Adding low-dose cyclophosphamide to lenalidomide and prednisone is an active oral combination regimen among patients with multiple myeloma refractory to lenalidomide, according to a study published in Blood.1

The prognosis of patients who are refractory to lenalidomide and bortezomib is very poor; new treatment strategies are needed to improve outcomes for this population. Various studies demonstrate improved response rates and prolonged progression-free survival among patients treated with novel agents such as carfilzomib, ixazomib, elotuzumab, and daratumumab, as part of triplet regimens with lenalidomide and dexamethasone. Patients with lenalidomide-refractory disease were not, however, eligible to participate.

Researchers evaluated the activity and safety of cyclophosphamide, lenalidomide, and prednisone among patients with advanced multiple myeloma. For the phase 1/2 REPEAT study (Revlimid, Endoxan, Prednison Evaluation After Prior Revlimid Treatment; ClinicalTrials.gov Identifier: NCT01352338), investigators enrolled a total of 82 patients, all of whom had lenalidomide-refractory disease.

Among the 67 patients treated with maximum tolerated dose, the overall response rate was 67%; 83% achieved at least a minimal response. Median progression-free survival and overall survival were 12.1 months and 29.0 months, respectively.

Similar findings were observed among patients with disease refractory to both lenalidomide and bortezomib, as well as among patients with high-risk cytogenetic abnormalities.

RELATED: MRD-negative Status Linked With Better Survival in Multiple Myeloma

The most common adverse events were hematologic toxicities, including grade 3 to 4 neutropenia in 22% of patients, grade 3 anemia in 4%, and grade 3 to 4 thrombocytopenia in 17%. The most frequently reported non-hematologic toxicity was infection, which included mostly upper and lower respiratory tract infections.

The findings suggest that continuous low-dose cyclophosphamide with lenalidomide and prednisone is a potential multidrug therapeutic strategy for patients with refractory multiple myeloma.

Reference

  1. Nijhof IS, Franssen LE, Levin M-D, et al. Phase 1/2 study of lenalidomide combined with low-dose cyclophosphamide and prednisone in lenalidomide-refractory multiple myeloma. Blood. 2016 Sep 19. doi: 10.1182/blood-2016-07-729236 [Epub ahead of print]