2 research outputs found
In silico and Functional Studies for Classification of EPAS1/HIF2A Genetic Variants Identified in Patients with Erythrocytosis
Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial
International audienceCD38-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 65â79âyears, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10 â5 by next-generation sequencing at 18âmonths from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10 â5 were reported in 35 patients (26%, 95% confidence interval (CI) 19â34) in IsaRd versus 71 (53%, 95% CI 44â61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89â5.28, P <â0.0001). The MRD benefit was consistent across subgroups at 10 â5 and 10 â6 , and was already observed at month 12. The proportion of patients with complete response or better at 18âmonths was higher with Isa-VRd (58% versus 33%; P <â0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P =â0.0003). At a median follow-up of 23.5âmonths, 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 â5 , 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: NCT0475187