EHA 2019: CASSIOPEIA Trial Examines Addition of Daratumumab to Standard Treatment Before and After ASCT in Multiple Myeloma
In the phase III CASSIOPEIA trial, reported in The Lancet and presented at the 24th Annual Congress of the European Hematology Association (EHA; Abstract S145) by Moreau et al, daratumumab plus bortezomib/thalidomide/dexamethasone (D-VTd) given before and after autologous stem cell transplantation (ASCT) improved the depth of response vs VTd alone in patients with newly diagnosed multiple myeloma.
In the open-label trial, 1,085 transplant-eligible patients from 111 European sites were randomly assigned between September 2015 and August 2017 to receive four pretransplant induction cycles and two posttransplant consolidation cycles of VTd alone (VTd group, n = 542) or in combination with daratumumab (D-VTd group, n = 543). The primary endpoint of part 1 of the trial, reported here, was stringent complete response assessed 100 days after transplantation. Part 2 of the trial (maintenance) is ongoing.
Stringent Complete Response
At day 100 after transplantation, stringent complete response was achieved in 29% of the D-VTd group and 20% of the VTd group in the intention-to-treat population (odds ratio = 1.60, P =. 0010). A complete response or better was achieved in 39% vs 26% (P < .0001).
Minimal residual disease–negativity (10−5 sensitivity threshold) was achieved in 64% vs 44% (P < .0001). Median progression-free survival from first randomization was not reached in either group; progression-free survival events occurred in 45 vs 91 patients (hazard ratio [HR] = 0.47, P < .0001). Death occurred on study in 14 vs 32 patients (HR = 0.43, 95% confidence interval = 0.23–0.80).
Adverse Events
The most common grade 3 or 4 adverse events in both the D-VTd and VTd groups included neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%). Grade 3 or 4 infections occurred in 22% vs 20%. Serious adverse events occurred in 47% vs 47% of patients, with the most common being neutropenia (4% vs 1%), pneumonia (4% vs 2%), pyrexia (3% vs 4%), and pulmonary embolism (1% vs 4%). Adverse events led to treatment discontinuation in 7% vs 8% of patients.
The investigators concluded, “D-VTd before and after autologous stem cell transplantation improved depth of response and progression-free survival with acceptable safety. CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma.”
Philippe Moreau, MD, of the Service d’Hematologie Clinique, Nantes University Hospital Hotel-Dieu, is the corresponding author for The Lancet article.
Disclosure: The study was supported by The Intergroupe Francophone du Myelome and Dutch-Belgian Cooperative Trial Group for Hematology Oncology. For full disclosures of the study authors, visit thelancet.com.
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