Convention Center, site of
the 53rd ASH Annual Meeting
Photo courtesy of ASH
SAN DIEGO—Impressive results have been achieved with pomalidomide and low-dose dexamethasone (loDex) in relapsed and refractory patients with multiple myeloma (MM), according to study investigators.
The combination achieved a 34% response rate, including a complete response of 1% and very good partial response of 10% in this population of MM patients refractory to lenalidomide, bortezomib, or both.
Paul Richardson, MD, of Dana-Farber Cancer Institute, reported the results of the phase 1/2 study, known as MM-002, at the 53rd ASH Annual Meeting (abstract 634).
The phase 1 portion of the trial had been reported previously. It established a maximum-tolerated dose of 4 mg daily of pomalidomide.
Dr Richardson called pomalidomide “arguably the most potent of all the IMiDs.” It has significant antimyeloma activity in vitro, promising activity as a single agent in patients with relapsed/refractory MM and efficacy when combined with loDex in patients previously treated with lenalidomide and/or bortezomib.
Dr Richardson pointed out that the investigators defined relapsed and refractory disease rigorously.
“Patients had to have progressed during or 60 days from last treatment, and this had to be confirmed with source documentation prior to study entry,” he said.
In addition, patients had to have measurable levels of M-paraprotein in serum or urine. They must have had 2 or more prior therapies that included 2 or more cycles of lenalidomide and 2 or more cycles of bortezomib, either separately or in combination.
Two hundred twenty-one patients were randomized, 108 to pomalidomide alone and 113 to pomalidomide plus loDex. The pomalidomide regimen was 4 mg daily for 3 weeks with 1 week off. The loDex consisted of 40 mg per week.
Patients were a median age of 63 years. Seventy-eight percent were refractory to lenalidomide, 71% to bortezomib, and 60% to both agents. They had a median of 5 prior therapies, range 2-13.
One hundred ninety-one patients were evaluable for response. They had a median number of 5 cycles of therapy (range, 1-17) and a median duration of 5 months of treatment.
The combination arm had a 34% overall response rate, including partial response or better, compared to 13% in the pomalidomide-alone arm.
Forty-five percent in the combination arm achieved a minor response, compared to 29% in the pomalidomide-alone arm.
And 81% of the patients overall achieved stable disease or better. Responses were rapid and appeared durable, Dr Richardson said.
“What was particularly reassuring and encouraging as well,” he said, “is to see a very similar rate of response for those patients who were refractory to lenalidomide and bortezomib together.” The overall response rate in those patients was 30%.
The median progression-free survival for patients on the combination was 4.7 months. For those on pomalidomide alone, it was 2.7 months.
And the median overall survival on the combination arm was 16.9 months. For those on pomalidomide alone, it was 14 months.
Patients who were refractory to both lenalidomide and bortezomib achieved progression-free survival approaching 4 months with the drug combination and 2 months for pomalidomide alone.
Neutropenia was the dominant grade 3-4 hematologic side effect, followed by thrombocytopenia and anemia. Dose reduction was required in a minority of patients.
The nonhematologic side effects were quite uncommon and included pneumonia and fatigue. No grade 3-4 peripheral neuropathy was reported.
The rate of thromboembolism was less than 5% in either arm. Anticoagulation with low-dose aspirin was required, however.
The investigators concluded that pomalidomide and loDex are synergistic in terms of response rate, and they were impressed that the consistent and durable responses occurred regardless of prior therapy or refractoriness.
On this basis, pomalidomide plus loDex is being investigated in phase 3 trials and as part of combination treatments, including bortezomib.
