Open AccessS145 PHASE 3 RANDOMIZED STUDY OF DARATUMUMAB + BORTEZOMIB/THALIDOMIDE/DEXAMETHASONE (D‐VTD) VERSUS VTD IN TRANSPLANT‐ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: PART 1 CASSIOPEIA RESULTS
Author(s) -
Moreau P.,
Attal M.,
Hulin C.,
Arnulf B.,
Belhadj K.,
Benboubker L.,
Béné M. C.,
Broijl A.,
Caillon H.,
Caillot D.,
Corre J.,
Delforge M.,
Dejoie T.,
Doyen C.,
Facon T.,
Sonntag C.,
Garderet L.,
Jie K.S.,
Karlin L.,
Kuhnowski F.,
Lambert J.,
Leleu X.,
Lenain P.,
Macro M.,
OrsiniPiocelle F.,
Perrot A.,
Stoppa A.M.,
Donk N. W.,
Wuilleme S.,
Zweegman S.,
Kolb B.,
Touzeau C.,
Roussel M.,
Tiab M.,
Marolleau J.P.,
Meuleman N.,
Vekemans M.C.,
Westerman M.,
Klein S. K.,
Levin M.D.,
EscoffreBarbe M.,
Eveillard J.R.,
Garidi R.,
Ahmadi T.,
Zhuang S.,
Chiu C.,
Pei L.,
Vanquickelberghe V.,
Boer C.,
Smith E.,
Deraedt W.,
Kampfenkel T.,
Schecter J.,
Vermeulen J.,
AvetLoiseau H.,
Sonneveld P.
Publication year - 2019
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/01.hs9.0000558800.37954.72
Subject(s) - medicine , daratumumab , multiple myeloma , autologous stem cell transplantation , hazard ratio , lenalidomide , clinical endpoint , thalidomide , bortezomib , surgery , oncology , gastroenterology , randomized controlled trial , confidence interval
Background: VTd is a standard of care for transplant‐eligible newly diagnosed multiple myeloma (NDMM) patients. Daratumumab (DARA), a CD38 mAb, significantly reduced the risk of progression or death and improved complete response (CR) and minimal residual disease (MRD)‐negative rates in relapsed refractory multiple myeloma or transplant‐ineligible NDMM in phase 3 studies. Aims: We report the primary and final analysis of Part 1 of the CASSIOPEIA trial for NDMM. Methods: In Part 1, transplant‐eligible NDMM patients 18–65 years old were randomized 1:1 to VTd (6 28‐day cycles [C; 4 pre‐autologous stem cell transplantation {ASCT} induction, 2 post‐ASCT consolidation] of V 1.3 mg/m 2 SC BIW Week [W] 1–2; T 100 mg PO QD; d 40–80 mg/week PO or IV W 1‐4 C 1‐2, W 1‐3 C 3‐6) ± DARA (16 mg/kg IV QW C 1‐2, Q2W C 3‐6). Melphalan 200 mg/m 2 was pre‐ASCT therapy. The primary endpoint was the rate of post‐consolidation stringent complete response (sCR) assessed at Day 100 post‐ASCT. Part 2 (maintenance) is ongoing. Results: A cohort of 1085 patients (D‐VTd, 543; VTd, 542) was randomized. The Day 100 post‐ASCT sCR rate was significantly higher for the D‐VTd arm versus the VTd arm (28.9% vs 20.3%; P = 0.0010; Table). With 18.8‐months median follow‐up, progression‐free survival (PFS) from first randomization favored D‐VTd with a hazard ratio (HR) of 0.47 (95% CI, 0.33‐0.67; P < 0.0001; Figure). With median PFS not reached in either arm, 18‐month PFS rates were 92.7% versus 84.6% for D‐VTd versus VTd. Rates of ≥CR, ≥VGPR, and MRD negativity supported sCR results (Table). Overall survival is immature with 46 deaths on study (D‐VTd, 14; VTd, 32; HR, 0.43; 95% CI, 0.23–0.80). The most common (≥10%) grade 3/4 treatment‐emergent adverse events (D‐VTd/VTd) were neutropenia (27.6%/14.7%), lymphopenia (17.0%/9.7%), stomatitis (12.7%/16.4%), and thrombocytopenia (11.0%/7.4%). In the D‐VTd arm, infusion‐related reactions occurred in 35.4% of patients. Summary/Conclusion: D‐VTd in induction prior to and consolidation after ASCT improved depth of response (sCR, ≥CR, and MRD negativity) and PFS with acceptable safety. The favorable benefit‐risk profile supports the use of D‐VTd in transplant‐eligible NDMM. CASSIOPEIA is the first study to demonstrate the clinical benefit of daratumumab plus standard of care in transplant‐eligible NDMM patients.