In patients with multiple myeloma refractory to lenalidomide, pomalidomide administered in a lower-dose, continuous schedule resulted in overall and event-free survival similar to that of intermittent dosing, which is approved by the Food and Drug Administration, according to a report published in Blood.
Both regimens led to rapid activation of innate and adaptive immunity and benefitted expected survival in the heavily pretreated patient population. The cohort given intermittent dosing had a mean 54% reduction in measurable disease, compared with 28% for the cohort given continuous dosing (P = .02); both cohorts had similar event-free survival (4.3 vs. 5.3 months) and overall survival (21.7 vs. 17.7 months).
“In our study, although the 21/28-day schedule led to a greater reduction in measurable disease (although the differences in overall response rate did not reach statistical significance), it also led to a greater incidence of grade 3/4 treatment-related adverse events. Taken together, in our view, these data do not suggest a clear advantage for either regimen based on clinical parameters alone,” wrote Dr. Kartik Sehgal of Yale University, New Haven, Conn., and his colleagues (Blood 2015 June 25 [doi:10.1001/jamaoncol.2015.2010]).
The prospective phase II trial randomized 39 patients, who had received at least two (median four) prior therapies including lenalidomide, to receive pomalidomide in continuous (2 mg/day for 28/28 days) or intermittent (4 mg/day for 21/28 days) dosing schedules. All patients received dexamethasone at 40 mg weekly, starting with cycle two.
The most common adverse effect was myelosuppression, and the pattern of specific toxicities was similar in the two groups. Patients in the intermittent dosing cohort experienced more grade 3/4 adverse effects than the continuous dosing cohort (90% vs. 58%; P = .03).
Both pomalidomide and lenalidomide share the same cellular target (cereblon), and pharmacodynamic studies of the two pomalidomide regimens sought to clarify the mechanism of pomalidomide activity in lenalidomide-refractory multiple myeloma. The data suggest that pomalidomide affects the tumor microenvironment and immune cells. These effects may be amplified by blockade of immune checkpoints, the authors noted.
“Optimizing the immune effects of pomalidomide/lenalidomide on the tumor microenvironment with combination therapies may enhance their therapeutic potential in MM [multiple myeloma] and other cancers,” the authors wrote.