KEY TAKEAWAYS
- The phase 3 trial ICARIA-MM (NCT02990338) study aimed to compare progression-free survival between isatuximab, pomalidomide, and dexamethasone with pomalidomide alone in relapsed and refractory multiple myeloma patients.
- The trial included adults with relapsed and refractory multiple myeloma who had received at least two lines of therapy, including lenalidomide and a proteasome inhibitor.
- Infusion responses, upper respiratory tract infections, and diarrhea were the most prevalent isatuximab-pomalidomide-dexamethasone treatment-emergent side events.
- The study concluded that patients with relapsed and refractory multiple myeloma had better progression-free survival with isatuximab, pomalidomide, and dexamethasone than with pomalidomide alone.
Isatuximab is a monoclonal antibody that targets a particular epitope on the human CD38 receptor and possesses antitumor activity via multiple mechanisms of action. In a previous phase 1b study, approximately 65% of patients with relapsed and refractory multiple myeloma who received the combination of isatuximab, pomalidomide, and low-dose dexamethasone had an overall response. This study compared the progression-free survival (PFS) benefit of isatuximab plus pomalidomide and dexamethasone to pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma.
Researchers conducted a randomized, multicenter, open-label, phase 3 study at 102 institutions in 24 European, North American, and Asia-Pacific countries. Adults with relapsed and refractory multiple myeloma who had received at least two prior lines of therapy, including lenalidomide and a proteasome inhibitor, were eligible to participate. Patients resistant to initial treatment with an anti-CD38 monoclonal antibody were excluded. Patients were randomized (1:1) to receive either isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged 75 years) or pomalidomide 4 mg plus dexamethasone 40 mg. Using interactive response technology, randomization was conducted and stratified according to the number of prior lines of treatment (2-3 vs >3) and age (<75 years vs ≥75 years). The treatments were assigned using a four-block permuted blocked randomization scheme. Isatuximab was administered intravenously to the isatuximab-pomalidomide-dexamethasone group on days 1, 8, 15, and 22 of the first 28-day cycle and days 1 and 15 of subsequent cycles. Both groups were administered oral pomalidomide on days 1 through 21 of each process and oral or intravenous dexamethasone on days 1, 8, 15, and 22 of each cycle. Continue treatment until disease progression, unacceptable toxicity, or withdrawal of consent. For pomalidomide and dexamethasone, dose reductions for adverse reactions were permitted, but not for isatuximab. The primary endpoint was progression-free survival, determined by an independent response committee and measured in the population intended to be treated. All participants who received at least one dose of the study drug were evaluated for safety. Researchers randomly assigned 307 patients to treatment between January 10, 2017, and February 2, 2018: 154 to isatuximab-pomalidomide-dexamethasone and 153 to pomalidomide-dexamethasone. At a median follow-up of 11·6 months (IQR 10·1-13·9), median progression-free survival was 11·5 months (95% CI 8·9-13·9) in the isatuximab-pomalidomide-dexamethasone group versus 6·5 months (4·5-8·3) in the pomalidomide-dexamethasone group; hazard ratio 0·596, 95% CI 0·44-0·81; P=0·001 by stratified log-rank test. The most common treatment-emergent adverse events were infusion reactions (56 [38%] vs 0), upper respiratory tract infections (43 [28%] vs 26 [17%]), and diarrhea (39 [26%] vs 29 [20%]). 12 patients (8%) in the isatuximab-pomalidomide-dexamethasone group and 14 patients (9%) in the pomalidomide-dexamethasone group reported fatal adverse events. One patient (1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection) died due to treatment-related adverse events. The study included that patients with relapsed and refractory multiple myeloma had better PFS with isatuximab, pomalidomide, and dexamethasone than with pomalidomide alone.
Source:https://pubmed.ncbi.nlm.nih.gov/31735560/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02990338
Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Macé S, Corzo KP, Campana F, Le-Guennec S, Dubin F, Anderson KC; ICARIA-MM study group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107. doi: 10.1016/S0140-6736(19)32556-5. Epub 2019 Nov 14. Erratum in: Lancet. 2019 Dec 7;394(10214):2072. PMID: 31735560.
