TY - JOUR
TI - A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma
AU - Mikhael, J.
AU - Richter, J.
AU - Vij, R.
AU - Cole, C.
AU - Zonder, J.
AU - Kaufman, J.L.
AU - Bensinger, W.
AU - Dimopoulos, M.
AU - Lendvai, N.
AU - Hari, P.
AU - Ocio, E.M.
AU - Gasparetto, C.
AU - Kumar, S.
AU - Oprea, C.
AU - Chiron, M.
AU - Brillac, C.
AU - Charpentier, E.
AU - San-Miguel, J.
AU - Martin, T.
JO - Leukemia Research
PY - 2020
VL - 34
TODO - 12
SP - 3298-3309
PB - Springer Nature BV
SN - 0145-2126
TODO - 10.1038/s41375-020-0857-2
TODO - bortezomib;  carfilzomib;  isatuximab;  lenalidomide;  monoclonal antibody;  pomalidomide;  proteasome inhibitor;  ADP ribosyl cyclase/cyclic ADP ribose hydrolase 1;  isatuximab;  monoclonal antibody, adult;  aged;  anaphylaxis;  anemia;  Article;  bronchospasm;  chill;  controlled study;  coughing;  cytogenetics;  diarrhea;  drug dose escalation;  drug efficacy;  drug safety;  drug tolerability;  dyspnea;  fatigue;  febrile neutropenia;  female;  gastroenteritis;  headache;  herpes zoster;  hot flush;  human;  immune response;  laboratory test;  major clinical study;  male;  meningococcemia;  monotherapy;  multicenter study;  multiple cycle treatment;  multiple myeloma;  nausea;  overall survival;  phase 2 clinical trial;  physical examination;  pneumonia;  prevalence;  priority journal;  progression free survival;  randomized controlled trial;  sepsis;  thorax pain;  treatment duration;  upper respiratory tract infection;  very elderly;  vomiting;  wheezing;  clinical trial;  metabolism;  middle aged;  multiple myeloma;  tumor recurrence, ADP-ribosyl Cyclase 1;  Adult;  Aged;  Aged, 80 and over;  Antibodies, Monoclonal, Humanized;  Female;  Humans;  Male;  Middle Aged;  Multiple Myeloma;  Neoplasm Recurrence, Local;  Progression-Free Survival
TODO - 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. © 2020, The Author(s).
ER -