Τίτλος:
A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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).
Συγγραφείς:
Mikhael, J.
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, J.
Martin, T.
Περιοδικό:
Leukemia Research
Εκδότης:
Springer Nature BV
Λέξεις-κλειδιά:
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
DOI:
10.1038/s41375-020-0857-2
