According to results from a randomized phase 3 trial presented at the American Society of Clinical Oncology’s recent annual meeting, the addition of isatuximab to pomalidomide and low-dose dexamethasone significantly improvement progression-free survival (PFS) and the overall response rate (ORR) in patients with relapsed or refractory multiple myeloma (RRMM).
According to results from a randomized phase 3 trial presented at the American Society of Clinical Oncology’s annual meeting held in Chicago, Illinois on May 31-June 4, 2019, the addition of isatuximab to pomalidomide and low-dose dexamethasone significantly improvement progression-free survival (PFS) and the overall response rate (ORR) in patients with relapsed or refractory multiple myeloma (RRMM).
Isatuximab, an anti-CD38 monoclonal antibody that contains multiple mechanisms of action for killing tumor cells, including direct tumor targeting and immune cell engagement, “has become a breakthrough target in multiple myeloma therapy and is an important new option for patients with [relapsed or refractory multiple myeloma],” said Paul Richardson, MD, of the Dana-Farber Cancer Institute, during his presentation.
A previous phase 1b study found that isatuximab combined with pomalidomide and dexamethasone is safe and effective in the treatment of RRMM. Based on this finding, investigators launched the phase 3 study, the first trial to examine the addition of an anti-CD38 antibody to pomalidomide plus dexamethasone.
The study enrolled 307 patients with RRMM who had received at least 2 prior lines of therapy with lenalidomide and a proteasome inhibitor. The patients were then randomized to receive isatuximab plus pomalidomide—dexamethasone or pomalidomide monotherapy.
Researchers found that at a median follow up of 11.6 months, the median PFS was significantly longer in the isatuximab plus pomalidomide—dexamethasone arm compared with the pomalidomide arm (11.5 compared with 6.5 months; hazard ratio 0.59, 95% CI [0.44, 0.81]; P < 0.0001). Though median overall survival was not reached in either arm of the trial, a clinically meaningful trend toward improvement was seen with the combination therapy (72% versus 63%).
“These patients represented a true real-world analysis. We included a broad age range, a median time since initial diagnosis that was about 4 years, and, importantly, a number of older patients, patients with chronic obstructive pulmonary disease, and also patients with renal dysfunction and those at high cytogenic risk,” said Richardson.
The combination treatment was generally manageable, reported Richardson, though the addition of isatuximab to pomalidomide did increase rates of grade 3 or higher treatment-emergent adverse events (86.8% in isatuximab plus pomalidomide versus 70.5% in pomalidomide).
Additionally, Richardson explained that “The [quality of life] was maintained with the 3 drugs, versus the 2, with remarkable consistency.”