Key grade 4 hematologic adverse events were neutropenia (17%) and thrombocytopenia (7%). Grade 3 rash occurred in 10% of patients and grade 3/4 neurologic events in 7%. Despite the use of daily low-dose aspirin, 3% of patients experienced grade 3/4 thromboembolism.
Continuous pomalidomide 2.5 mg/day was identified as the maximum tolerated dose in the phase I portion of the study, and is roughly equivalent to the 4-mg dose given on the 3-week on, 1 week-off schedule, Dr. Palumbo said.
Dr. Antonio Palumbo
Progression-free and overall survival data are immature after a median follow-up of only 4 months, but appear "interesting," he added.
Final Analysis of IFM 2009-02. The French-led Intergroupe Francophone du Myélome (IFM) 2009-02 trial tested the combination of pomalidomide 4 mg/day on days 1-21 or given continuously throughout the 28-day cycle, with dexamethasone 40 mg/week in patients with relapsed multiple myeloma who were resistant or refractory to lenalidomide and bortezomib. The 84 patients had a median of five previous lines of therapy, and three-fourths were refractory to lenalidomide and bortezomib.
Considering the duration of response, treatment duration, and similar safety profile, the 3-week on, 1-week off regimen appears superior to the continuous pomalidomide regimen, said Dr. Xavier Leleu of Hospital Huriez, CHRU, in Lille (France).
The median treatment duration was slightly longer at 7.2 months with the 21-day schedule vs. 5.2 months with continuous pomalidomide. The median number of cycles was 8 and 6, respectively.
A partial response or better was observed in 35% of the 21-day group and in 34% of the 28-day group, including very good partial responses in 1% of both groups and stable disease in 44% and 51%, respectively.
The median duration of response was 10.5 months with the 21-day schedule and 7.2 with the continuous schedule, resulting in more patients on the 21-day schedule being responsive at 1 year or more (47.5% vs. 36%), Dr. Leleu said.
Median progression-free survival (PFS) in the entire study was 5.7 months. This compares favorably with a median of 3.8 months in patients refractory to lenalidomide and bortezomib, and a median of 5.7 months in those refractory to lenalidomide as their last line of therapy, he said.
Notably, median PFS was just 3.8 months in patients with stable disease vs. 11.3 months for responders. "Apparently, it [PFS] is significantly lower in patients with stable disease, but if you have patients who are responders, clearly their outcome is really, really good," Dr. Leleu said.
Subgroup analyses revealed poorer PFS in patients with adverse cytogenetics compared with others (2.8 vs. 9.9 months). PFS was also lower in elderly patients than in those under age 65 (4.0 months vs. 6.8 months), although Dr. Leleu said the numbers were small and it was hard to know whether the elderly received all their medication.
Serious adverse events were reported in 33% of patients in the 3-week on, 1-week off regimen and in 41.5% of those on the continuous regimen.
A study is underway evaluating pomalidomide 2 mg daily, but Dr. Leleu said such a regimen would have to be administered carefully. "There is no room for mistakes, because if you don’t treat them in an optimized way, they can escape treatment very quickly," he said. "So if you can manage 4 mg, it is probably better."
Long-Term Outcomes. Finally, Dr. Joseph R. Mikhael and his colleagues evaluated outcomes 4 years after the first Mayo Clinic cohort of relapsed or refractory myeloma patients was treated with continuous pomalidomide 2 mg/day and weekly dexamethasone 40 mg. The patients also received prophylaxis for deep vein thrombosis (DVT) with aspirin, heparin, or warfarin.
The 60 patients were enrolled from November 2007 to August 2008, and had received one to three prior therapies. Those therapies included stem cell transplantation (65%), bortezomib (33%), thalidomide (47%), lenalidomide (35%), immunomodulatory drugs (60%), and radiation (38%).
In all, 32% were high risk according to mSMART criteria, and 78% had International Staging System 2-3 disease.
A median of 11.5 treatment cycles were administered (range 1-47 cycles). All patients also received DVT prophylaxis with aspirin, heparin, or warfarin.
With a median follow-up of 33.6 months, the overall response was 65% (39/60 patients), including 4 stringent complete responses, 4 complete responses, 15 very good partial responses, and 16 partial responses.
Response was no less in patients with high-risk disease at 74% (14/19 patients), according to Dr. Mikhael, a hematologist at the Mayo Clinic in Scottsdale, Ariz.
The responses were durable, with a median duration of 21.3 months. At the time of the analysis, 12 patients (20%) remained on therapy. "Pomalidomide and dexamethasone provides a long-term benefit with median progression-free survival of 13 months and a 2-year survival rate of 76%," the authors wrote.