Type: Oral
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Refining the Evidence: Randomized Trials in Multiple Myeloma
Hematology Disease Topics & Pathways:
Adult, Combination therapy, Clinical Practice (Health Services and Quality), Drug development, Treatment Considerations, Human, Study Population
Methods. The IFM2017-03 trial is a prospective, randomized, open-label study done at 90 IFM centers. Patients with NDMM over the age of 65 and with an ECOG proxy frailty score ≥ 2 were randomized 1:2 to receive 28-day cycles of lenalidomide (25mg/day, 21/28) and dexamethasone (20mg QW) – Rd arm - or daratumumab (1800mg SC QW for 8 weeks, Q2W for 16 weeks and Q4W thereafter), lenalidomide (25mg/day, 21/28) and 2 cycles of dexamethasone (20mg QW for 8 weeks) – DR arm - until progression or unacceptable toxicity. Randomization was stratified on ISS and age. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall response rate, VGPR or better rate, overall survival (OS) and occurrence of grade 3 or more side effects.
Results. In total, 295 patients were randomized (200 in DR arm and 95 in Rd arm). Median age was 81 years (range 68-92) with 84% of patients over the age of 75 years and 61% over the age of 80 years. Baseline demographics and disease characteristics were well balanced between arms. At data cut-of, with a median follow-up time of 40 months (95%CI, 38.5 - 41.7), 79 (42%) and 16 (17%) patients in DR and Rd arms were still on treatment, respectively. Median treatment duration was 34.5 months (95%CI, 28.3 - 40.9) in arm DR and 14.3 months (95%CI, 10.8 - 20.6) in arm Rd. Overall best response rates were 92% in DR and 85% in Rd arms (p=0.025). Median PFS was 48.5 months (95%CI, 35,1-NR) in DR arm vs. 21.5 months (95%CI, 16.2-36.0) in Rd arm, HR 0.51 (95%CI, 0.37-0.71), log-rank p<0.0001 (Figure 1). PFS benefit was consistent across all subgroups defined by age, ECOG, Charlson, ISS, cytogenetics and creatinine clearance. Median OS was not reached in DR (95%CI, 53.4-NR) vs. 36.0 months in Rd, HR 0.46 (95%CI, 0.31–0.69), log-rank p=0.0001. At least one AE (grade ≥ 3) occurred in 88% and 77% of patients in DR and Rd arms, respectively. Patients in DR group had more grade ≥ 3 hematologic AE with neutropenia (DR 62%, Rd 33%) but similar grade ≥ 3 infections, with 18% in DR and 19% in Rd arms. Among patients with infections, 5% in DR and 7% in Rd had a pneumonia. Discontinuations due to AEs were similar in both arms (28% in DR and 34% in Rd). Baseline health-related quality of life (HRQoL) were well balanced between the 2 arms. The DR group had significantly shorter times to clinically meaningful improvement than Rd group in all QLQ-C30 domains.
Conclusion. The IFM2017-03 trial is the first phase 3 study dedicated to frail patients. It shows a significant reduced risk of progression or death by 49% in DR (dexamethasone-sparing regimen) vs. Rd, with a favorable safety profile and an improved HRQoL.
Disclosures: Manier: Takeda: Consultancy; Sanofi: Consultancy; Novartis: Consultancy; Janssen: Consultancy; GlaxoSmithKline: Consultancy; Celgene/BMS: Consultancy; Amgen: Consultancy; Adaptive Biotechnology: Consultancy; Roche: Consultancy; Regeneron: Consultancy; Abbvie: Consultancy. Karlin: AbbVie, Amgen, Celgene, Janssen, Sanofi, Takeda: Honoraria; Amgen, Celgene, GSK, Janssen, and Takeda: Other: Advisory role. Tabrizi: SANOFI: Honoraria. Perrot: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Menarini Stemline: Honoraria; Takeda: Honoraria, Research Funding; Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria. Moreau: Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Other: Participation on a Data Safety Monitoring Board or advisory board ; Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Honoraria; Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Consultancy. Leleu: Kite, A Gilead Company: Consultancy, Honoraria.
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