Updated Data for Pomalidomide in Relapsed/Refractory Multiple Myeloma

David Siegel, MD, PhD

In an updated analysis of the phase III MM-003 trial, Celgene International Sarl, the makers of pomalidomide, reported on a new progression-free survival (PFS) analysis and final overall survival (OS) in September 2013.¹At a median follow-up of 10 months, the company reported, oral pomalidomide plus low-dose dexamethasone had continued to demonstrate significantly longer PFS vs the high-dose dexamethasone comparator (4.0 months vs 1.9 months (hazard ratio [HR]=0.48,P<.0001).⁴

In addition, the combination of pomalidomide plus low-dose dexamethasone &ldquo;demonstrated a significant improvement in OS compared with high-dose dexamethasone (12.7 months vs 8.1 months, HR=0.74,P=.0285). The overall response rate for patients receiving oral pomalidomide plus low-dose dexamethasone was significantly higher, at 31%, compared with 10% in patients who received high-dose dexametahsone (P<.0001).¹

The most common grade 3-4 hematologic adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone arms, respectively, were neutropenia (48% vs 16%), anemia (33% vs 37%), and thrombocytopenia (22% vs 26%). Grade 3-4 nonhematologic adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone arms, respectively, included pneumonia (13% vs 8%), bone pain (7% vs 5%), and fatigue (5% vs 6%).¹

Manish Sharma, MD, on the Use of Pomalidomide

Sharma is an assistant professor in the Department of Medical Oncology at the Kimmel Cancer Center at Thomas Jefferson University.

Strongly positive data from MM-003, first reported in December 2012,²has led to the suggestion that pomalidomide plus low-dose dexamethasone should become the &ldquo;&hellip;standard of care for patients with relapsed and refractory multiple myeloma after treatment with lenalidomide and bortezomib.&rdquo; And, in fact, in February 2013, the FDA granted accelerated approval of pomalidomide (Pomalyst) for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and bortezomib, and whose disease progressed within 60 days of completion of the last therapy.^3,4

At the December 2012 American Society of Hematology (ASH) Annual Meeting, investigators reported that the study had met its primary endpoint. At a median follow-up of 4.2 months, patients receiving pomalidomide plus low-dose dexamethasone had a significant improvement in PFS with the combination regimen (3.8 months vs 1.9 months, HR=0.41,P<.0001). The secondary endpoint of OS also favored the combination, at 11.9 months vs 7.8 months (HR=0.53,P<.0002).²

According to David Siegel, MD, PhD, from John Theurer Cancer Center at Hackensack University Medical Center in New Jersey and an investigator for pomalidomide, the drug offers a treatment option for patients who no longer respond to thalidomide and lenalidomide. The pomalidomide combination may change the picture in multiple myeloma, experts believe, including Meletios Dimopoulos, MD, professor and chair, Clinical Therapeutics at Alexandria Hospital in Athens, Greece, who led the MM-003 study.

References

1. Celgene International Sarl. Celgene issues results of phase III study on pomalidomide plus low-dose dexamethasone. Available at: http://newsroom.celgene.com/press-release/product/results-phase-iii-study-mm-003-pomalidomide-plus-low-dose-dexamethasone-versus
2. Dimopoulos MA, Lacy MQ, Moreau P, et al. Pomalidomide in combination with low-dose dexamethasone: Demonstrates a significant progression free survival and overall survival advantage, in relapsed/refractory MM: A phase 3, multicenter, randomized, open-label study.Blood. 2012;120:Abstract 6.
3. National Cancer Institute (NCI). FDA Approval for Pomalidomide. Available at: http://www.cancer.gov/cancertopics/druginfo/fda-pomalidomide
4. Pomalyst (pomalidomide). Full Prescribing Information. Available at: http://www.pomalyst.com/