Longitudinal assessments of minimal residual disease in high-risk patients from benefit phase 3 randomized Study of isatuximab plus lenalidomide and dexamethasone with bortezomib (Isa-VRd) versus isard in newly diagnosed transplant ineligible multiple myeloma. (IFM 2020-05)
Abstract
Abstract Introduction. A recent international genomic consensus staging has standardized the high-risk (HR) definition on the basis of an NGS-based definition plus serum beta-2-microglobulin level. Isa-VRd has become a standard-of-care for NDMM Transplant-Ineligible (TI). We studied the 12-24 months sustained MRD (sMRD) in high-risk patients using the genomic consensus staging in BENEFIT study. Methods. BENEFIT is a multicenter, phase 3 study, that randomized NDMM TI to receive Isa-VRd or IsaRd (ClinicalTrials.gov identifier: NCT04751877). Data are presented in intention-to-treat. IMS/IMWG new HR definition was assessed centrally by NGS on sorted plasma cells. Results. With a median follow-up of 33.4 months [95%CI, 33 - 34], 78 (29%) patients discontinued from the study, mostly for progressive disease. The HRMM (n=72, 27%) characterized 42/135 (31%) and 30/135 (22%) patients across Isa-VRd and IsaRd arms. The 18-month MRD negativity rate at 10-5, the primary end point, was similar across HRMM and non-HRMM within the same arm, and Isa-VRd remained superior for HRMM, OR 2.75 (95%CI, 1 to 7.5). Similar differences were observed at 10-6 at 18 months. The sustained MRD 12-24 months negativity rate at 10−5was higher for Isa-VRd than for IsaRd in HRMM, 31% and 13% respectively, OR 2.91 (95%CI, 0.8 to 10). There is no new safety signal observed across arms, including for HRMM. Conclusion. The results from the BENEFIT study continue to demonstrate meaningful benefit of the quadruplet-based Isa-VRd regimen in NDMM TI patients, including sMRD negativity rates. The benefits of the Isa-VRd regimen are observed in HRMM. This data supports Isa-VRd as a new SOC for NDMM TI aged of 65 to 79 patients, including for HRMM.
Article Details
Authors (41)
Anaïs Schavgoulidze
Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
Jérôme Lambert
Biostatistics and Medical Information Department, Hôpital St. Louis, Paris
Arthur Bobin
1CHU Poitiers, Poitiers, 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
Omar Benbrahim
7CHR Orleans, Orleans, France
Olivier Allangba
8Centre Hospitalier Yves Le Foll, Saint-Brieuc, France
Philippe Rey
Centre Léon Bérard, Lyon, France
Veronique Dorvaux
23CHR Metz, Metz, France
Marguerite Vignon
11Hematology Department, Cochin Hospital, AP-HP, Centre Paris-Cité University, Paris, France
Virginie Roland
21Department of Hematology, Centre Hospitalier Perpignan, Perpignan, France
Reda Garidi
13CH Saint Quentin, Saint Quentin, France
Jean-Noel Bastie
12University Hospital Dijon, Department of Clinical Hematology, Dijon, France
Marie-Lorraine Chretien
5Department of Hematology, Centre Hospitalo-Universitaire de Dijon, Dijon, France
Sophie Godet
15CHU Reims, Reims, France
Lydia Montes
24Department of Hematology, Centre Hospitalo-Universitaire de Amiens, Amiens, France
Cherel Brieuc
28CH Vannes, Vannes, France
Ikhlef Souhila
18Sorbonne University, Saint-Antoine Hôpital (AP-HP), Hematology, UMRs 938, Paris, France
Anne Vekkhof
18Sorbonne University, Saint-Antoine Hôpital (AP-HP), Hematology, UMRs 938, Paris, France
Thomas Chalopin
Bohrane Slama
3CH Avignon, Avignon, France
Laurent Frenzel
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
Aurelie Gontier
3Hematology, CIC 1082, U1313, CHU, University, Poitiers, Poitiers, France
Philippe Moreau
Thierry Facon
6Department of Hematology, University Hospital and INSERM Unité Mixte de Recherche S1277, Lille, France
Jill Corre
Unité Génomique du Myélome, Hôpital Universitaire de Toulouse Oncopole, Université de Toulouse, Toulouse, 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