Early-phase studies of the new immunomodulatory drug pomalidomide drew considerable interest at ASH 2011 and generated enthusiasm from myeloma specialists.
Paul G. Richardson, MD, of Dana-Farber Cancer Institute, Boston, who has led trials of pomalidomide, commented, “Over 40% clinical benefit rate and almost 17 months median survival in heavily pretreated patients is fantastic.”
A phase 2 study compared pomalidomide alone versus pomalidomide plus low-dose dexamethasone in 221 patients with relapsed/refractory disease. Patients had received an average of 5 previous lines of therapy, and most of them had progressed with bortezomib or with lenalidomide therapy.
Pomalidomide plus dexamethasone led to a partial response in 34% of patients compared with 13% of patients responding to pomalidomide alone; another 11% of patients had minor responses to the combination regimen.
Median progression-free survival rates were 4.7 months with the combination and 2.7 months with pomalidomide alone, and median overall survival (OS) rates were 16.9 months and 14 months, respectively.
Similar findings emerged from the French phase 2 IFM 2009-02 study of pomalidomide plus low-dose dexamethasone in 84 patients with disease refractory to both lenalidomide and bortezomib.
Responses with the combination were observed in 34.5% of patients, and stable disease was present in 48% of patients. Median time to progression was 9.1 months, and median OS was 13.4 months, according to Xavier Leleu, MD, PhD, of Hôpital Claude Huriez, CHRU, Lille, France.
Pomalidomide Plus 2 Drugs and Maintenance
Italian investigators combined pomalidomide with 2 other agents, cyclophosphamide and prednisone, followed by maintenance with pomalidomide plus cyclophosphamide in a phase 2 study of 29 relapsed/refractory patients.
After a median of 4 cycles, partial response or better was observed in 81% of the patients with refractory disease and in 55.5% of the patients who relapsed. Very good partial response or better was seen in 27% and 28% of patients, respectively, and complete responses were documented in 9% and 5.5% of patients, respectively, according to Antonio Palumbo, MD, of the University of Torino in Italy, for the Italian Multiple Myeloma Network.
Dr Palumbo also suggested that using a combination with “a good risk-benefit ratio, where there is not much toxicity,” and continuing the 3 drugs as maintenance therapy, “may help explain the higher proportion of responses” in this study.
Pomalidomide was generally well tolerated in all studies. The most common grade 3 or 4 toxicities were neutropenia, anemia, pneumonia, thrombocytopenia, and fatigue. More unusual grade 3 or 4 nonhematologic toxicities include rash and central neurologic toxicity in <10% of patients. Phase 3 trials are currently evaluating pomalidomide in various drug combinations.—CH