Subcutaneous daratumumab plus carfilzomib and dexamethasone (D-Kd) versus carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma who received previous daratumumab treatment: LYNX study.

Daratumumab-based regimens demonstrate clinical efficacy in relapsed/refractory multiple myeloma (RRMM). As more patients receive frontline daratumumab-based therapy, evaluation of daratumumab retreatment is needed. In the phase 2 LYNX study (ClinicalTrials.gov Identifier: NCT03871829), 88 patients with RRMM who received 1-3 prior lines of therapy, one of which contained daratumumab, were randomized to receive subcutaneous daratumumab plus carfilzomib/dexamethasone (D-Kd; n = 44) or carfilzomib/dexamethasone (Kd; n = 44). The primary endpoint was the very good partial response or better (≥VGPR) rate. At the interim futility analysis, no significant differences in ≥ VGPR rates were found between treatment groups; therefore, the null hypothesis of no treatment difference was accepted, leading to study termination. At the final analysis, 45.5% of D-Kd patients and 40.9% of Kd patients achieved ≥ VGPR (odds ratio, 1.2 [90% CI, 0.59-2.46]; p = 0.6757). No new safety concerns were identified. Future studies are needed to optimize daratumumab-based regimens for patients with RRMM who have prior daratumumab exposure.