A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma Journal Article


Authors: Martin, T.; Baz, R.; Benson, D. M.; Lendvai, N.; Wolf, J.; Munster, P.; Lesokhin, A. M.; Wack, C.; Charpentier, E.; Campana, F.; Vij, R.
Article Title: A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma
Abstract: This phase 1b, open-label, dose-escalation study assessed the safety, efficacy, and pharmacokinetics of anti-CD38 monoclonal antibody isatuximab given in 2 schedules (3, 5, or 10 mg/kg every other week [Q2W] or 10 or 20 mg/kg weekly [QW] for 4 weeks and then Q2W thereafter [QW/Q2W]), in combination with lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (QW), in patients with relapsed/refractory multiple myeloma (RRMM). Patients received 28-day treatment cycles; the primary objective was to determine the maximum tolerated dose (MTD) of isatuximab with lenalidomide and dexamethasone. Fifty-seven patients (median 5 [range 1-12] prior regimens; 83% refractory to previous lenalidomide therapy) were treated. Median duration of dosing was 36.4 weeks; 15 patients remained on treatment at data cutoff. Isatuximab-lenalidomide-dexamethasone was generally well tolerated with only 1 dose-limiting toxicity reported (grade 3 pneumonia at 20 mg/kg QW/ Q2W); the MTD was not reached. The most common isatuximab-related adverse events were infusion-associated reactions (IARs) (56%), which were grade 1/2 in 84% of patients who had an IAR and predominantly occurred during the first infusion. In the efficacy-evaluable population, the overall response rate (ORR) was 56% (29/52) and was similar between the 10 mg/kg Q2W and 10 and 20 mg/kg QW/Q2W cohorts. The ORR was 52% in 42 evaluable lenalidomide-refractory patients. Overall median progression-free survival was 8.5 months. Isatuximab exposure increased in a greater than dose-proportional manner; isatuximab and lenalidomide pharmacokinetic parameters appeared independent. These data suggest that isatuximab combined with lenalidomide and dexamethasone is active and tolerated in heavily pretreated patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT01749969. (Blood. 2017;129(25): 3294-3303) © 2017 by The American Society of Hematology
Keywords: adolescent; cancer survival; treatment response; aged; major clinical study; overall survival; lenalidomide; drug tolerability; fatigue; neutropenia; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; drug withdrawal; hypertension; treatment duration; progression free survival; multiple cycle treatment; multiple myeloma; anemia; leukopenia; nausea; thrombocytopenia; vomiting; cytogenetics; dexamethasone; deep vein thrombosis; coughing; dyspnea; febrile neutropenia; fever; hyperglycemia; lymphocytopenia; pneumonia; lung embolism; hypokalemia; hyponatremia; hypotension; insomnia; maculopapular rash; multicenter study; thromboembolism; sepsis; open study; headache; maximum tolerated dose; phase 1 clinical trial; drug dose increase; lung infection; muscle spasm; anaphylaxis; upper respiratory tract infection; bronchospasm; nose obstruction; face edema; infusion related reaction; operative blood loss; human; male; female; priority journal; article; isatuximab
Journal Title: Blood
Volume: 129
Issue: 25
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2017-06-22
Start Page: 3294
End Page: 3303
Language: English
DOI: 10.1182/blood-2016-09-740787
PROVIDER: scopus
PMCID: PMC5482100
PUBMED: 28483761
DOI/URL:
Notes: Article -- Export Date: 2 August 2017 -- Source: Scopus
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MSK Authors
  1. Nikoletta Lendvai
    78 Lendvai
  2. Alexander Meyer Lesokhin
    106 Lesokhin