In the phase III OPTIMISMM trial, reported by Paul G. Richardson, MD, and colleagues in The Lancet Oncology, researchers found that the addition of pomalidomide to bortezomib/dexamethasone improved progression-free survival in relapsed or refractory multiple myeloma previously treated with lenalidomide.
Paul G. Richardson, MD
The open-label trial included 559 patients from 133 sites in 21 countries who had received one to three previous treatment regimens, including a lenalidomide-containing regimen, for at least two consecutive cycles. Patients were randomly assigned between January 2013 and May 2017 to receive pomalidomide, bortezomib, and dexamethasone (n = 281) or bortezomib and dexamethasone (n = 278).
Pomalidomide was given at 4 mg orally on days 1 to 14 in 21-day cycles. Bortezomib (1.3 mg/m2) was given intravenously or subcutaneously on days 1, 4, 8, and 11 for the first eight cycles and subsequently on days 1 and 8. Dexamethasone (20 mg; 10 mg if age > 75 years) was given on the same days as bortezomib and the day after.
The primary endpoint was progression-free survival in the intention-to-treat population, as assessed by independent review committee.
Progression-Free Survival and Adverse Events
The median follow-up was 15.9 months. Median progression-free survival was 11.20 months in the pomalidomide group vs 7.10 months in the control group (hazard ratio = 0.61, P < .0001). Among 391 patients refractory to lenalidomide in the last lenalidomide-containing regimen, the hazard ratio favoring the pomalidomide group was 0.65 (95% confidence interval = 0.50-0.84).
The most common grade 3 or 4 adverse events in the pomalidomide group were neutropenia (42% vs 9% in the control group; febrile neutropenia in 3% vs 0%), infections (31% vs 18%), and thrombocytopenia (27% vs 29%). Serious adverse events occurred in 57% vs 42% of patients. Treatment-related death occurred in six patients in the pomalidomide group (due to pneumonia in two, unknown cause in two, cardiac arrest in one, and cardiorespiratory arrest in one) and in two patients in the control group (pneumonia in one patient and hepatic encephalopathy in another).
The investigators concluded, “Patients with relapsed or refractory multiple myeloma who previously received lenalidomide had significantly improved progression-free survival when treated with pomalidomide, bortezomib, and dexamethasone compared with bortezomib and dexamethasone. Adverse events accorded with the individual profiles of pomalidomide, bortezomib, and dexamethasone. This study supports use of pomalidomide, bortezomib, and dexamethasone as a treatment option in patients with relapsed or refractory multiple myeloma who previously received lenalidomide.