Last reviewed: December 2018
Last updated: December  2018
07 Dec 2018

Reversible posterior leukoencephalopathy syndrome in patients receiving ponatinib

Healthcare professionals are advised that there is a risk of reversible posterior leukoencephalopathy syndrome (RPLS, also known as posterior reversible encephalopathy syndrome) in patients taking ponatinib.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has advised that:

  • A routine European review suggests that the risk could affect up to 1 in 100 people who are taking the medicine.

  • Treatment should be interrupted if RPLS is confirmed, and resumed only when it has resolved and if the benefits of continuing treatment outweigh the risk of RPLS.

  • Patients receiving ponatinib should be advised to contact their healthcare professional immediately if they develop sudden-onset severe headache, confusion, seizures, or vision changes.

RPLS is a neurologic disorder that can present with seizure, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurologic disturbances.

The MHRA advice follows a European post-marketing review of ponatinib that identified five cases of RPLS; two cases improved after treatment withdrawal, and did not reappear when restarted at a lower dose. RPLS is included in the warnings/precautions section of the US prescribing information.

Ponatinib (a tyrosine kinase inhibitor) is indicated for adults with chronic-phase, accelerated-phase, or blast-phase chronic myelogenous leukemia who are resistant or unsuitable for treatment with other tyrosine kinase inhibitors, or who have the T315I mutation.

See Management: approach See Management: treatment algorithm

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • splenomegaly
  • malaise
  • night sweats
  • fever
  • excessive bleeding
  • bone pain

Other diagnostic factors

  • weight loss
  • petechiae, ecchymoses, or easy bruising
  • infection
  • abdominal pain
  • visual changes
  • focal neurologic signs
  • priapism
  • confusion or stupor

Risk factors

  • history of chronic myelogenous leukemia (CML)
  • exposure to ionizing radiation
  • exposure to alkylating chemotherapeutic agents

Diagnostic investigations

Investigations to consider

  • peripheral blood smear
  • bone marrow aspiration and biopsy
  • karyotype
  • fluorescent in situ hybridization
  • quantitative PCR
  • serum leukocyte alkaline phosphatase
  • serum vitamin B12
  • T315I gene mutation test
Full details

Treatment algorithm

Contributors

Authors VIEW ALL

Carlos Palacio

Professor of Medicine

University of Florida College of Medicine

Jacksonville

FL

Disclosures

CP declares that he has no competing interests.

Associate Professor of Medicine

University of Florida College of Medicine

Jacksonville

FL

Disclosures

FR declares that she has no competing interests.

Peer reviewers VIEW ALL

Assistant Professor of Human Cancer Genetics

Ohio State University

Columbus

OH

Disclosures

DP declares that he has no competing interests.

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