MM-339: Effect of Lenalidomide (R) ± Dexamethasone (d) Discontinuation on Daratumumab Efficacy in Multiple Myeloma (MM): Subgroup Analysis of the Phase 3 MAIA and POLLUX Studies

Context: Daratumumab (D), is approved as monotherapy and combination therapy for MM. We report an analysis of patients who discontinued R±d in the D-Rd arm of the MAIA and POLLUX studies. Design: In MAIA and POLLUX, patients with transplant-ineligible newly diagnosed MM and relapsed/refractory MM, respectively, were randomized (1:1) to Rd (R, 25 mg orally Days 1-21 of each 28-day cycle; d, 40 mg orally QW) ±D (16 mg/kg intravenously, QW Cycles 1-2, Q2W Cycles 3-6, then Q4W). The primary endpoint was progression-free survival (PFS). Landmark PFS analyses excluding events before 12- or 24-mo were conducted for all patients and by subgroups. Results: Patients were randomized in MAIA (D-Rd, n=368; Rd, n=369) and POLLUX (D-Rd, n=286; Rd, n=283). Median follow-up was 36.4 and 54.8 months, respectively. Among all randomized patients (ITT population), PFS rates were improved for D-Rd vs Rd in MAIA (NR vs 33.8 months; 36-month PFS rates, 68% vs 46%) and POLLUX (45.0 months vs 17.5 months; 60-month PFS rates, 44% vs 17%). Among D-Rd patients, 73 and 44 discontinued R in MAIA and POLLUX, respectively; 45 and 18 discontinued both R and d, and 28 and 26 discontinued R only but continued d. Most patients discontinuing R discontinued after 6 mo of treatment (MAIA, n=63; POLLUX, n=38), mostly due to adverse events (AEs). Median PFS for R discontinuers was NR in MAIA (36-mo PFS rate, 76%) and POLLUX (60-mo PFS rate, 62%). Landmark analysis for 12 mo and 24 mo showed median PFS was NR in MAIA for the ITT population, those discontinuing R, and those discontinuing R and d; PFS was NR in all patients and subgroups in POLLUX. In both studies, most responders achieved best response before R±d discontinuation. At the time of R discontinuation, many patients showed response rates in MAIA (≥complete response [CR], 45%; ≥very good partial response [VGPR], 90%) and POLLUX (≥CR, 73%; ≥VGPR, 91%) that were consistent with the ITT populations. Conclusions: In MAIA and POLLUX, patients in ≥VGPR who received D-Rd and discontinued R±d, but remained on daratumumab, demonstrated benefits in PFS and response comparable to the overall study populations.