• Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial

      Facon, Thierry; Kumar, Shaji; Plesner, Torben; Orlowski, Robert Z.; Moreau, Philippe; Bahlis, Nizar; Basu, Supratik; Nahi, Hareth; Hulin, Cyrille; Quach, Hang; et al. (Elsevier, 2021-10-13)
      Background At the primary analysis of the phase 3 MAIA study (median follow-up, 28·0 months), significant progression-free survival benefit was observed with daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed myeloma. We report updated efficacy and safety results from a prespecified interim analysis for overall survival. Methods MAIA is an ongoing, multicentre, randomised, open-label, phase 3 trial that enrolled patients between 18 March 2015 and 15 January 2017 at 176 sites in 14 countries. Eligible patients were aged ≥18 years, had newly diagnosed multiple myeloma, had an Eastern Cooperative Oncology Group performance status score of 0–2, and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation due to age (≥65 years) or comorbidities. Patients were randomised 1:1 by an interactive web response system to receive 28-day cycles of Rd with daratumumab (D-Rd group) or without (Rd group). Randomisation was stratified by International Staging System disease stage, geographic region, and age. Patients in both groups received oral lenalidomide (25 mg on days 1–21 of each cycle) and oral dexamethasone (40 mg on days 1, 8, 15, and 22 of each cycle). The D-Rd group also received intravenous daratumumab (16 mg/kg, once weekly during cycles 1–2, once every 2 weeks in cycles 3–6, and once every 4 weeks thereafter). The primary endpoint was progression-free survival, and a secondary endpoint was overall survival (both assessed in the intention-to-treat population). Results presented here are from a prespecified interim analysis for overall survival. ClinicalTrials.gov number, NCT02252172. Findings At a median follow-up of 56·2 months (interquartile range, 52·7–59·9), a significant benefit in overall survival was observed for the D-Rd group (hazard ratio [HR] 0·68; 95% CI 0·53–0·86; p=0·0013). The Kaplan-Meier estimate of the 60-month rate of overall survival was 66·3% (95% CI 60·8–71·3) in the D-Rd group and 53·1% (47·2–58·6) in the Rd group. Median progression-free survival in the D-Rd group versus the Rd group was not reached (95% CI 54·8–not reached) versus 34·4 months (95% CI 29·6–39·2; HR 0·53; 95% CI 0·43–0·66; p<0·0001). The most common (>15%) grade 3 or 4 treatment-emergent adverse events were neutropenia (197 [54%] patients in the D-Rd group and 135 [37%] patients in the Rd group), pneumonia (70 [19%] and 39 [11%]), anaemia (61 [17%] and 79 [22%]), and lymphopenia (60 [16%] and 41 [11%]). Serious adverse events occurred in 281 (77%) patients in the D-Rd group and 257 (70%) patients in the Rd group. Treatment-related deaths occurred in 13 (4%) patients in the D-Rd group and 10 (3%) patients in the Rd group (all due to adverse events). Interpretation D-Rd prolonged overall survival and progression-free survival in patients ineligible for stem-cell transplantation with newly diagnosed multiple myeloma. There were no new safety concerns.