Combination Therapy for Patients with Multiple Myeloma

Chicago—An analysis of a phase 3, randomized, multicenter, open-label study found that patients with pretreated relapsed and refractory multiple myeloma had an improvement in health-related quality of life if they received pomalidomide plus low-dose dexamethasone compared with high-dose dexamethasone. The group that took pomalidomide plus low-dose dexamethasone also had a prolonged time to clinically meaningful disease worsening.

Results were presented during a poster session at the ASCO meeting. The poster was titled Quality of Life Improvements for Pomalidomide plus Low-Dose Dexamethasone in Relapsed and Refractory Multiple Myeloma Patients Enrolled in MM-003.

The FDA approved pomalidomide in February 2013 to treat patients with relapsed and refractory multiple myeloma who experienced disease progression after receiving at least 2 previous cancer drugs, including lenalidomide and bortezomib. Pomalidomide, an oral medication, was granted orphan drug status because it is intended to treat a rare disease.

The authors mentioned that there is no cure for multiple myeloma, and the median overall survival for patients with relapsing and refractory disease with no response to bortezomib and lenalidomide or thalidomide is 9 months. If they receive no further treatment, the median overall survival is 3 months. They added that relapsing and remitting disease may be associated with adverse events such as fatigue, pain, and end-organ damage.

In the MM-003 trial, 455 patients were randomized in a 2:1 ratio to receive pomalidomide plus low-dose dexamethasone or high-dose dexamethasone. Patients were included if they were ≥18 years of age and had refractory or relapsed and refractory disease. Exclusion criteria included thrombocytopenia, grade ≥2 peripheral neuropathy, resistance to high-dose dexamethasone, and creatinine clearance <45 mL/min. The primary end point was progression-free survival; secondary end points included overall response rate, duration of response, quality of life, and safety.

In this analysis, the authors assessed health-related quality of life based on 5 clinically meaningful domains measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items. They chose the following domains after discussions with specialists: (1) global health status, (2) physical functioning, (3) emotional functioning, (4) fatigue, and (5) pain.

The baseline demographics in the groups were similar. The median age was 64 years, 59% of patients were males, and 78% were whites. The median number of prior therapies was ≥5, and 94% of patients had received >2 prior therapies.

A cross-sectional analysis found patients taking pomalidomide plus low-dose dexamethasone had a significant improvement in quality of life measures in 4 of the 5 domains compared with the high-dose dexamethasone group: (1) global health status, (2) physical functioning, (3) emotional functioning, and (4) fatigue. Similar results were found in a longitudinal analysis.

In addition, patients in the pomalidomide plus low-dose dexamethasone group had a prolonged median time to first meaningful disease worsening. The median time to first disease worsening was significantly prolonged with the combination treatment with regard to emotional functioning (P=.023) and fatigue (P=.038).

The authors concluded that the results showing clinically meaningful improvements in health-related quality of life could potentially lead to enhancing the lives of patients with relapsed and refractory multiple myeloma. They added that patients must also have adverse events properly managed to extend treatment duration and maximize the efficacy of pomalidomide plus low-dose dexamethasone.

Celgene Corporation provided financial support for this study.