Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial - Centre de recherche Saint-Antoine - UMR S938
Journal Articles Nature Medicine Year : 2024

Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial

1 IRMETIST [Poitiers] - Ischémie reperfusion, métabolisme et inflammation stérile en transplantation [U 1313]
2 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
3 CIC 1402 - CIC Poitiers – Centre d'investigation clinique de Poitiers
4 CHU Bordeaux
5 SBIM - Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA)
6 AP-HP - Hopital Saint-Louis [AP-HP]
7 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
8 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
9 CHU Limoges
10 CHU Amiens-Picardie
11 CHBA - Centre hospitalier Bretagne Atlantique (Morbihan)
12 CHU Trousseau [Tours]
13 Centre Hospitalier Henri Duffaut (Avignon)
14 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
15 Centre Hospitalier Le Mans (CH Le Mans)
16 Centre Hospitalier de Bigorre [Tarbes]
17 Hopital Saint-Louis [La Rochelle]
18 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
19 CHV - Centre Hospitalier de Versailles André Mignot
20 CHP - CENTRE HOSPITALIER PÉRIGUEUX
21 CHU Angers - Centre Hospitalier Universitaire d'Angers
22 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
23 CHU Montpellier
24 Hôpital privé du Confluent [Nantes]
25 Centre hospitalier de Troyes
26 CHU Caen
27 GHICL - Groupement des Hôpitaux de l'Institut Catholique de Lille
28 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
29 CHCB - Centre Hospitalier de la Côte Basque
30 Hopital Privé Sévigné [Cesson-Sévigné, France]
31 Groupe Hospitalier du Havre
32 CHU Mont de Marsan
33 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
34 Hôpital Necker - Enfants Malades [AP-HP]
35 CHIC - Centre Hospitalier Intercommunal de Cornouaille
36 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
37 Hôpital Avicenne [AP-HP]
38 Centre Hopitalier Pierre Oudot [Bourgoin-Jallieu]
39 Médipôle De Savoie
40 Centre Hospitalier Chalon-sur-Saône William Morey
41 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
42 Université Paris-Saclay
43 HIA - Hopital d'instruction des armées Sainte-Anne [Toulon]
44 Centre Hospitalier Sud Francilien
45 CHU Nice - Centre Hospitalier Universitaire de Nice
46 HAL – CH Dunkerque - Hôpital Alexandra Lepève – Centre Hospitalier de Dunkerque
47 Centre Hospitalier de Lens
48 CHU Pitié-Salpêtrière [AP-HP]
49 CH E.Muller Mulhouse - Centre Hospitalier Emile Muller [Mulhouse]
50 MOBIDIC - Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer
51 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
52 Hôpital Henri Mondor
53 Hôtel-Dieu de Nantes
54 Nantes Univ - Nantes Université
55 CRSA - Centre de Recherche Saint-Antoine
56 CHU Saint-Antoine [AP-HP]
57 CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
58 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
Cyrille Hulin
  • Function : Author
Murielle Roussel
  • Function : Author
Lydia Montes
  • Function : Author
Laure Vincent
  • Function : Author
Margaret Macro
  • Function : Author
Reza Tabrizi
  • Function : Author
Selim Corm
  • Function : Author

Abstract

CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65–79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10 −5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10 −5 were reported in 35 patients (26%, 95% confidence interval (CI) 19–34) in IsaRd versus 71 (53%, 95% CI 44–61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89–5.28, P < 0.0001). The MRD benefit was consistent across subgroups at 10 −5 and 10 −6 , and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10 −5 , the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877

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Cancer
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hal-04614433 , version 1 (12-09-2024)

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Xavier Leleu, Cyrille Hulin, Jerome Lambert, Arthur Bobin, Aurore Perrot, et al.. Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial. Nature Medicine, 2024, 30 (8), pp.2235-2241. ⟨10.1038/s41591-024-03050-2⟩. ⟨hal-04614433⟩
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