SAN FRANCISCO—Pomalidomide, bortezomib, and dexamethasone is a highly effective combination in patients with multiple myeloma refractory to lenalidomide, with confirmed responses in 85% of patients (Abstract 304), investigators reported at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.
“Weekly administration of bortezomib enhanced the tolerability and convenience of this regimen,” said Martha Q. Lacy, MD, of the Division of Hematology, Department of Internal Medicine, Mayo Clinic in Rochester, MN.
The phase 1/2 trial enrolled 50 patients with relapsed multiple myeloma who had 1 to 4 prior lines of therapy and were resistant or refractory to lenalidomide. In phase 1, dose level 1 consisted of oral pomalidomide 4 mg days 1 to 21, intravenous or subcutaneously administered bortezomib 1.0 mg/m2 on days 1, 8, 15, and 22, oral dexamethasone 40 mg on days 1, 8, 15, and 22 every 28 days. In phase 2, bortezomib was increased to 1.3 mg/m2 for dose level 2.
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In the 47 patients—6 treated at phase 1 dose level 2 and 41 in the phase 2 portion of the study—evaluable for response, median age was 66 years, 51% were female, and median time from diagnosis of multiple myeloma was 49 months (range 15-142).
The median number of prior regimens was 2. All patients had received lenalidomide; 68%, autologous stem cell transplant; 18%, thalidomide; 53%, alkylating agents; and 57%, bortezomib. Cytogenetics were normal in 60% of patients, abnormal in 36%, and not available in 4%.
Among the 47 patients who were evaluable, confirmed responses (complete response [CR], very good partial response [VGPR], or partial response [PR]) were observed in 40 patients (85%), including stringent CR in 3 patients, CR in 6, VGPR in 12, and PR in 19. Confirmed responses were observed in 9 of the 11 (82%) high-risk patients and median duration of response was 13.7 months (95% confidence interval [CI] 8.5-16.8).
Median progression-free survival was 10.7 months (95% CI 9.4-18.5). Median overall survival was not available. At 6 months, the percentage of event free patients was 100% and, at 12 months it was 94%.
Response rates were 84% in the 19 patients who were high-/intermediate-risk compared with 86% in the 28 patients who were standard risk. Progression-free survival was a median of 9.5 months in the high-/intermediate-risk patients and 16.3 months in the standard-risk patients.
Twenty patients (43%) were currently receiving treatment and 27 had discontinued therapy, 25 for disease progression and 2 for other reasons (physician discretion, stem cell transplant).
The most common hematologic adverse events (AEs), any grade, were anemia, thrombocytopenia, and neutropenia. The most common nonhematologic AEs included fatigue (70%), peripheral neuropathy (64%), and diarrhea (45%).
This combination “is a highly attractive option in patients with relapsed and refractory multiple myeloma,” Dr. Lacy concluded.
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