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

Despite advances in combination immuno-chemotherapy and hematopoietic cell transplant (HCT) and improvements in long-term disease-free survival and cure rates for patients with diffuse large B-cell lymphoma (DLBCL) and other B-cell aggressive non-Hodgkin lymphomas (NHL), nearly half of patients will fail therapy and require disease palliation. Vincristine sulfate liposome injection (VSLI; Marqibo^®) was developed to optimize vincristine (VCR) pharmacokinetics, dose-intensification, and target-tissue delivery. VSLI is active in relapsed and refractory NHL as a single-agent and in untreated aggressive NHL as replacement for non-liposomal VCR in CHOP±R combination chemotherapy. Because of a primarily non-hematologic toxicity profile, VSLI may be useful in patients considered unable to tolerate myelosuppressive therapies.

Twenty-two patients with heavily pre-treated, relapsed and refractory CD20+ DLBCL or mantle cell lymphoma (MCL) were treated with combination therapy consisting of VSLI 2.0 mg/m², without a dose cap, every 2 weeks plus 4 weekly doses of rituximab 375 mg/m². Objective response rate (ORR), consisting of achievement of complete response (CR) or partial response (PR), was the primary efficacy endpoint. Secondary efficacy endpoints included response duration, time to progression (TTP), and overall survival (OS). Safety variables included adverse events and neurologic assessments.

The ORR was 59% (13/22) including CR in 6 (27%) patients and PR in 7 (32%) patients. Stable disease was documented in an additional 3 (14%) patients. Median response duration, TTP and OS were 147 days, 121 days and 322 days, respectively. 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. There were no toxicity-associated deaths during the study period. Treatment-related Grade 3 peripheral neuropathy and constipation were reported in 4 patients and 1 patient, respectively. There was no Grade 4 neuropathy. Grade 3 febrile neutropenia developed in 2 patients.

High dose VSLI plus rituximab, as palliative therapy for heavily pre-treated, predominantly older, patients with advanced, relapsed and refractory DLBCL and MCL, was generally well-tolerated and resulted in a meaningful ORR of 59%, median response duration of approximately 5 months, and median OS of almost 11 months. The toxicity profile of this combination was predictable and manageable with limited hematologic toxicity. Despite near universal prior VCR exposure (96%) and doses of VSLI normally unachievable with non-liposomal VCR, peripheral neuropathy and constipation incidences were modest. Older patients, those who are multiply relapsed, and others who are unlikely to tolerate prolonged periods of myelosuppression are often considered best suited for palliative therapy intended to prolong and maintain quality life. VSLI combined with rituximab may provide such palliation.

Off Label Use: Marqibo is currently approved for the treatment of adults with Ph- relapsed/refractory ALL. Deitcher:Talon Therapeutics: Employment, Equity Ownership. Silverman:Talon Therapeutics: Employment.