In a French phase III trial (IFM2017-03) reported in The Lancet Oncology, Manier et al found that a dexamethasone-sparing regimen of daratumumab plus lenalidomide improved progression-free survival vs lenalidomide plus dexamethasone in patients with frailty and newly diagnosed multiple myeloma.
Study Details
In the open-label multicenter trial, 295 patients aged 65 years or older with newly diagnosed disease and an Eastern Cooperative Oncology Group (ECOG) proxy frailty score of 2 or more were randomly assigned 2:1 between October 2019 and July 2021 to receive daratumumab at 1,800 mg plus lenalidomide at 25 mg daily for 21 days of a 28-day cycle, and dexamethasone at 20 mg weekly for two cycles (dexamethasone-sparing group; n = 200) or lenalidomide at 25 mg daily and dexamethasone at 20 mg weekly (control group; n = 95). The primary endpoint was progression-free survival.
Key Findings
Patients had a median age of 81 years (interquartile range [IQR] = 77–84 years), with 180 (61%) aged > 80 years. Median follow-up was 46.3 months (IQR = 46.0–52.7 months).
Median progression-free survival was 53.4 months (95% confidence interval [CI] = 35.3 months to not reached) in the dexamethasone-sparing group vs 22.5 months (95% CI = 16.5–39.0 months) in the control group (hazard ratio [HR] = 0.51, 95% CI = 0.37–0.70, P < .0001). Subgroup analysis showed superiority of lenalidomide plus daratumumab vs lenalidomide plus dexamethasone across most subgroups, including those defined by age, ECOG performance status, disease stage, and cytogenetic risk group.
Median time to next treatment was not reached (95% CI = not reached to not reached) in the lenalidomide plus daratumumab group vs 47.8 months (95% CI = 22.7 months to not reached) in the control group (HR = 0.45, 95% CI = 0.30–0.67, P < .0001).
Median overall survival was not reached (95% CI = not reached to not reached) in the dexamethasone-sparing group vs 47.3 months (95% CI = 36 months to not reached) in the control group (HR = 0.52, 95% CI = 0.35–0.77, P = .0010). Rates at 4 years were 68% vs 48%, respectively.
Grade ≥ 3 adverse events occurred in 89% of patients in the dexamethasone-sparing group vs 79% of the control group; the most common were neutropenia (55% vs 24%) and infection (19% vs 21%). Serious adverse events occurred in 63% vs 69% of patients. Adverse events led to discontinuation of all study treatment in 18% vs 24% of patients.
The investigators concluded: “In the IFM2017-03 trial, use of lenalidomide plus daratumumab, with dexamethasone limited to the first two treatment cycles, reduced the risk of progression or death compared with lenalidomide plus dexamethasone, with no additional safety concerns. Lenalidomide plus daratumumab could therefore be considered as a treatment option for older patients with frailty and newly diagnosed multiple myeloma.”
Salomon Manier, MD, PhD, of the Department of Hematology, University Hospital of Lille, Lille, France, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Johnson & Johnson. For full disclosures of all study authors, visit thelancet.com.
