A Phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma
Mené sur 57 patients atteints d'un myélome multiple récidivant ou réfractaire, cet essai de phase Ib évalue les caractéristiques pharmacocinétiques, la dose maximale tolérée, l'efficacité, du point de vue du taux de réponse globale, et la toxicité de l'isatuximab, un anticorps monoclonal anti-CD38, en combinaison avec le lénalidomide et la dexaméthasone
Isatuximab (anti-CD38 mAb) in combination with lenalidomide/dexamethasone is active in heavily pretreated relapsed/refractory myeloma. Overall, the safety profile of this combination is similar to the characteristic safety profiles of the individual agents This phase 1b, open-label, dose-escalation study (NCT01749969) assessed the safety, efficacy, and pharmacokinetics of anti-CD38 monoclonal antibody isatuximab given in two schedules (3, 5, 10 mg/kg every other week [Q2W] or 10, 20 mg/kg weekly for 4 weeks then Q2W thereafter [QW/Q2W]), in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg (weekly), in patients with relapsed/refractory multiple myeloma (RRMM). Patients received 28-day treatment cycles; the primary objective was to determine the maximum tolerated dose (MTD) of isatuximab with lenalidomide and dexamethasone. Fifty-seven patients (median five [range 1-12] prior regimens; 83% refractory to previous lenalidomide therapy) were treated. Median duration of dosing was 36.4 weeks; 15 patients remained on treatment at data cut-off. Isatuximab-lenalidomide-dexamethasone was generally well tolerated with only one dose-limiting toxicity reported (grade 3 pneumonia at 20 mg/kg QW/Q2W); the MTD was not reached. The most common isatuximab-related adverse events were infusion-associated reactions (IARs) (56%), which were grade 1/2 in 84% of patients who had an IAR and predominantly occurred during the first infusion. In the efficacy-evaluable population the overall response rate (ORR) was 56% (29/52), and was similar between the 10 mg/kg Q2W and 10 and 20 mg/kg QW/Q2W cohorts. The ORR was 52% in 42 evaluable lenalidomide-refractory patients. Overall median progression-free survival was 8.5 months. Isatuximab exposure increased in a greater than dose-proportional manner; isatuximab and lenalidomide pharmacokinetic parameters appeared independent. These data suggest that isatuximab combined with lenalidomide and dexamethasone is active and tolerated in heavily pretreated patients with RRMM.%U
Blood 2017