Sustained minimal residual disease (sMRD) negativity in transplant ineligible newly diagnosed multiple myeloma treated with isatuximab plus lenalidomide and dexamethasone with bortezomib (Isa-VRd) versus isa-rd: 12-24-month data from the phase 3 benefit trial (IFM 2020-05)
Abstract
Abstract Introduction. Sustained minimal residual disease (sMRD) negativity has shown a stronger correlation with survival outcomes than MRD negativity at a single time point or at best response. We evaluated MRD negativity between 12 and 24 months in newly diagnosed multiple myeloma (NDMM) transplant-ineligible (TI) patients enrolled in the BENEFIT study. Methods. BENEFIT is a multicenter, phase 3 randomized trial comparing isatuximab-lenalidomide-dexamethasone with or without bortezomib (Isa-Rd ± V) in NDMM TI patients. In the Isa-VRd arm, bortezomib (V) was administered weekly for up to 18 months, dexamethasone was permanently discontinued after 12 months, and isatuximab-lenalidomide (Isa-R) was continued until progression. Data are presented in the intention-to-treat (ITT) population. Results.With a median follow-up of 33.4 months (95% CI, 33.0–34.0), 78 patients (29%) discontinued treatment, primarily due to progressive disease. At 24 months, the MRD negativity rate at 10⁻⁵ was significantly higher in the Isa-VRd arm (odds ratio [OR] 2.26; 95% CI, 1.35–3.79; p=0.002). Sustained MRD negativity at 10⁻⁵ was also more frequent in the Isa-VRd arm (OR 2.73; 95% CI, 1.50–4.80; p=0.0007). Similar results were observed for sMRD at the 10⁻⁶ threshold. Importantly, MRD negativity at both 10⁻⁵ and 10⁻⁶ was evaluated in the t(11;14) NDMM TI subgroup. In this subgroup, MRD negativity rates were consistently lower at all time points up to 24 months, consistent with recent observations from the MIDAS study. Due to the small number of patients per group, no subgroup-specific analysis was feasible. Larger cohorts are required to determine whether t(11;14) MM in TI patients achieves delayed or less frequent MRD negativity, potentially reflecting a MGUS-like phenotype. No new safety signals were observed in either treatment arm, including in high-risk multiple myeloma (HRMM) patients. Conclusion. The BENEFIT study continues to support the efficacy of the quadruplet Isa-VRd regimen in NDMM TI patients, notably through improved sustained MRD negativity rates. These data support Isa-VRd as a new standard of care (SOC) for NDMM TI patients aged 65–79 years, including those with HRMM. ClinicalTrials.gov Identifier: NCT04751877
Article Details
Authors (38)
Arthur Bobin
1CHU Poitiers, Poitiers, France
Jérôme Lambert
Biostatistics and Medical Information Department, Hôpital St. Louis, Paris
Jill Corre
Unité Génomique du Myélome, Hôpital Universitaire de Toulouse Oncopole, Université de Toulouse, Toulouse, France
Salomon Manier
Aurore Perrot
Lionel Karlin
Service Hématologie, Hôpital Universitaire Lyon Sud, Pierre-Bénite, France
Murielle Roussel
9Department of Hematology, Centre Hospitalo-Universitaire de Limoges, Limoges, France
Noemie Bigot
1APHP, Université Paris Cité, INSERM UMR 1342, Immno-hematologie, Paris, France
Kamel Laribi
13CH du mans, Le Mans, France
Claire Dingremont
8CH Tarbes, Tarbes, France
Christophe Roul
35Department of Hematology, Centre Hospitalier La Rochelle, La Rochelle, France
Valentine Richez
27Département de Hématologie, Centre Hospitalo-Universitaire de Nice, Nice, France
Clara Mariette
Service Hématologie, Hôpital CHU de Grenoble, Grenoble, France
Sophie Rigaudeau
12CH Versailles, Versailles, France
Claire Calmettes
30Department of Hematology, Centre Hospitalier Périgueux, Périgueux, France
Mamoun Dib
16Department of Hematology, Centre Hospitalo-Universitaire de Angers, Angers, France
Mourad Tiab
15CH Vendee, La Roche Sur Yon, France
Laure Vincent
11Department of Hematology, Montpellier University Hospital, Montpellier, France
Jacques Delaunay
17Hopital Le Confluent, Nantes, France
Jean Pierre Marolleau
1EA4666 HEMATIM, UPJV, Amiens, France
Pascal Godmer
19CH Vannes, vannes, France
Anaïs Schavgoulidze
Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
Laurent Frenzel
Ronan Le Calloch
20CH Quimper, Quimper, France
Emilie Chalayer
33Department of Hematology, Centre Hospitalo-Universitaire de Saint-Etienne, Saint-Etienne, France
Helene Gardeney
1CHU Poitiers, Poitiers, France
Magaret Macro
16CHU Caen, Caen, France
Bruno Royer
2APHP, Paris, France
Stephanie Harel
1APHP, Université Paris Cité, INSERM UMR 1342, Immno-hematologie, Paris, France
Olivier Decaux
4Department of Hematology, Rennes University Hospital, Rennes, France
Bertrand Arnulf
Hôpital Universitaire St. Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris
Karim Belhadj Merzoug
12Department of Hematology, Hopital Mondor, APHP, Creteil, France
Cyrille Touzeau
Mohamad Mohty
Philippe Moreau
Thierry Facon
6Department of Hematology, University Hospital and INSERM Unité Mixte de Recherche S1277, Lille, France
Cyrille Hulin
Service d’Hématologie, Hôpital Haut Lévêque, Centre Hospitalier Universitaire (CHU) de Bordeaux, Pessac, France
Xavier Leleu
Service Hématologie, Hôpital Universitaire de Poitiers, Poitiers, France