Vincristine sulfate liposome injection (VSLI; Marqibo) was developed to optimize vincristine pharmacokinetics, dose-intensification, and target-tissue delivery. Approved in the United States in 2012 for the treatment of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia in second or greater relapse or whose disease has progressed following 2 or more antileukemia therapies, VSLI is also known to be active in relapsed NHL as a single agent and in untreated aggressive NHL as replacement for nonliposomal vincristine in CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like combination regimens. Because of its relatively minimal hematologic toxicity profile, VSLI was hypothesized to be useful in patients who are unable to tolerate myelosuppressive therapies.
In this phase 2 study conducted by Kaplan and colleagues, 22 patients with heavily pretreated, relapsed and refractory CD20+ diffuse large B-cell lymphoma or mantle-cell lymphoma were treated with VSLI (2.0 mg/m2 without a dose cap) every 2 weeks plus 4 weekly doses of rituximab (375 mg/m2). The median number of VSLI doses was 5, the median individual VSLI dose was 3.5 mg, and the maximum cumulative VSLI dose was 43 mg.
Among the 22 patients who were evaluable for response, the overall response rate was 59%; 27% of patients achieved complete response and 32% of patients achieved partial response. In addition, stable disease was documented in 14% of patients. The median response duration, time to progression, and overall survival were 147 days, 121 days, and 322 days, respectively.
There were no toxicity-related deaths during the study period. Treatment-related Grade 3 constipation was reported in 1 patient, and treatment-related grade 3 peripheral neuropathy was reported in 4 patients; there was no grade 4 peripheral neuropathy. Grade 3 febrile neutropenia developed in 2 patients.
As palliative therapy for heavily pretreated, predominantly older patients with advanced, relapsed and refractory diffuse large B-cell lymphoma or mantle-cell lymphoma, high-dose VSLI plus rituximab may be a viable option for patients who are unlikely to tolerate prolonged periods of myelosuppression.
Kaplan LD, Deitcher SR, Silverman JA, Morgan GJ. Vincristine sulfate liposome injection (Marqibo®) and rituximab for patients with relapsed and refractory diffuse large B-cell lymphoma or mantle cell lymphoma in need of palliative therapy. Blood. 2013;122. Abstract 4355.