In an interim analysis of a phase III trial (MonumenTAL-3) reported in The New England Journal of Medicine, Mina et al found that the combinations of talquetamab with daratumumab/pomalidomide (Tal-DP) and talquetamab plus daratumumab (Tal-D) improved progression-free survival vs daratumumab/pomalidomide and dexamethasone (DPd) in previously treated patients with relapsed or refractory myeloma.
Study Details
In the international open-label trial, 864 patients who had received at least one previous line of therapy were randomly assigned 1:1:1 between November 2022 and March 2025 to receive Tal-DP (n = 287), Tal-D (n = 287), or DPd (n = 290), with talquetamab and daratumumab given in 28-day cycles and DPd given according to established schedules. The primary endpoint was progression-free survival on independent review committee assessment in the intent-to-treat population.
Key Findings
At interim analysis (median follow-up = 24.6 months), progression-free survival at 24 months was 81.3% in the Tal-DP group (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.20–0.40, P < .001 vs DPd group), 77.6% in the Tal-D group (HR = 0.33, 95% CI = 0.24–0.46, P < .001 vs DPd group), and 51.2% in the DPd group.
For the Tal-DP and Tal-D group vs the DPd group, objective response rates were 88.2% and 88.5% vs 77.6% (both P < .001), with complete response or better in 71.1% and 69.0% vs 34.5% (both P < .001), and measurable residual disease–negative complete response rates were 52.3% and 46.3% vs 15.9% (P < .001).
Overall survival at 24 months was 89.2% in the Tal-DP group and 87.9% in the Tal-D group vs 79.1% in the DPd group (HR = 0.47, 95% CI = 0.30–0.73; HR = 0.51, 95% CI = 0.33–0.78).
Grade 3 or 4 adverse events occurred in 96.7% of the Tal-DP group, 78.8% of the Tal-D group, and 95.8% of the DPd group; the most common adverse events in all groups were hematologic. Grade 3 or 4 infection occurred in 37.7%, 29.2%, and 42.4% of patients, respectively. Serious adverse events occurred in 63.0%, 52.6%, and 53.7%. Cytokine-release syndrome of any grade occurred in 67.8% of the Tal-DP group (grade 1 or 2 in 67%), and immune effector cell–associated neurotoxicity syndrome of any grade was reported in 2.9% of the Tal-DP group (grade 3 in three patients) and 1.8% of the Tal-D group. Fatal adverse events occurred in 1.8%, 4.0%, and 4.6% of patients.
The investigators concluded: “Among patients with relapsed or refractory multiple myeloma who had previously received at least one line of therapy, both Tal-DP and Tal-D led to significantly longer progression-free survival than DPd.”
Peter M. Voorhees, MD, of Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, North Carolina, is the corresponding author for the New England Journal of Medicine article.
DISCLOSURE: The study was funded by Johnson & Johnson. For full disclosures of the study authors, visit nejm.org.
