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
Mené dans 14 pays sur 737 patients atteints d'un myélome multiple récemment diagnostiqué, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du daratumumab à un traitement combinant lénalidomide et dexaméthasone
Background : In the primary analysis of the phase 3 MAIA trial (median follow-up 28·0 months),a significant improvement in progression-free survival was observed with daratumumabplus lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone intransplantation-ineligible patients with newly diagnosed multiple myeloma. Here, wereport the updated efficacy and safety results from a prespecified interim analysisfor overall survival. Methods : MAIA is an ongoing, multicentre, randomised, open-label, phase 3 trial that enrolledpatients at 176 hospitals in 14 countries across North America, Europe, the MiddleEast, and the Asia-Pacific region. Eligible patients were aged 18 years or older,had newly diagnosed multiple myeloma, had an Eastern Cooperative Oncology Group performancestatus score of 0–2, and were ineligible for high-dose chemotherapy with autologousstem-cell transplantation because of their age (≥65 years) or comorbidities. Patientswere randomly assigned (1:1) using randomly permuted blocks (block size 4) by an interactiveweb response system to receive 28-day cycles of intravenous daratumumab (16 mg/kg,once per week during cycles 1–2, once every 2 weeks in cycles 3–6, and once every4 weeks thereafter) plus oral lenalidomide (25 mg on days 1–21 of each cycle) andoral dexamethasone (40 mg on days 1, 8, 15, and 22 of each cycle; daratumumab group)or lenalidomide and dexamethasone alone (control group). Randomisation was stratifiedby International Staging System disease stage, geographical region, and age. Neitherpatients nor investigators were masked to treatment assignment. The primary endpoint was progression-free survival, which was centrally assessed, and a secondary endpointwas overall survival (both assessed in the intention-to-treat population). The safetypopulation included patients who received at least one dose of the study treatment.The results presented here are from a prespecified interim analysis for overall survival,for which the prespecified stopping boundary was p=0·0414. This trial is registeredwith ClinicalTrials.gov, NCT02252172. Findings : Between March 18, 2015, and Jan 15, 2017, 952 patients were assessed for eligibility,of whom 737 patients were enrolled and randomly assigned to the daratumumab group(n=368) or the control group (n=369). At a median follow-up of 56·2 months (IQR 52·7–59·9),median progression-free survival was not reached (95% CI 54·8–not reached) in thedaratumumab group versus 34·4 months (29·6–39·2) in the control group (hazard ratio[HR] 0·53 [95% CI 0·43–0·66]; p<0·0001). Median overall survival was not reached ineither group (daratumumab group, 95% CI not reached–not reached; control group, 95%CI 55·7–not reached; HR 0·68 [95% CI 0·53–0·86]; p=0·0013). The most common (>15%)grade 3 or higher treatment-emergent adverse events were neutropenia (197 [54%] patientsin the daratumumab group vs 135 [37%] patients in the control group), pneumonia (70 [19%] vs 39 [11%]), anaemia (61 [17%] vs 79 [22%]), and lymphopenia (60 [16%] vs 41 [11%]). Serious adverse events occurred in 281 (77%) patients in the daratumumabgroup and 257 (70%) patients in the control group. Treatment-related deaths occurredin 13 (4%) patients in the daratumumab group and ten (3%) patients in the control group. Interpretation : Daratumumab plus lenalidomide and dexamethasone increased overall survival and progression-free survival in patients ineligible for stem-cell transplantation with newly diagnosedmultiple myeloma. There were no new safety concerns. Our results support the frontlineuse of daratumumab plus lenalidomide and dexamethasone for patients with multiplemyeloma who are ineligible for transplantation.
The Lancet Oncology 2021