CASSIOPEIA Study: VTd +/- Daratumumab in Newly Diagnosed Multiple Myeloma

For patients who are newly diagnosed with multiple myeloma (NDMM) in Europe, eligible for transplantation, Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation were considered for a standard treatment regimen. The main objective of this study was to assess the impact of incorporating daratumumab into VTd before and after autologous stem-cell transplantation.

The CASSIOPEIA trial, a randomized, open-label, phase 3 study, enrolled 111 transplant-eligible patients with newly diagnosed multiple myeloma from European sites. Participants were randomly assigned in a 1:1 ratio. They received either four pre-transplant induction cycles and two post-transplant consolidation cycles with VTd alone (VTd group) or VTd in combination with daratumumab (D-VTd group). After transplantation, the primary endpoint of part 1 was the assessment of a stringent complete response within 100 days. The part 2 trial is currently ongoing, focusing on maintenance. A total of 1085 patients from 111 European sites were randomly assigned the VTd group (n=542) and D-VTd group (n=543) from September 22, 2015, to August 1, 2017. After 100 days following transplantation, it was found that 157 (29%) out of 543 patients in the D-VTd group and 110 (20%) out of 542 patients in the VTd considering the intention-to-treat population, had achieved a stringent complete response group (odds ratio 1·60, 95% CI 1·21-2·12, p=0·0010). Also, 211 (39%) in the D-VTd group vs. 141 (26%) in the VTd group attained a complete response or improved. And 346 (64%) out of 543 vs. 236 (44%) out of 542 achieved minimal residual disease-negativity (10-5 sensitivity threshold, assessed by multiparametric flow cytometry; both p<0·0001). The median progression-free survival (PFS) from the first randomization was not reached in either group (hazard ratio 0·47, 95% CI 0·33-0·67, p<0·0001). About 46 patient deaths were recorded (14 vs 32, 0·43, 95% CI 0·23-0·80). The most common adverse events were lymphopenia (17% vs 10%), neutropenia (28% vs 15%), and stomatitis (13% vs 16%). The study concluded that combining daratumumab with the VTd regimen before and after autologous stem-cell transplantation resulted in an improved depth of response and progression-free survival while maintaining acceptable safety. The study provided evidence of the clinical benefit of combining daratumumab with standard care for transplant-eligible patients with newly diagnosed multiple myeloma.

Source:https://pubmed.ncbi.nlm.nih.gov/31171419/

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02541383

Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, Béné MC, Broijl A, Caillon H, Caillot D, Corre J, Delforge M, Dejoie T, Doyen C, Facon T, Sonntag C, Fontan J, Garderet L, Jie KS, Karlin L, Kuhnowski F, Lambert J, Leleu X, Lenain P, Macro M, Mathiot C, Orsini-Piocelle F, Perrot A, Stoppa AM, van de Donk NW, Wuilleme S, Zweegman S, Kolb B, Touzeau C, Roussel M, Tiab M, Marolleau JP, Meuleman N, Vekemans MC, Westerman M, Klein SK, Levin MD, Fermand JP, Escoffre-Barbe M, Eveillard JR, Garidi R, Ahmadi T, Zhuang S, Chiu C, Pei L, de Boer C, Smith E, Deraedt W, Kampfenkel T, Schecter J, Vermeulen J, Avet-Loiseau H, Sonneveld P. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomized, open-label, phase 3 study. Lancet. 2019 Jul 6;394(10192):29-38. doi: 10.1016/S0140-6736(19)31240-1. Epub 2019 June 3. Erratum in: Lancet. 2019 Jun 14;: PMID: 31171419.