As reported in The Lancet Oncology by Philippe Moreau, MD, and colleagues, long-term follow-up of the phase III CASSIOPEIA trial has shown improved progression-free survival with daratumumab maintenance vs observation both among newly diagnosed patients with transplant-eligible multiple myeloma who received pretransplantation induction and posttransplantation consolidation with daratumumab plus bortezomib, thalidomide, and dexamethasone (D-VTd) and those who received VTd.
Philippe Moreau, MD
Part 1 of the trial supported the approval of daratumumab plus VTd as induction and consolidation vs VTd on the basis of improved depth of response and prolonged progression-free survival.
Study Details
In part 1 of the European multicenter open-label trial, 1,085 patients were randomly assigned between September 2015 and August 2017 to receive pretransplantation induction and posttransplantation consolidation treatment with D-VTd (n = 543) or VTd (n = 542). In part 2 of the trial, patients in either group who completed consolidation and had a partial response or better were randomly assigned again to daratumumab maintenance at 16 mg/kg every 8 weeks (n = 442, including 229 from the D-VTd group and 213 from the VTd group) or observation (n = 444, including 229 from the D-VTd group and 215 from the VTd group) for up to 2 years. The primary outcome measure for part 2 was progression-free survival after second random assignment.
Key Findings
At the clinical cutoff in September 2023, median follow-up was 80.1 months (interquartile range [IQR] = 75.7–85.6 months) from first randomization and 70.6 months (IQR = 66.4–76.1 months) from second randomization.
Median progression-free survival from second randomization was not reached (95% confidence interval [CI] = 79.9 months to not estimable) in the daratumumab maintenance group vs 45.8 months (95% CI = 41.8–49.6 months) in the observation group (HR = 0.49, 95% CI = 0.40–0.59, P < .0001).
Median progression-free survival from second randomization was not reached (95% CI = 74.6 months to not estimable) in the D-VTd plus daratumumab maintenance group vs 72.1 months (95% CI = 52.8 months to not estimable) in the D-VTd plus observation group (HR = 0.76, 95% CI = 0.58–1.00, P = .048). Median progression-free survival was not reached (95% CI = 66.9 months to not estimable) in the VTd plus daratumumab maintenance group vs 32.7 months (95% CI = 27.2–38.7 months) in the VTd plus observation group (HR = 0.34, 95% CI = 0.26–0.44, P < .0001).
The investigators concluded: “The long-term follow-up results of CASSIOPEIA show that including daratumumab in both the induction and consolidation phase and the maintenance phase led to superior progression-free survival outcomes. Our results confirm D-VTd induction and consolidation as a standard of care and support the option of subsequent daratumumab monotherapy maintenance for transplant-eligible patients with newly diagnosed multiple myeloma.”
Dr. Moreau, of the Hematology Department, University Hospital Hotel-Dieu, Nantes, France, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the Intergroupe Francophone du Myélome, Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research & Development. For full disclosures of the study authors, visit thelancet.com.
