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ASH 2014

Sessions Report Phase 2 Results on Pomalidomide Combinations

Pomalidomide was approved by FDA in February 2013 for multiple myeloma patients whose disease has progressed despite having received at least 2 other therapies. On Monday, researchers at the American Society of Hematology Annual Meeting presented results of phase 2 studies on combinations with the immunomodulatory drug.
Results from a pair of phase 2 studies involving pomalidomide were reported in Monday’s oral abstract sessions on treatments for multiple myeloma, as researchers continue to develop new combinations for patients who have stopped responding to earlier treatments.

Pomalidomide, an immunomodulatory drug marketed as Pomalyst, received FDA approval in February 2013 for multiple myeloma patients whose disease is demonstrating progression despite having had at least 2 other therapies, including lenalidomide and bortezomib.1

Results presented early Monday featured 2 combinations. A phase 1/2 study found pomalidomide with bortezomib and dexamethasone was highly effective with confirmed responses over 80%.2 A second study found pomalidomide with cyclophosphamide and dexamethasone was superior to pomalidomide and dexamethasone only.3

Pomalidomide, bortezomib and dexamethasone. Martha Q. Lacy, MD, of the Mayo Clinic presented results involving 50 patients who had previously been treated with 1-4 therapies (median 3) and were not responding to lenalidomide.2 The median age was 66, and 51% were female. The median time from diagnosis to the time of the study was 46 months, and 68% had received a stem cell transplant.

Dosing was as follows: In phase 1, 9 patients started on received 4 mg of pomalidomide on days 1-21, bortezomib 1 mg/m2 weekly, and 40 mg of dexamethasone weekly. For 6 patients, dosing of bortezomib was increased to 1.3 mg/m2 , and this dose level was adopted for the larger group of patients in phase 2.

At 9 months, 72% of the patients were progression free, 96% were alive and 66% remain on treatment. Common adverse events (AEs) were anemia, fatigue, leukopenia, and thrombocytopenia, with the majority grade 1-2. AEs grade 3 and higher were: neutropenia (29) leukopenia (15), lung infection (6), lymphopenia (8), dyspnea (3) and syncope (3). Pulmonary embolism occurred in 1 patient. Among the 42 patients who could be evaluated, confirmed responses were seen in 34, including 9 of 11 high-risk patients. Median progression-free survival (PFS) was 17.7 months.

Treatment with and without cyclophosphamide. Previously reported results of pomalidomide with dexamethasone had an overall response rate (ORR) of 33% and median PFS of 4.2 months in patients who have previously been treated with bortezomib and lenalidomide. This phase 2 trial involving 70 randomly assigned patients compared one arm of patients receiving the pomalidomide-dexamethasone combination (median age 63) with a second arm also receiving cyclophosphamide (median age 64).3

Dosing of dexamethasone was adjusted by age, and patients not receiving cyclophosphamide were allowed to cross over to join that arm if their disease progressed. After a median follow-up of 15 months, ORR (partial response or better) for the arm receiving pomalidomide and dexamethasone was 39%, while it was 65% for the arm also receiving cyclophosphamide. Clinical benefit (minimal response or better) was 64% to 79%. Median PFS was 4.4 months compared with 9.2 months, respectively. Grade 3/4 AEs were more frequent in patients receiving cyclophosphamide, although the authors reported these were not statistically significant.

While the study ended in March 2014, the authors reported that as of July 2014, 28 of the original 70 patients had died; 16 who did not start out in the arm receiving cyclophosphamide, and 12 who did. During the study 13 patients crossed into the second arm.

References

  1. Shilane J. Pomalyst: Questions and answers about the FDA approval. The Myeloma Beacon. http://www.myelomabeacon.com/news/2013/02/13/pomalyst-pomalidomide-questions-and-answers-fda-approval/. Published February 13, 2013. Accessed December 9, 2014.
  2. Lacy MQ, LaPlant BR, Laumann KM, et al. Pomalidomide, bortezomib, and dexamethasone (PVD) for patients with relapsed lenalidomide refractory multiple myeloma (MM). Blood. 2014; 124 (21): Abstract 304.
  3. Baz R, Martin TG, Alsina M, et al. Pomalidomide, cyclophosphamide, and dexamethasone is superior to pomalidomide and dexamethasone in relapsed and refractory myeloma: results of a multicenter phase 2 study. Blood. 2014; 124 (21): Abstract 303.
 

 
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