Isatuximab, a potential therapeutic antibody, can improve survival in relapsed/refractory multiple myeloma patients being given a standard treatment consisting of Pomalyst (pomalidomide) and dexamethasone (brand names include Decadron and Dexpak), results of a pivotal Phase 3 clinical trial suggest.
The data were presented at the 2019 annual meeting of the American Society of Clinical Oncology in Chigaco in a presentation titled, “A phase III randomized, open label, multicenter study comparing isatuximab, pomalidomide, and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.”
Being developed by Sanofi, isatuximab is a monoclonal antibody that targets a protein called CD38. This protein is expressed on most multiple myeloma cells; by targeting it, the therapy can induce cell death via several different mechanisms, including inducing apoptosis (programmed cell death) and targeting the cancer cells for destruction by the body’s immune system.
In the Phase 3 study (NCT02990338), 307 patients with relapsed/refractory multiple myeloma (RRMM) were enrolled at 96 centers in 24 countries. They had received, on average, three previous cycles of therapy, including at least two cycles with Revlimid (lenalidomide) and a proteasome inhibitor, given alone or in combination, but their disease continued to progress (reason for the “relapsed/refractory” part of RRMM).
Patients were randomly assigned to either a standard treatment with pomalidomide and dexamethasone (a control group), or this standard combo plus isatuximab, which was given by injection (at a dose of 10 milligrams per killogram of body weight) weekly for the first four weeks, then every two weeks. Progression-free survival — no evidence of disease returning or progressing, and no patient deaths — at about 18 months was its primary goal.
With an average follow-up time of just under a year (11.6 months), the average progression-free survival time of patients who were treated with isatuximab was 11.53 months, whereas it was 6.47 months in the group that received only pomalidomide and dexamethasone.
Overall response rate in the isatuximab combination group was also significantly greater (60%) than in the control group (35%).
The overall survival rate could not be calculated with confidence due to the short follow-up time, but the researchers also noted a trend towards improvement in the isatuximab group.
This treatment benefit was consistent across multiple sub-group analyses; for example, it remained when the researchers looked only at patients who were older than 75 (the average age of the study population was 67 years old).
“Isatuximab in combination with pomalidomide and dexamethasone resulted in an impressive 40% reduction in the risk of progression or death compared to pomalidomide and dexamethasone alone,” Paul Richardson, MD, a principal investigator in the trial and professor at Harvard Medical School, said in a press release. “This outcome is noteworthy because this trial included a particularly difficult-to-treat, relapsed and refractory patient population that was, in my view, highly reflective of real-world practice.”
Serious (grade 3 or higher) adverse events were reported in 86.8% of the isatuximab group and in 70.5% of the control group, with 7.2% and 12.8% of patients in each respective group discontinuing due to such events. Additionally, 7.9% and 9.4% of patients in each group, respectively, died due to serious adverse events.
Some of the common side effects reported were infections, reactions at the injection site, and neutropenia (decreased numbers of neutrophils, a type of immune cell).