Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial
Aurore Perrot, Cyrille Touzeau, Jérôme Lambert, Cyrille Hulin, D. Caillot, Lionel Karlin, Bertrand Arnulf, Philippe Rey, Laurent Garderet, Margaret Macro, Martine Escoffre‐Barbe, Julie Gay, Thomas Chalopin, Romain Gounot, Jean‐Marc Schiano de Colella, Mourad Tiab, Mohamad Mohty, Frédérique Kuhnowski, Jean Fontan, Salomon Manier, Frédérique Orsini Piocelle, Laure Vincent, Sophie Rigaudeau, Xavier Leleu, Benjamin Hébraud, Laurent Flet, Jean‐Valère Malfuson, Caroline Jacquet, Driss Chaoui, Nathalie Meuleman, Wajed Abarah, Lydia Montes, Riad Benramdane, Cécile Sonntag, Hacène Zerazhi, Alina Danu, Olivier Allangba, Mamoun Dib, Murielle Roussel, Sophie Cereja, Julien Depaus, Nicolas Branche, Hélène Demarquette, Valentine Richez, Brieuc Cherel, Laurent Frenzel, Marie‐Christiane Vekemans, Noémie Bigot, Hervé Avet‐Loiseau, Jill Corre, Philippe Moreau
Abstract
ABSTRACT: For patients with transplant-eligible newly diagnosed multiple myeloma, induction therapy with a quadruplet regimen before autologous transplant is the standard of care. The phase 3 IFM2020-02-MRD-adapted strategy (MIDAS) study assessed a minimal residual disease (MRD)-driven consolidation and maintenance strategy after induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD). We report safety and efficacy outcomes of six 28-day cycles of IsaKRD in 791 patients. The median age was 59 years; 13% had International Staging System (ISS) stage III, 5% Revised-ISS stage III, and 8% high-risk cytogenetics (Intergroupe Francophone du Myélome linear predictor cytogenetic score of >1). Overall, 96% (N = 757) of patients completed induction. The median CD34+ cell yield was 7 × 106/kg, with 94% of patients able to proceed with a potential tandem transplant. The best overall response rate was 95%. In the intent-to-treat population, 91% achieved a very good partial response or better after induction, with MRD-negativity rates of 63% at 10-5 and 47% at 10-6. During induction, 7 patients experienced disease progression, and 5 died due to disease progression (n = 1), cardiac events (n = 2), or other causes (n = 2). The most common grade 3/4 adverse events were neutropenia (25%), thrombocytopenia (5%), and infections (7%); only 13% of patients reported any grade peripheral neuropathy. IsaKRD induction yielded deep responses and high MRD-negativity rates while ensuring successful stem cell collection, with no new safety signals. Continued follow-up of this ongoing study is required to confirm these findings. This trial was registered at www.clinicaltrials.gov as #NCT04934475.