SOHO State of the Art Updates and Next Questions: New Targetable Pathways in Chronic Lymphocytic Leukemia

Clin Lymphoma Myeloma Leuk. 2023 Apr;23(4):232-237. doi: 10.1016/j.clml.2023.01.009. Epub 2023 Jan 20.

Abstract

Regulatory approvals of Bruton tyrosine kinase (BTK) inhibitors and BCL2 inhibitors have transformed the therapeutic paradigm in chronic lymphocytic leukemia (CLL). However, despite significant improvement, treatment discontinuations due to an acquired resistance mutation or intolerance to these agents are common. Those who are refractory and/or intolerant to both these classes of drugs - the "double exposed/refractory" patients - pose a real challenge in clinical practice and are in dire need of novel therapeutic approaches. In this manuscript, we review the ongoing efforts addressing this unmet clinical need including the ongoing development of non-covalent BTK inhibitors, BTK degraders, novel BH3-mimetics, therapeutic antibodies targeting novel antigens and immune cell enabling therapies.

Keywords: BH3-mimetics; Bi-specifics; CAR T; Non-covalent BTK inhibitors; PROTAC.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Drug Resistance, Neoplasm
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell* / genetics
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Agammaglobulinaemia Tyrosine Kinase
  • Antineoplastic Agents
  • Protein Kinase Inhibitors