FDA Updates Pomalidomide Multiple Myeloma Label

Jacqualyn A. Fouse, PhD

The FDA has updated the label for pomalidomide (Pomalyst) plus low-dose dexamethasone to include data from the phase III MM-003 study, which detailed a significant prolongation in progression-free and overall survival for combination versus high-dose dexamethasone alone in patients with relapsed/refractory multiple myeloma.

In the study, patients had received prior treatment with at least two regimens, including lenalidomide and bortezomib. At the final analysis of the MM-003 study, the median progression-free survival (PFS) was 3.6 months with pomalidomide versus 1.8 months with high-dose dexamethasone (HR = 0.45; 95% CI, 0.35-0.59; P <.001). The median overall survival (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).

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.

"There remains a significant unmet need for relapsed/refractory multiple myeloma patients. Pomalyst has been able to help thousands of patients since its approval in 2013 and this data now confirms its survival benefits," Jacqualyn A. Fouse, PhD, president, Global Hematology and Oncology for Celgene, the company marketing the drug, said in a statement. "This label update provides important information about a key product in our industry-leading portfolio of therapies for patients with multiple myeloma."

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.

Pomalidomide, a second-generation immunomodulation agent derived from thalidomide, has a Boxed Warning regarding embryo-fetal toxicity and venous thromboembolism. Additionally, to address the embryo-fetal risk, pomalidomide can only be administered following certification in the Pomalyst Risk Evaluation and Mitigation Strategy (REMS) Program.

At the 2014 ASH Annual Meeting, phase IIIb findings from the single-arm MM-010 study demonstrated intriguing findings for pomalidomide plus low-dose dexamethasone in 599 patients with relapsed and refractory multiple myeloma. At a median follow-up of 6.8 months, the median PFS and OS were 4.2 months and 11.9 months, respectively. The ORR was 35%, with similar findings demonstrated in patients refractory to lenalidomide (n = 572; ORR = 34%) and lenalidomide and bortezomib (n = 473; ORR = 35%).

The drug continues to be explored in a number of clinical trials, including the randomized phase III MM-007 study, also known as OPTIMISMM. In this analysis, the combination of pomalidomide, bortezomib, and low-dose dexamethasone is being compared with bortezomib and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma. The study plans to enroll 782 individuals (NCT01734928).