A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma. Leukemia 2020 Dec;34(12):3298-3309
Date
05/16/2020Pubmed ID
32409691Pubmed Central ID
PMC7685976DOI
10.1038/s41375-020-0857-2Scopus ID
2-s2.0-85084684633 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
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.
Author List
Mikhael J, Richter J, Vij R, Cole C, Zonder J, Kaufman JL, Bensinger W, Dimopoulos M, Lendvai N, Hari P, Ocio EM, Gasparetto C, Kumar S, Oprea C, Chiron M, Brillac C, Charpentier E, San-Miguel J, Martin TAuthor
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ADP-ribosyl Cyclase 1Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
Female
Humans
Male
Middle Aged
Multiple Myeloma
Neoplasm Recurrence, Local
