Paul Richardson, MD
Adding pomalidomide (Pomalyst) to the combination of bortezomib (Velcade) and low-dose dexamethasone (PVd) led to a significant improvement in progression-free survival (PFS) in patients with relapsed/refractory myeloma with prior exposure to lenalidomide (Revlimid), according to findings from the phase III OPTIMISMM trial.
The positive result was reported by Celgene, the manufacturer of pomalidomide. The company did not report any additional data, but noted that there were no new safety signals and that expanded results would be presented at an upcoming medical meeting.
“The OPTIMISMM results confirm the expanding role of pomalidomide in previously treated multiple myeloma patients,” principal investigator Paul Richardson, MD, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at the Dana Farber Cancer Institute, RJ Corman Professor of Medicine, Harvard Medical School, said in a press release. “We see the PVd combination as an important step in improving care, especially for patients previously treated with lenalidomide in this setting.”
The international, open-label phase III OPTIMISMM study randomized patients with relapsed/refractory multiple myeloma to the triplet of pomalidomide, bortezomib, and low-dose dexamethasone, or bortezomib and low-dose dexamethasone alone. Patients were required to have received a minimum of 1 but not more than 3 prior treatments for myeloma, including a lenalidomide containing regimen for at least 2 consecutive cycles. The primary endpoint was PFS, with secondary endpoints including overall survival (OS), overall response, duration of response, and safety.
The FDA granted an accelerated approval to pomalidomide as a treatment for patients with multiple myeloma following 2 prior therapies, including lenalidomide and bortezomib, in February 2013. This initial approval was based on results from the open-label phase II MM-002 trial. In this analysis, the overall response rate (ORR) was 7.4% with pomalidomide alone and 29.2% in patients treated with pomalidomide plus low-dose dexamethasone.
In April 2015, the FDA updated the label for pomalidomide plus low-dose dexamethasone to include data from the phase III MM-003 study, which detailed a significant prolongation in PFS and OS for the combination versus high-dose dexamethasone alone in patients with relapsed/refractory multiple myeloma.
In the study, patients had received prior treatment with at least 2 regimens, including lenalidomide and bortezomib. At the final analysis of the MM-003 study, the median PFS was 3.6 months with pomalidomide versus 1.8 months with high-dose dexamethasone (hazard ratio [HR], 0.45; 95% CI, 0.35-0.59; P
<.001). The median OS was 12.4 versus 8.0 months, with pomalidomide versus high-dose dexamethasone, respectively (HR, 0.70; 95% CI, 0.54-0.92; P = .009).
In the phase III study, 455 patients with multiple myeloma were randomized to pomalidomide plus low-dose dexamethasone (n = 302) or high-dose dexamethasone alone (n = 153). Patients received pomalidomide at 4 mg daily for 3 weeks in a 28-day cycle. Dexamethasone was administered at 40 mg; in the high-dose arm this consisted of a daily dose on days 1 to 4, 9 to 12, and 17 to 20.
Overall, 95% of patients were refractory to lenalidomide and 79% were refractory to bortezomib, with 75% of patients refractory to both medications. Patients had received a median of 5 prior therapies.
An independent review adjudication committee completed the final analysis for PFS and OS following approximately 50% of events. The ORR at this analysis was 23.5% with pomalidomide versus 3.9% with high-dose dexamethasone. There was 1 complete response with pomalidomide (0.3%) and 8 very good partial responses (2.6%).
The most common all-grade adverse reactions reported with pomalidomide (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper respiratory tract infections, back pain, and pyrexia. The most frequently reported grade 3/4 adverse event was neutropenia (46%). The rate of febrile neutropenia was 8%. Overall, 67% of patients had a dose interruption on pomalidomide and 27% required a dose reduction.