Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial
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.
Article Details
Authors (51)
Aurore Perrot
Cyrille Touzeau
Jérôme Lambert
Biostatistics and Medical Information Department, Hôpital St. Louis, Paris
Cyrille Hulin
Service d’Hématologie, Hôpital Haut Lévêque, Centre Hospitalier Universitaire (CHU) de Bordeaux, Pessac, France
Denis Caillot
6Department of Hematology, Centre Hospitalier Universitaire Dijon, Hôpital Du Bocage, Dijon, France
Lionel Karlin
Service Hématologie, Hôpital Universitaire Lyon Sud, Pierre-Bénite, France
Bertrand Arnulf
Hôpital Universitaire St. Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris
Philippe Rey
Centre Léon Bérard, Lyon, France
Laurent Garderet
Service Hématologie, Hôpital Universitaire Pitié-Salpêtrière, AP-HP, Paris
Margaret Macro
Service Hématologie, Institut Hématologie de Basse Normandie, Hôpital Universitaire de Caen, Caen, France
Martine Escoffre Barbe
11Department of Hematology, Hôpital Universitaire de Rennes, Rennes, France
Julie Gay
Hôpital de Bayonne, Bayonne, France
Thomas Chalopin
Romain Gounot
Service Hématologie, Hôpital Henri Mondor, Créteil, France
Jean-Marc Schiano
Service Hématologie, Institut Paoli-Calmettes, Marseille, France
Mourad Tiab
15CH Vendee, La Roche Sur Yon, France
Mohamad Mohty
Frederique Kuhnowski
18Department of Hematology, Institut Curie, Paris, France
Jean Fontan
17Department of Hematology, Centre Hospitalier Besançon, Besançon, France
Salomon Manier
Frédérique Orsini-Piocelle
11Department of Hematology, Centre Hospitalier Annecy Genevois, Epagny Metz-Tessy, France
Laure Vincent
11Department of Hematology, Montpellier University Hospital, Montpellier, France
Sophie Rigaudeau
12CH Versailles, Versailles, France
Xavier Leleu
Service Hématologie, Hôpital Universitaire de Poitiers, Poitiers, France
Benjamin Hebraud
2Institut Universitaire du Cancer, CHU Toulouse, Toulouse, France
Laurent Flet
Jean-Valère Malfuson
24Hôpital d'Instruction des Armées Percy, Clamart, Clamart, France
Caroline Jacquet
13CHU de Nancy, Hematology, Nancy, France
Driss Chaoui
15CH Argenteuil, Argenteuil, France
Nathalie Meuleman
7Jules Bordet Institute, Hematology Department, Brussels, Belgium
Wajed Abarah
30Department of Hematology, Grand Hôpital de l’Est Francilien, Meaux, France
Lydia Montes
24Department of Hematology, Centre Hospitalo-Universitaire de Amiens, Amiens, France
Riad Benramdane
29CH Cergy Pontoise, Cergy Pontoise, France
Cecile Sonntag
33Department of Hematology, Institut de Cancerologie Strasbourg, Strasbourg, France
Hacene Zerazhi
9centre Hospitalier d'Avignon, Avignon, France
Alina Danu
35Department of Hematology, Institut Gustave Roussy, Villejuif, France
Olivier Allangba
8Centre Hospitalier Yves Le Foll, Saint-Brieuc, France
Mamoun Dib
16Department of Hematology, Centre Hospitalo-Universitaire de Angers, Angers, France
Murielle Roussel
9Department of Hematology, Centre Hospitalo-Universitaire de Limoges, Limoges, France
Sophie Cereja
39Department of Hematology, Hôpital Sud Francilien, Corbeil Essonnes, France
Julien Depaus
40Department of Hematology, Hôpital de Namur, Namur, Belgium
Nicolas Branche
41Department of Hematology, Hôpital Universitaire de Nîmes, Nîmes, France
Hélène Demarquette
36Department of Hematology, Centre Hospitalier Dunkerque, Dunkerque, France
Valentine Richez
27Département de Hématologie, Centre Hospitalo-Universitaire de Nice, Nice, France
Brieuc Cherel
44Department of Hematology, Hôpital de Vannes, Vannes, France
Laurent Frenzel
Marie-Christiane Vekemans
23Department of Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Noemie Bigot
1APHP, Université Paris Cité, INSERM UMR 1342, Immno-hematologie, Paris, France
Hervé Avet-Loiseau
Unité Génomique du Myélome, Hôpital Universitaire de Toulouse Oncopole, Université de Toulouse, Toulouse, France
Jill Corre
Unité Génomique du Myélome, Hôpital Universitaire de Toulouse Oncopole, Université de Toulouse, Toulouse, France
Philippe Moreau