Advances in the treatment of relapsed/refractory chronic lymphocytic leukemia

Ann Hematol. 2017 Jul;96(7):1185-1196. doi: 10.1007/s00277-017-2982-1. Epub 2017 Apr 7.

Abstract

Treatment of chronic lymphocytic leukemia (CLL) has advanced with the introduction of chemoimmunotherapy (CIT) agents that have improved the outcomes of frontline therapy. However, most treated patients will relapse and require subsequent therapy. This review focuses on recent advances in the treatment of relapsed or refractory CLL. Until recently, treatment options for relapsed CLL were of limited efficacy. Retreatment with fludarabine, cyclophosphamide, and rituximab (FCR) was recommended for patients with a durable response to first-line FCR, although acquired genetic aberrations, impaired marrow reserve, and comorbidities often made this suboptimal therapy for many patients. New options include two agents targeting B cell receptor (BCR) signaling pathways (ibrutinib and idelalisib) and a B cell lymphoma-2 (BCL-2) inhibitor (venetoclax). Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative option for younger patients with a suitable donor.

Keywords: CLL; HSCT; Ibrutinib; Idelalisib; Venetoclax.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Drug Resistance, Neoplasm
  • Drug Therapy / methods*
  • Drug Therapy / trends
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / trends
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Piperidines
  • Purines / therapeutic use
  • Pyrazoles / therapeutic use
  • Pyrimidines / therapeutic use
  • Quinazolinones / therapeutic use
  • Recurrence
  • Sulfonamides / therapeutic use
  • Transplantation, Homologous

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Piperidines
  • Purines
  • Pyrazoles
  • Pyrimidines
  • Quinazolinones
  • Sulfonamides
  • ibrutinib
  • Adenine
  • venetoclax
  • idelalisib