MonumenTAL-3: Talquetamab-based combinations for RRMM

Results from the randomized, multicenter, phase III MonumenTAL-3 trial (NCT05455320) evaluating talquetamab-containing combination regimens in patients with relapsed/refractory multiple myeloma (RRMM) were published in The New England Journal of Medicine by Mina et al. Patients (N = 864) who had previously received at least one line of therapy, including lenalidomide and a proteasome inhibitor, with no prior exposure to pomalidomide or G protein-coupled receptor class C group 5 member D (GPRC5D)-directed therapy, were randomly assigned 1:1:1 to receive talquetamab + daratumumab + pomalidomide (Tal-DP; n = 287), talquetamab + daratumumab (Tal-D; n = 287), or daratumumab + pomalidomide + dexamethasone (DPd; n = 290).

Key data: At a median follow-up of 24.6 months, the 24-month progression-free survival (PFS) rate was higher with Tal-DP and Tal-D than with DPd (81.3% and 77.6% vs 51.2%; hazard ratio [HR], 0.28 [95% confidence interval (CI), 0.20–0.40] and 0.33 [95% CI, 0.24–0.46]; p < 0.001 for both). The overall response rate (ORR) was higher with Tal-DP and Tal-D than with DPd (88.2% and 88.5% vs 77.6%; p < 0.001 for both). Complete response (CR) or better (≥CR) was achieved in 71.1%, 69.0%, and 34.5% of patients, while measurable residual disease (MRD)-negative CR at a sensitivity of 10^-5 was achieved in 52.3%, 46.3%, and 15.9%, respectively (p < 0.001 for both). The 24-month overall survival (OS) estimates were 89.2%, 87.9%, and 79.1%, respectively. Serious adverse events (SAEs) occurred in 63.0%, 52.6%, and 53.7% of patients in the Tal-DP, Tal-D, and DPd groups, respectively.

Key learning: Both Tal-DP and Tal-D resulted in prolonged PFS and higher rates of ≥CR and MRD-negative CR than DPd, supporting these combinations as additional treatment options for patients with RRMM who have received at least one prior line of therapy.