@article{3077575,
    title = "A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma",
    author = "Mikhael, J. and Richter, J. and Vij, R. and Cole, C. and Zonder, J. and Kaufman, J.L. and Bensinger, W. and Dimopoulos, M. and Lendvai, N. and Hari, P. and Ocio, E.M. and Gasparetto, C. and Kumar, S. and Oprea, C. and Chiron, M. and Brillac, C. and Charpentier, E. and San-Miguel, J. and Martin, T.",
    journal = "Leukemia Research",
    year = "2020",
    volume = "34",
    number = "12",
    pages = "3298-3309",
    publisher = "Springer Nature BV",
    issn = "0145-2126",
    doi = "10.1038/s41375-020-0857-2",
    keywords = "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",
    abstract = "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)."
}