Vincristine sulfate liposomes injection (Marqibo) in heavily pretreated patients with refractory aggressive non-Hodgkin lymphoma

Report of the Pivotal Phase 2 Study

Authors

  • M. A. Rodriguez MD,

    Corresponding author
    1. Lymphoma/Myeloma Department, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    • Department of Lymphoma/Myeloma, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0429, Houston, Texas 77030
    Search for more papers by this author
  • Robert Pytlik MD,

    1. Department of Clinical Hematology, Faculty Hospital Kralovske Vinohrady, Prague
    Search for more papers by this author
    • M.A. Rodriguez and Jane Winter performed research, analyzed data, and wrote the paper. Robert Pytlik performed research for the paper. Biao Lu analyzed data and wrote the paper. Steven Deitcher analyzed the data.

  • Tomas Kozak PhD,

    1. Department of Clinical Hematology, Faculty Hospital Kralovske Vinohrady, Prague
    Search for more papers by this author
  • Mukesh Chhanabhai MD,

    1. Department of Pathology Laboratory Medicine, British Columbia Cancer Agency, University of British Columbia, Vancouver
    Search for more papers by this author
  • Randy Gascoyne MD,

    1. Department of Pathology Laboratory Medicine, British Columbia Cancer Agency, University of British Columbia, Vancouver
    Search for more papers by this author
  • Biao Lu PhD,

    1. Hana Biosciences, Inc., South San Francisco, California
    Search for more papers by this author
    • M.A. Rodriguez and Jane Winter performed research, analyzed data, and wrote the paper. Robert Pytlik performed research for the paper. Biao Lu analyzed data and wrote the paper. Steven Deitcher analyzed the data.

  • Steven R. Deitcher MD,

    1. Hana Biosciences, Inc., South San Francisco, California
    Search for more papers by this author
    • M.A. Rodriguez and Jane Winter performed research, analyzed data, and wrote the paper. Robert Pytlik performed research for the paper. Biao Lu analyzed data and wrote the paper. Steven Deitcher analyzed the data.

  • Jane N. Winter MD

    1. Division of Hematology-Oncology, Department of Medicine, and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
    Search for more papers by this author
    • M.A. Rodriguez and Jane Winter performed research, analyzed data, and wrote the paper. Robert Pytlik performed research for the paper. Biao Lu analyzed data and wrote the paper. Steven Deitcher analyzed the data.


Abstract

BACKGROUND:

Marqibo, a sphingosomal/cholesterol encapsulation of vincristine sulfate has targeted, increased, and sustained delivery of vincristine to tumor tissues. A phase 2, open-label, single-arm, and multinational study evaluated the efficacy and tolerability of Marqibo as a single agent in patients with multiply relapsed or refractory aggressive non-Hodgkin lymphoma (NHL).

METHODS:

Eligible patients had relapsed or refractory de novo or transformed aggressive NHL and prior treatment with at least 2 multiagent chemotherapy regimens. Marqibo was administered at 2 mg/m2, every 2 weeks, for a maximum of 12 cycles or until toxicity or disease progression.

RESULTS:

One hundred and nineteen patients were enrolled and treated on trial. Ninety-six had histological confirmed de novo (N = 89) or transformed (N = 7) aggressive NHL. Median number of cycles was 4 (median dose/cycle 4 mg). Overall response (CR and complete response unconfirmed and PR) was 25% (95% confidence interval [CI], 17, 35), CR and complete response unconfirmed confirmed by external reviewers was 5%. Median overall survival was 6.6 months (Kaplan-Meier estimate, 95% CI, 4.7, 9.8). Grade 3 of 4 neurotoxicity occurred in 32% of patients. All patients had prior neurotoxic agents, and 85% had baseline residual neuropathy symptoms (grades 1-2) from prior treatment.

CONCLUSIONS:

Marqibo is an active agent in patients with heavily pretreated aggressive NHL, and tolerated at approximately twice the dose intensity of standard vincristine. Its activity supports further investigation as a substitution for vincristine in combination treatment of lymphoid disorders. Cancer 2009. © 2009 American Cancer Society.

Ancillary