Talquetamab Plus Daratumumab Earns CHMP Backing in R/R Myeloma

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the indication for talquetamab (Talvey) to include its use in combination with daratumumab (Darzalex), with or without pomalidomide (Pomalyst), in adult patients with relapsed or refractory multiple myeloma previously treated with at least 1 line of therapy.¹

The positive opinion rests on findings from the phase 3 MonumenTAL-3 trial (NCT05455320). At the preplanned interim analysis, talquetamab combined with daratumumab and pomalidomide (Tal-DP; n = 287) cut the risk of progression or death by 72% vs daratumumab, pomalidomide, and dexamethasone (DPd; n = 290; HR, 0.28; 95% CI, 0.20-0.40; P < .0001).^1-3

With talquetamab plus daratumumab (Tal-D; n = 287), the corresponding risk reduction was 67% vs DPd (HR, 0.33; 95% CI, 0.24-0.46; P < .0001). After a median follow-up of 24.6 months, 81.3% (95% CI, 75.8-85.7) of patients in the Tal-DP arm and 77.6% (95% CI, 71.7-82.5) of those in the Tal-D arm were alive and progression free at 24 months, compared with 51.2% (95% CI, 44.8-57.1) in the DPd arm; median progression-free survival (PFS) had not been reached in either talquetamab arm vs 24.4 months with DPd.

"MonumenTAL-3 demonstrated significant improvements in PFS, overall survival [OS], response rates and depth of response with the combination of talquetamab and daratumumab," Ester in 't Groen, head of the haematology therapeutic area for Europe, the Middle East, and Africa at Johnson & Johnson, stated in a news release.¹ "For patients facing their first relapse, this combination has the potential to provide deep responses and keep their disease under control for longer at a critical point in their treatment journey."

How was the MonumenTAL-3 trial designed?

Between November 4, 2022, and March 13, 2025, investigators enrolled 864 patients in the randomized, open-label phase 3 study and randomly assigned them in a 1:1:1 ratio to Tal-DP, Tal-D, or DPd.² Patients were eleigible if they had measurable relapsed/refractory disease and had received 1 or more prior lines of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor. An ECOG performance status of 0 to 2 was also required. The study excluded patients with anti-CD38 monoclonal antibody–refractory disease, as well as those exposed to a GPRC5D-targeted agent, pomalidomide, or a T-cell–redirecting therapy in the 3 months preceding randomization.

Patients received subcutaneous talquetamab using step-up doses of 0.01, 0.06, and 0.4 mg/kg before moving to 0.8 mg/kg every 2 weeks. Subcutaneous daratumumab 1800 mg was given weekly during cycles 1 and 2, every 2 weeks during cycles 3 through 6, and every 4 weeks thereafter. In the Tal-DP arm, pomalidomide 2 mg was given once daily on days 1 through 21 beginning in cycle 2. Patients in the DPd arm received pomalidomide 4 mg daily on days 1 through 21. Dexamethasone premedication was mandatory in the talquetamab arms only during the first 2 weeks.

PFS by blinded independent review committee assessment per International Myeloma Working Group criteria served as the primary end point. Overall response rate (ORR), complete response (CR) or better rate, measurable residual disease (MRD)–negative complete response, and OS were key secondary end points, and safety was an additional secondary end point.

What other data supported the CHMP recommendation?

OS data also favored both talquetamab-based regimens over DPd, with an HR for death of 0.47 (95% CI, 0.30-0.73; P = .0006) for Tal-DP and 0.51 (95% CI, 0.33-0.78; P = .0015) for Tal-D. At 24 months, OS rates reached 89.2% with Tal-DP, 87.9% with Tal-D, and 79.1% with DPd.

ORRs were 88.2% and 88.5% in the Tal-DP and Tal-D arms, respectively, compared with 77.6% in the DPd arm. The 3 arms produced CR or better rates of 71.1%, 69.0%, and 34.5%, respectively, and MRD-negative CR rates (10⁻⁵ threshold by next-generation sequencing) of 52.3%, 46.3%, and 15.9% (P < .001 for all comparisons).^1,2

What is the safety profile of talquetamab plus daratumumab?

Rates of grade 3/4 treatment-emergent adverse effects (AEs) were 94.9% with Tal-DP, 74.8% with Tal-D, and 91.5% with DPd.¹ Serious AEs affected 63.0%, 52.6%, and 53.7% of patients in the respective arms, and grade 5 AEs occurred in 1.8%, 4.0%, and 4.6%.^1,2

Any-grade infections were reported in 87.3% of the Tal-DP arm, 84.3% of the Tal-D arm, and 83.0% of the DPd arm, with grade 3/4 infections in 37.7%, 29.2%, and 42.2%, respectively.¹ AEs led to treatment discontinuation at respective rates of 10.5%, 8.0%, and 6.7%.

"This off-the-shelf, immunotherapy-based combination leverages the power of our portfolio by bringing together talquetamab with the well-established therapy of daratumumab. By simultaneously targeting GPRC5D and CD38, our goal is to deliver deeper and longer lasting responses for patients," Yusri Elsayed, MD, MHSc, PhD, head of the global oncology therapeutic area at Johnson & Johnson, added in a news release.¹

References

1. CHMP recommends approval of Johnson & Johnson's Talvey (talquetamab) plus daratumumab in earlier line treatment of relapsed/refractory multiple myeloma. News release. Johnson & Johnson. October 16, 2026. Accessed October 16, 2026. https://www.globenewswire.com/news-release/2026/10/16/3382468/0/en/chmp-recommends-approval-of-johnson-johnson-s-talvey-talquetamab-plus-daratumumab-in-earlier-line-treatment-of-relapsed-refractory-multiple-myeloma.html
2. Mina R, Beksac M, Rodríguez-Otero P, et al; MonumenTAL-3 Investigators. Talquetamab-daratumumab in relapsed or refractory myeloma. N Engl J Med. 2026;395(7):671-683. doi:10.1056/NEJMoa2604657
3. Voorhees PM. Phase 3, randomized study of talquetamab (Tal) plus daratumumab (Dara) ± pomalidomide (Pom) vs Dara plus Pom and dexamethasone (DPd) in relapsed/refractory multiple myeloma (RRMM): MonumenTAL-3. Presented at: 2026 European Hematology Association Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S100.