ATLANTA — Increasing the dose of pomalidomide (Pomalyst) in combination with dexamethasone along with growth factor support in the treatment of newly-diagnosed refractory/relapsed multiple myeloma produced a high rate of responses, researchers reported here.
In a phase II study, all 16 patients achieved a clinical benefit on a dose of 5 mg pomalidomide daily for 21 days of a 28-day cycle, reported Elisabet Manasanch, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Patients also were given dexamethasone 40 mg weekly, with granulocyte-colony stimulation factor support on days 22-28, she reported in her poster presentation at the annual meeting of the American Society of Hematology.
Median progression-free survival was 19.5 months, and after a median follow-up of 22 months, median overall survival in this group of patients had not been reached, she reported.
“Pomalidomide can be safely administered at a dose of 5 mg if given with growth factor support,” she suggested, “providing an encouraging overall response rate of greater than 60% in this cohort of early relapsed multiple myeloma patients.”
Manasanch and colleagues aimed to increase the maximum tolerated dose of pomalidomide — established at 4 mg in multiple myeloma — and by doing that, increase the response rate associated with the treatment. They hypothesized that by adding hematopoietic factors to the treatment regimen they could protect patients against development of neutropenia — a dose-limiting toxicity that has often been observed with pomalidomide.
The trial protocol would have permitted the researchers to increase the pomalidomide dose to 10 mg, but at a dose of 6 mg in the dose-ranging phase I part of the study, dose limiting neutropenia occurred — establishing 5 mg as the highest dose that could be safely administered with growth factors, Manasanch reported. Of the six patients who received 6 mg of pomalidomide, two experienced dose-limiting toxicity, and the treatment was not escalated.
When that dose plus dexamethasone was set as dosing for the phase II level of the trial, the researchers reported the treatment was well tolerated. Grade 3 related hematologic adverse events were two cases of thrombocytopenia; one case of Grade 3 neutropenia and one case of Grade 3 febrile neutropenia. Non-hematologic adverse events was a case of upper respiratory infection and one case of dyspnea. No Grade 4 or Grade 5 adverse events occurred in the trial, the researchers reported.
To be eligible for the study, patients had to have been diagnosed with refractory/relapsed multiple myeloma, had adequate bone marrow reserve and had measurable disease. Their previous treatment had to have included at least two cycles of lenalidomide (Revlimid) and bortezomib (Velcade). While the criteria included patients that had been heavily pre-treated for multiple myeloma, the researchers set 5 previous lines of therapy as the limit for this study. The median number of previous lines of therapy was three.
Historically, 4 mg of pomalidomide resulted in a 30% response rate. Manasanch suggested a phase 3 comparative study was needed to test in a prospective fashion whether 4 mg or 5 mg was the best choice for early treatment of relapsed/refractory multiple myeloma.
Response rates in the study included a 62.5% objective partial response rate and a 37.5% minimal response rate. But noting that “this was a very small study,” Jonathan Kolitz, MD, of Northwell Health Cancer Institute, Lake Success, New York, questioned whether it was clinically significant enough to guide practice.
“And the increase of the dose was really just about 25%,” told MedPage Today. “The improvement in outcomes is difficult to assess considering the small numbers of patients.”
He suggested that the interest in increasing the dose of pomalidomide — considered one of the more potent drugs in the class which includes thalidomide — would not likely be pursued in the current era of multiple myeloma therapies that has branched into use of monoclonal antibodies and gene therapies.
The researchers enrolled 20 patients in the combined phase I/II trial, recruiting them from June 2014 through November 2016. There were 12 patients in the dose-ranging phase I part of the study; eight patients participated in the phase II part of the trial.
Manasanch disclosed relevant relationships with Celgene, Merck, Sanofi, Quest Diagnostics, Takeda and Adaptive Biotechnologies.