New era for myelofibrosis treatment with novel agents beyond Janus kinase-inhibitor monotherapy: Focus on clinical development of BCL-XL /BCL-2 inhibition with navitoclax

Cancer. 2023 Nov 15;129(22):3535-3545. doi: 10.1002/cncr.34986. Epub 2023 Aug 16.

Abstract

Myelofibrosis is a heterogeneous myeloproliferative neoplasm characterized by chronic inflammation, progressive bone marrow failure, and hepatosplenic extramedullary hematopoiesis. Treatments like Janus kinase inhibitor monotherapy (e.g., ruxolitinib) provide significant spleen and symptom relief but demonstrate limited ability to lead to a durable disease modification. There is an urgent unmet medical need for treatments with a novel mechanism of action that can modify the underlying pathophysiology and affect the disease course of myelofibrosis. This review highlights the role of B-cell lymphoma (BCL) protein BCL-extra large (BCL-XL ) in disease pathogenesis and the potential role that navitoclax, a BCL-extra large/BCL-2 inhibitor, may have in myelofibrosis treatment.

Keywords: B-cell lymphoma-extra large (BCL-XL) inhibition; REFINE; disease modification; myelofibrosis (MF); navitoclax.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Humans
  • Janus Kinase 2
  • Janus Kinase Inhibitors* / pharmacology
  • Janus Kinase Inhibitors* / therapeutic use
  • Nitriles / therapeutic use
  • Primary Myelofibrosis* / drug therapy
  • Proto-Oncogene Proteins c-bcl-2

Substances

  • Janus Kinase Inhibitors
  • navitoclax
  • Janus Kinase 2
  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Nitriles