Unite de Genomique du Myelome, IUC-T Oncopole, Toulouse, France
Herve Avet-Loiseau , Philippe Moreau , Michel Attal , Cyrille Hulin , Bertrand Arnulf , Jill Corre , Laurent Garderet , Lionel Karlin , Jérôme Lambert , Margaret Macro , Aurore Perrot , Pieter Sonneveld , Mark-David Levin , Saskia Klein , Christopher Chiu , Lixia Pei , Carla De Boer , Tobias Kampfenkel , Soraya Wuilleme , Marie-Christine Béné
Background: In TE NDMM patients (pts), the CD38 monoclonal antibody DARA significantly reduced the risk of progression/death and improved stringent CR, ≥CR, and MRD-negative rates when added to VTd in the phase 3 CASSIOPEIA study. MRD status and its association with progression-free survival (PFS) was evaluated in TE NDMM pts receiving D-VTd vs VTd as pre-transplant induction/post-transplant consolidation in Part 1 of CASSIOPEIA. Methods: In Part 1, TE NDMM pts were randomized 1:1 to 4 cycles of pre-ASCT induction and 2 cycles of post-ASCT consolidation with DARA + VTd or VTd. Landmark analyses of MRD were performed on bone marrow aspirates after induction by multiparametric flow cytometry (MFC; 10–5 sensitivity threshold) and after consolidation (at Day 100 post-ASCT) by MFC (10–5) and next-generation sequencing (NGS; 10–6) for all pts, regardless of response. Results: A cohort of 1085 pts was randomized (D-VTd, n = 543; VTd, n = 542). Post-induction and post-consolidation MRD-negative rates were significantly higher for D-VTd vs VTd (Table). Post-consolidation MRD-negative rates (MFC) were consistent across pt subgroups, including ISS stage III or high-risk cytogenetics. Multivariate analyses accounting for treatment arm and MRD negativity (MFC) showed a PFS benefit in pts reaching MRD negativity (HR, 0.31; 95% CI, 0.20-0.50; P<0.0001). Based on these analyses, D-VTd showed additional PFS benefit vs VTd (HR, 0.48; 95% CI, 0.30-0.78; P = 0.0028). Analysis of MRD based on response (per IMWG criteria) will be presented. Conclusions: Adding DARA to VTd induction and consolidation deepened responses, as demonstrated by significant increases in MRD-negative rates. MRD negativity was associated with a PFS benefit regardless of treatment group. However, deepened responses with D-VTd led to improved outcomes, with MRD negativity associated with prolonged PFS, versus VTd in pts with TE NDMM. Clinical trial information: NCT02541383
D-VTd, % | VTd, % | P | |
---|---|---|---|
Post-induction | |||
MFC, 10–5 | 34.6 | 23.1 | <0.0001 |
Post-consolidation | |||
MFC, 10–5 | 63.7 | 43.5 | <0.0001 |
NGS, 10–6,a | 39.1 | 22.8 | <0.0001 |
aNGS MRD-evaluable population.
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Abstract Disclosures
2019 ASCO Annual Meeting
First Author: Philippe Moreau
2020 ASCO Virtual Scientific Program
First Author: Stefania Oliva
2023 ASCO Annual Meeting
First Author: Sagar Lonial
2021 ASCO Annual Meeting
First Author: Philippe Moreau