Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: current treatments and future perspectives

Clin Adv Hematol Oncol. 2018 Mar;16(3):216-223.

Abstract

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) accounts for approximately one-fourth of cases of adult ALL. It typically presents with an aggressive clinical course, responds poorly to standard chemotherapy, and carries a high risk for relapse. The landscape of Ph+ ALL therapy has changed favorably since the development of tyrosine kinase inhibitors (TKIs). With the successful incorporation of TKIs into chemotherapy regimens, remissions occur more frequently and patients live longer. Imatinib was the first TKI that targeted the BCR-ABL1 oncoprotein in Ph+ ALL. Since then, nilotinib, dasatinib, bosutinib, and ponatinib have been developed. Despite the significant progress that has been made in inducing remission, frequent relapses remain a challenge, especially among those with resistant BCR-ABL1 mutations. Still, the therapeutic armamentarium of ALL therapy is expanding at a breathtaking pace today compared with a decade ago. Novel drugs, such as potent later-generation TKIs, antibody-drug conjugates, bispecific monoclonal antibodies, and chimeric antigen receptor T-cell therapies, are being developed and investigated in patients with Ph+ ALL. In this review, we summarize the current treatment options for Ph+ ALL and highlight the therapies that may become the standard of care in the near future.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm, Residual
  • Philadelphia Chromosome
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Fusion Proteins, bcr-abl