Current evidence supports the use of maintenance lenalidomide therapy following autologous stem-cell transplant (ASCT) in increasing progression-free survival, time to progression, and overall survival; however, the use of proteasome inhibitors (PIs) has been restricted by the need for intravenous/subcutaneous administration. Shah and colleagues reported the results of a single-arm phase 2 study that evaluated the combination of the oral PI ixazomib plus lenalidomide as post-ASCT maintenance therapy in patients with newly diagnosed multiple myeloma (MM).1 Maintenance therapy consisted of 28-day cycles of ixazomib (initially starting dose of 4 mg but later amended to 3 mg; on days 1, 8, 15) plus lenalidomide (10 mg daily on days 1-28; 15 mg daily after 3 months if well-tolerated). This maintenance regimen was initiated 60 to 180 days post-ASCT. A total of 65 patients received a median of 10 cycles; 11 of the patients had unfavorable cytogenetics (t(14,16), t(4;14), CK51B amplification, del 17p, or high lactic dehydrogenase).
In terms of efficacy, the median progression-free survival (PFS) has not been reached, and the estimated 2-year PFS was 83%. Improvements in overall response rates were observed in 22% of the patients. Grade 3/4 hematologic adverse events (AEs) included anemia (n = 2; grade 3), neutropenia (n = 13; grade 3), neutropenia (n = 2; grade 4); and thrombocytopenia (n = 7; grade 3/4). Grade 3/4 treatment-related nonhematologic AEs included elevated aspartate aminotransferase (n = 3; grade 3), back pain (n = 2; grade 3), constipation (n = 4; grade 3), creatinine increase (n = 2; grade 3), nausea and diarrhea (n = 2; grade 3), and fatigue (n = 4; grade 3). Other AEs of interest included rash (grade 1/2, 10 patients; grade 3/4, 8 patients), peripheral neuropathy (grade 1/2, 42 patients; grade 3, 1 patient), infectious complications (n = 17; grade 2 or 3), and respiratory failure (n = 2). Dose reductions of ixazomib were needed in 14 patients, mostly due to peripheral neuropathy (n = 5) and neutropenia (n = 3); lenalidomide dose reductions were needed in 20 patients, mainly due to cytopenias (n = 11) and rash (n = 2). This reported incidence of AEs for the combination of ixazomib plus lenalidomide maintenance therapy is similar to historical experience with lenalidomide alone. Based on these results, it was concluded that long-term administration of lenalidomide/ixazomib as maintenance therapy post-ASCT was feasible and well-tolerated in patients with newly diagnosed MM.
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