Hematology, University Hospital Hôtel-Dieu, Nantes, France
Philippe Moreau , Michel Attal , Cyrille Hulin , Marie-Christine Béné , Annemiek Broijl , Denis Caillot , Michel Delforge , Thomas Dejoie , Thierry Facon , Jérôme Lambert , Xavier Leleu , Margaret Macro , Aurore Perrot , Sonja Zweegman , Tahamtan Ahmadi , Christopher Chiu , Lixia Pei , Jessica Vermeulen , Herve Avet-Loiseau , Pieter Sonneveld
Background: VTd is a standard of care (SoC) for TE NDMM. CD38 mAb DARA significantly reduced the risk of progression/death and improved CR and MRD-negative rates in relapsed refractory MM or transplant-ineligible NDMM in phase 3 studies. We report the primary and final analysis of Part 1 of CASSIOPEIA. Methods: In Part 1, TE NDMM pts 18-65 y were randomized 1:1 to VTd (6 28-day cycles [C; 4 pre-ASCT induction, 2 post-ASCT consolidation] of V 1.3 mg/m2 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/m2 was pre-ASCT HDT. The primary endpoint, post-consolidation sCR rate, was assessed at Day [D] 100 post-ASCT. Part 2 (maintenance) is ongoing.Results: A cohort of 1085 pts (D-VTd, 543; VTd, 542) was randomized. The D 100 post-ASCT sCR rate was significantly higher for D-VTd vs VTd (28.9% vs 20.3%; P = 0.0010; Table). At 18.8-mo median follow-up, PFS from first randomization favored D-VTd with HR 0.47 (95% CI, 0.33-0.67; P<0.0001). With median PFS NR in either arm, 18-mo PFS rates were 92.7% vs 84.6% for D-VTd vs VTd. Rates of ≥CR, ≥VGPR, and MRD negativity supported sCR results (Table). OS 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 TEAEs (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 pts. Conclusions: 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 TE NDMM. CASSIOPEIA is the first study to demonstrate clinical benefit of DARA + SoC in TE NDMM. Clinical trial information: NCT02541383
D-VTd, % | VTd, % | OR (95% CI) | P | |
---|---|---|---|---|
sCR | 28.9 | 20.3 | 1.60 (1.21-2.12) | 0.0010 |
≥CR | 38.9 | 26.0 | 1.82 (1.40-2.36) | <0.0001 |
≥VGPR | 83.4 | 78.0 | 1.41 (1.04-1.92) | 0.0239 |
MRD-negative (10–5) | 63.7 | 43.5 | 2.27 (1.78-2.90) | <0.0001 |
≥CR + MRD-negative (10–5) | 33.7 | 19.9 | 2.06 (1.56-2.72) | <0.0001 |
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Abstract Disclosures
2019 ASCO Annual Meeting
First Author: Cyrille Hulin
2023 ASCO Annual Meeting
First Author: Sagar Lonial
2020 ASCO Virtual Scientific Program
First Author: Cyrille Touzeau
2022 ASCO Annual Meeting
First Author: Paul G. Richardson