A dose-finding phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma
Mikhael, J. (Autor de correspondencia); Richter, J. ; Vij, R.; Cole, C. ; Zonder, J.; Kaufman, J. L.; Bensinger, W.; Dimopoulos, M.; Lendvai, N.; Hari, P. ; Ocio, E. M.; Gasparetto, C.; Kumar, S. ; Oprea, C.; Chiron, M.; Brillac, C.; Charpentier, E.; San Miguel Izquierdo, Jesús
; Martin, T.
A Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with >= 3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38-85), 5 (2-14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg Q2W/Q4W, 10 mg/kg Q2W, and 20 mg/kg QW/Q2W, respectively. At doses >= 10 mg/kg, median progression-free survival and overall survival were 4.6 and 18.7 months, respectively, and the ORR was 40.9% (9/22) in patients with high-risk cytogenetics. CD38 receptor density was similar in responders and non-responders. The most common non-hematologic adverse events (typically grade <= 2) were nausea (34.0%), fatigue (32.0%), and upper respiratory tract infections (28.9%). Infusion reactions (typically with first infusion and grade <= 2) occurred in 51.5% of patients. In conclusion, isatuximab is active and generally well tolerated in heavily pretreated RRMM, with greatest efficacy at doses >= 10 mg/kg.