Talquetamab–Daratumumab in Relapsed or Refractory Myeloma
Talquetamab plus daratumumab, with or without pomalidomide, improved progression-free survival versus standard triplet therapy.
*Randomized controlled trial; Level 2 (OCEBM).
Citation
Mina R, Beksac M, Rodríguez-Otero P, et al. Talquetamab–Daratumumab in Relapsed or Refractory Myeloma. N Engl J Med. 2026;395:671-683.
Background
Relapsed or hard-to-treat multiple myeloma often becomes resistant to existing drug classes. Talquetamab activates T cells against a different myeloma target, offering a possible earlier-line option.
Patients
864 adults with relapsed or refractory multiple myeloma after at least one prior treatment including lenalidomide and a proteasome inhibitor. Exclusions included anti-CD38-refractory disease, prior pomalidomide, and prior GPRC5D-directed therapy.
Intervention
Talquetamab plus daratumumab and pomalidomide, or talquetamab plus daratumumab.
Control
Daratumumab plus pomalidomide and dexamethasone.
Outcome
Primary: progression-free survival. Secondary: response, deep complete response, no measurable remaining disease, survival, and safety.
Follow-up Period
Median 24.6 months.
Results
| Outcome | Talquetamab + daratumumab + pomalidomide vs control | Talquetamab + daratumumab vs control |
|---|---|---|
| Progression or death | HR 0.28 (95% CI 0.20 to 0.40); 24-month survival without progression 81.3% vs 51.2%; NNT 4 | HR 0.33 (95% CI 0.24 to 0.46); 77.6% vs 51.2%; NNT 4 |
| Overall response | RR 1.14 (95% CI 1.06 to 1.23); NNT 10 | RR 1.14 (95% CI 1.06 to 1.23); NNT 10 |
| Complete response or better | RR 2.07 (95% CI 1.74 to 2.46); NNT 3 | RR 2.01 (95% CI 1.68 to 2.39); NNT 3 |
Analyses used intention-to-treat for effectiveness. Overall survival numerically favored talquetamab, but did not meet the prespecified interim threshold.
Limitations
Open-label design, interim analysis, industry sponsorship, and no formal comparison between the two talquetamab regimens. Results may not apply to anti-CD38-refractory patients.
Funding
Johnson & Johnson; relevant industry bias concern.
Clinical Application
Consider talquetamab combinations for eligible relapsed myeloma patients; monitor closely for infections, low neutrophils, taste changes, weight loss, and neurologic symptoms.
Discussion
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In this open-label phase 3 RCT, should talquetamab plus daratumumab (with or without pomalidomide) replace DPd for relapsed/refractory myeloma given improved 24-month PFS (81.3%/77.6% vs 51.2%; HR 0.28/0.33), and how do validity, toxicity, and applicability affect practice change? In this randomized trial, the hazard ratio for progression or death with Tal-DP versus DPd was 0.28. Which interpretation is most appropriate?