The optimal dosing of pomalidomide in the treatment of multiple myeloma has not been established. Yale University investigators compared continuous and intermittent dosing regimens, and while the intermittent schedule was associated with more toxicity, they concluded that it is preferable, said Kartik Sehgal, MD, a postdoctoral fellow at Yale University School of Medicine, who reported the study at the 2013 American Society of Hematology Annual Meeting.
“Both continuous and intermittent dosing regimens of pomalidomide with dexamethasone have remarkable clinical activity in heavily pretreated, relapsed/refractory multiple myeloma patients,” Sehgal said. “Our objective was to determine the optimal dosing strategy for patients who relapse after treatment with standard regimens. These 2 dosing regimens have been evaluated in clinical trials but not compared head to head.”
The investigators found that while the intermittent regimen was associated with more grade 3/4 adverse events (AEs)—probably due to a higher dose of pomalidomide—it led to greater maximal reduction in tumor associated immunoglobulin. The intermittent schedule, therefore, is being used in his clinic, Sehgal said.
Details of the Comparison
The single-center randomized phase 2 trial involved 39 patients with myeloma, all of whom were resistant to lenalidomide; approximately 80% were also resistant to bortezomib, and 80% were resistant to both agents. About two-thirds of the group had abnormal molecular cytogenetic profiles.
The continuous dosing group received pomalidomide 2 mg/d on days 1 to 28 of a 28-day cycle, while the intermittent group received pomalidomide 4 mg/d on days 1 to 21 of a 28-day cycle. All patients received dexamethasone 40 mg/wk on days 1, 8, 15, and 22, beginning with cycle 2, until disease progression.
“The question is whether we should give a higher or lower dose of pomalidomide, but at the same time we want to decrease adverse events, so we give a higher dose but with 1 week off, which lessens side effects,” Sehgal said.
Table
Outcomes With the 2 Regimens
The intermittent/higher-dose arm had numerically higher response rates, but the difference was not statistically significant. What was significant, however, was the difference in maximum reduction in disease, Sehgal reported (Table).
Median progression-free survival was similar, 4.4 months with continuous dosing and 5.1 months with intermittent dosing (P = .56). Median overall survival was the same, 17.7 months, in each arm.
“Despite a greater decrease in maximum reduction of disease with the intermittent dose, we did not see a difference in progression-free or overall survival,” he noted.
He said pomalidomide was “pretty well tolerated” but there was a significant increase in pomalidomide-related grade 3/4 AEs with the higher, intermittent dose. Serious drug-related AEs were observed in 8 patients (40%) in the intermittent arm versus 5 patients (26%) in the continuous arm (P = .5), and drug-related grade 3/4 AEs were observed in 18 patients (90%) in the intermittent arm versus 10 patients (53%) with continuous dosing (P = .013).
“We recommend going with the higher, intermittent dosing,” Sehgal told The Oncology Nurse-APN/PA. “This leads to a greater reduction in disease, and this probably gives the patient a better chance for a good outcome. Although there is the possibility of more grade 3 and 4 toxicity, in our experience the side effects are manageable.”
Reference Sehgal K, Kocoglu MH, Deng Y, et al. Comparison of intermittent and continuous dosing regimens of pomalidomide in relapsed/refractory myeloma: results of a phase II randomized trial. Poster presented at: 2013 American Society of Hematology Annual Meeting; December 8, 2013; New Orleans, LA. Abstract 3205.
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