Final results of a phase 1b study of isatuximab short-duration fixed-volume infusion combination therapy for relapsed/refractory multiple myeloma

Saad Z Usmani, Chatchada Karanes, William I Bensinger, Anita D'Souza, Noopur Raje, Sascha A Tuchman, Douglas Sborov, Jacob P Laubach, Giada Bianchi, Dheepak Kanagavel, Rao Saleem, Franck Dubin, Frank Campana, Paul G Richardson, Saad Z Usmani, Chatchada Karanes, William I Bensinger, Anita D'Souza, Noopur Raje, Sascha A Tuchman, Douglas Sborov, Jacob P Laubach, Giada Bianchi, Dheepak Kanagavel, Rao Saleem, Franck Dubin, Frank Campana, Paul G Richardson

Abstract

Part B of this phase 1b study (ClinicalTrials.gov number, NCT02283775) evaluated safety and efficacy of a fixed-volume infusion of isatuximab, an anti-CD38 monoclonal antibody, in combination with pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma patients. Isatuximab (10 mg/kg weekly for 4 weeks, then every other week) was administered as a fixed-volume infusion of 250 mL (mL/h infusion rate) with standard doses of Pd on 28-day cycles. Patients (N = 47) had a median of three prior treatment lines (range, 1-8). Median duration of exposure was 36.9 weeks and median duration of first, second, and 3+ infusions were 3.7, 1.8, and 1.2 h, respectively. The most common non-hematologic treatment-emergent adverse events were fatigue (63.8%), infusion reactions (IRs), cough, and upper respiratory tract infection (40.4% each). IRs were all grade 2 and occurred only during the first infusion. The overall response rate was 53.2% in all patients (55.5% in response-evaluable population, 60.0% in daratumumab-naïve patients). Efficacy and safety findings were consistent with data from the isatuximab plus Pd infusion schedule in Part A of this study and also from the phase 3 ICARIA-MM study, and these new data confirm the safety, efficacy, and feasibility of fixed-volume infusion of isatuximab.

Conflict of interest statement

SZU: Research funding from Amgen, Array, BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, and Takeda; Consulting fees from Amgen, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Sanofi, SkylineDX, and Takeda; Speaking fees from Amgen, Celgene, Janssen, and Takeda. CK: Nothing to disclose. WIB: Grant funding from Amgen, Bristol Myers Squibb, Janssen, and Sanofi; Personal fees from Amgen, Bristol Myers Squibb, Janssen, and Takeda. ADS: Research funding from Merck, Mundipharma EDO, Prothena, Sanofi, Takeda, and TeneoBio; Consulting fees from Akcea, Imbrium, Janssen, and Pfizer. NR: Consulting fees from Bristol Myers Squibb and Celgene. SAT: Research funding from Celgene, Janssen, Karyopharm, and Sanofi; Consulting fees from Alnylam, Caelum, Celgene, Karyopharm, and Oncopeptides; Speaking fees from Celgene. DS: Consulting fees from Celgene and Janssen. JL: Nothing to disclose. GB: Consulting fees from Pfizer. DK, RS, FD, and FC: Employed by Sanofi. PGR: Grant funding from Bristol Myers Squibb, Celgene, Oncopeptides, and Takeda; Personal fees from Celgene, Janssen, Karyopharm, Oncopeptides, Sanofi, and Takeda.

© 2021. The Author(s).

Figures

Fig. 1. Treatment schedule.
Fig. 1. Treatment schedule.
d dexamethasone, IR infusion reaction, Isa isatuximab, IV intravenous, P pomalidomide, PO orally, QW weekly, Q2W every other week.
Fig. 2. Fixed-volume infusion of isatuximab.
Fig. 2. Fixed-volume infusion of isatuximab.
Duration of isatuximab infusion, by infusion number for Part A (weight-based infusion volume; mg/h) and Part B (fixed-volume infusion; mL/h).

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