods:

• A Phase 3 randomized trial enrolled patients with relapsed or refractory multiple myeloma after at least one prior therapy.
• Patients were assigned to receive Tal-DP, Tal-D, or DPd.
• Key endpoints included PFS, overall response rate (ORR), complete response (CR) or better, measurable residual disease (MRD)-negative CR, and overall survival (OS).

Main Results:

• Tal-DP and Tal-D demonstrated significantly longer PFS compared to DPd (24-month estimates: 81.3% and 77.6% vs. 51.2%, respectively; P<0.001).
• Higher ORR, CR or better, and MRD-negative CR rates were observed in the talquetamab-containing arms.
• OS at 24 months was also improved with Tal-DP (89.2%) and Tal-D (87.9%) versus DPd (79.1%).

Conclusions:

• Both Tal-DP and Tal-D significantly improve PFS in patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy.
• Talquetamab-based combinations represent a significant advancement in treating relapsed/refractory multiple myeloma.
• The study was funded by Johnson & Johnson (NCT05455320).