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Liposomal vincristine for relapsed or refractory Ph-negative acute lymphoblastic leukemia: a review of literature.

ABSTRACT: Acute lymphoblastic leukemia (ALL) is a heterogeneous group of hematologic malignancies that arise from clonal proliferation of immature lymphoid cells in the bone marrow, peripheral blood and other organs. There are approximately 3000 new adult cases diagnosed every year in the United States with a 5-year overall survival ranging from 22% to 50%. Most adult patients with ALL who achieve a complete response will ultimately relapse and for this subset of patients the only hope of curative therapy is successful re-induction to achieve a complete response followed by allogeneic transplant. Conventional vincristine has been used in all phases of ALL therapy but its efficacy is limited by cumulative toxicity, typically neuropathic in nature. Historically, the dose of conventional vincristine has been capped at 2 mg to avoid severe neurotoxicity. Liposomal vincristine [as vincristine sulfate liposomal injection (VSLI)] constitutes encapsulating vincristine in a sphingomyelin/cholesterol envelope. This process is thought to enhance drug delivery to the target tissues, decrease neurotoxicity by reducing the percentage of free drug in the plasma and therefore results in increased efficacy with acceptable toxicity. Results from recent trials using VSLI in the setting of relapsed/refractory Ph-negative ALL have been encouraging. VSLI as salvage monotherapy has been successful in inducing complete responses in a minority of adults with relapsed/refractory ALL so that they can be bridged to stem-cell transplantation. Rigorous post-approval testing needs to be conducted to clarify its utility in the clinic.

SUBMITTER: Pathak P

PROVIDER: S-EPMC3891290 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Liposomal vincristine for relapsed or refractory Ph-negative acute lymphoblastic leukemia: a review of literature.

Pathak Priyanka P Hess Rosemary R Weiss Mark A MA

Therapeutic advances in hematology 20140201 1

Acute lymphoblastic leukemia (ALL) is a heterogeneous group of hematologic malignancies that arise from clonal proliferation of immature lymphoid cells in the bone marrow, peripheral blood and other organs. There are approximately 3000 new adult cases diagnosed every year in the United States with a 5-year overall survival ranging from 22% to 50%. Most adult patients with ALL who achieve a complete response will ultimately relapse and for this subset of patients the only hope of curative therapy ...[more]

PMID: 24490021

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Project description:Adults with relapsed/refractory B-acute lymphoblastic leukemia (ALL) have a complete remission (CR) rate of 20-45% and median overall survival of 3-9 months, depending on the duration of the first remission and number of lines of salvage therapy. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative option for adult patients with relapsed/refractory ALL, and achievement of CR is a crucial step before alloHSCT. Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct with dual specificity for CD19 and CD3, simultaneously binding CD3-positive cytotoxic T cells and CD19-positive B cells, resulting in T-cell-mediated serial lysis of normal and malignant B cells. It recently gained accelerated approval by the US Food and Drug Administration (FDA) for the treatment of relapsed/refractory Philadelphia chromosome-negative ALL, based on a large phase II trial of 189 adults with relapsed/refractory B-ALL, which showed a CR/CRh (CR with partial hematologic recovery) of 43% after two cycles of treatment. Toxicities include cytokine-release syndrome (CRS) and neurologic events (encephalopathy, aphasia, and seizure). CRS can be alleviated by step-up dosing and dexamethasone, without affecting the cytotoxic effect of blinatumomab. The cause of neurologic toxicity is unclear but is also observed with other T-cell therapies and may relate to variable expression of CD19 within the brain. This review encompasses the preclinical rationale of using the BITE® class of compounds (blinatumomab being the only one that is FDA approved), with clinical data using blinatumomab in the relapsed/refractory setting (pediatrics and adults), the minimal residual disease setting (adults), as well as Philadelphia chromosome-positive ALL. The review also examines the main adverse events: their prevention, recognition, and management; possible mechanisms of resistance; causes of relapse. It also summarizes future trials evaluating the drug earlier in the treatment course to improve activity.

Dataset Information

Liposomal vincristine for relapsed or refractory Ph-negative acute lymphoblastic leukemia: a review of literature.

Publications

Liposomal vincristine for relapsed or refractory Ph-negative acute lymphoblastic leukemia: a review of literature.

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