The combination of bortezomib, lenalidomide, and dexamethasone resulted in a partial response or better in more than 60% of patients with relapsed or refractory multiple myeloma, according to results of a phase II trial.
The combination of the proteasome inhibitor bortezomib and the immunomodulatory drug lenalidomide plus dexamethasone resulted in a partial response or better in more than 60% of patients with relapsed or relapsed and refractory multiple myeloma, according to the phase II results of a study published in Blood.
“Preclinical studies indicate that lenalidomide sensitizes multiple myeloma cells to bortezomib and dexamethasone and that dexamethasone activity is also enhanced by bortezomib,” wrote study author Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, and colleagues. “Combinations of bortezomib and/or lenalidomide plus dexamethasone have shown substantial clinical activity in treatment-naive multiple myeloma and bortezomib immunomodulatory-drug–based triplet regimens have shown improved activity vs bortezomib- or immunomodulatory-drug–dexamethasone doublets in the frontline and relapsed settings.”
Once phase I trials indicated that this combination of drugs was safe and clinically active in patients with relapsed/refractory disease, and established a maximum tolerated dose of 15 mg lenalidomide plus 1 mg/m2 bortezomib, Richardson and colleagues began a prospective, phase II study of the combination.
In the trial, 64 patients with relapsed/refractory disease were assigned to eight 21-day cycles of bortezomib 1 mg/m2, lenalidomide 15 mg per day, and dexamethasone 20 or 40 mg per day for cycles one to four and 10 or 20 mg per day for cycles 5 to 8. Any patient experiencing a response could receive maintenance therapy.
Looking at patient characteristics, 58% had relapsed disease and 42% had refractory disease. Fifty-three percent of patients had prior treatment with bortezomib; 75% with thalidomide; and, 6% with lenalidomide.
After a median follow-up of 44 months, 42 patients died, 40 from progressing disease. Seventy-five percent of patients were alive and progression-free for 6 months or longer. The median progression-free survival was 9.5 months and the median overall survival was 30 months.
Overall, 64% of patients had a partial response or better, with a median duration of response of 8.7 months.
Small post hoc analyses showed no difference in response rate according to patient subtypes, including those with relapsed compared with refractory disease.
The most commonly observed treatment-related adverse events were sensory neuropathy (53%), fatigue (50%), and neutropenia (42%). The common grade 3/4 treatment-related events were neutropenia (30%), thrombocytopenia (22%), and lymphopenia (11%).
“Given the observed effectiveness and tolerability of lenalidomide-bortezomib-dexamethasone, there is potential for further development of this three-drug regimen, including the addition of a fourth agent, as has been investigated with combinations of bortezomib and thalidomide,” the researchers wrote.