OA – 52: Isatuximab plus lenalidomide and dexamethasone with bortezomib versus isatuximab plus lenalidomide and dexamethasone in newly diagnosed transplant ineligible Multiple Myeloma: The BENEFIT study.
Head of Myeloma Clinic and Head of Department of Haematology Hospital La Mileterie, Poitiers, France Poitiers, France
Introduction: CD38 targeting immunotherapy is approved in combination with lenalidomide and dexamethasone (DRd) in NDMM TI and considered the best standard of care. To improve current standard of care, we evaluated the added value of lite weekly bortezomib (V) to Isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd).
Methods: This IFM phase 3 study randomized newly diagnosed multiple myeloma patients, 65-79 years old, nonfrail, transplant ineligible, to IsaRd versus Isa-VRd arm. The primary endpoint was minimal residual disease negative rate at 10-5 by next generation sequencing at 18 months from randomization.
Results: At a median follow-up of 23.5 months, the 18-month MRD negative rates at 10-5 were reported in 35 patients (26%, CI95% 19-34) in IsaRd versus 71 (53%, 95%CI 44-61) in Isa-VRd [OR 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 observed from month 12 months. The proportion of patients with ≥CR at 18 months was significantly higher with Isa-VRd than IsaRd (58% vs. 33%; p< 0.0001), as was the proportion of patients with MRDand ≥CR (37% vs. 17%; p=0.0003). There was no difference yet observed for survival times. The addition of lite bortezomib did not significantly affect relative dose intensity of IsaRd.
Conclusions: Isa-VRd significantly increased MRD end points, including the 18-month negative rate at 10-5 , the primary end point, compared to IsaRd. This study proposes Isa-VRd as a new standard of care for NDMM TI non-frail patients.
