Journal-based CME Course: Chronic Myeloid Leukemia – A Review

Activity ID

13915

Expires

March 17, 2028

Format Type

Journal-based

CME Credit

1

Fee

$30

CME Provider: JAMA

Description of CME Course

Importance  Chronic myeloid leukemia (CML) has an annual incidence of 2 cases per 100 000 people and is newly diagnosed in approximately 9300 individuals per year in the US. Approximately 150 000 people in the US and 5 million worldwide have CML.

Observations  Chronic myeloid leukemia is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome, which is defined by the BCR::ABL1 oncogene that develops after fusion of the ABL1 proto-oncogene to the constitutively active BCR gene. Approximately 90% of people with CML present with an indolent chronic phase of CML, defined as blasts of less than 10% in the blood or bone marrow, absence of extramedullary evidence of leukemia, basophils of less than 20%, and platelet counts of 100 to 1000 × 10⁹/L. The most advanced stage is CML blastic phase (CML-BP), characterized by the World Health Organization as 20% or more blasts/immature cells and by the MD Anderson Cancer Center and European LeukemiaNet as 30% or more. Approximately 1% to 2% of patients with CML present with CML-BP. Since 2000, first-generation tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1, such as imatinib, and second-generation TKIs, such as bosutinib, dasatinib, and nilotinib, have improved CML-related mortality from 10% to 20% per year to 1% to 2% per year, such that patients with CML have survival rates similar to those of a general age-matched population. Six BCR::ABL1 TKIs have been approved by the US Food and Drug Administration, including 5 that are first-line treatment (imatinib, dasatinib, bosutinib, nilotinib, and asciminib) and 5 approved for treatment after disease progression despite initial therapy (dasatinib, bosutinib, nilotinib, ponatinib, asciminib). Effects on improved survival are similar with all TKIs, although more patients are able to promptly achieve and maintain BCR::ABL1 clearance with second- and third-generation TKIs. Medication adherence is important to maintain treatment responsiveness. All TKIs are associated with hematologic toxicity, such as myelosuppression, with additional agent-specific adverse effects, such as pleural effusion (dasatinib), arterio-occlusive events such as myocardial infarction, stroke, and peripheral artery disease (nilotinib, ponatinib), gastrointestinal disturbance (bosutinib), or increased amylase and lipase with pancreatitis (ponatinib, asciminib, nilotinib). These adverse effects should be considered when selecting a TKI. Allogeneic hematopoietic stem cell transplant is a reasonably safe therapy, with cure rates ranging from 20% to 60% based on the stage of CML at the time of transplant. Stem cell transplant is reserved for patients with CML who do not respond to second-generation TKIs, those with intolerance to multiple TKIs, or those with accelerated-phase CML or CML-BP.

Conclusions and Relevance  Chronic myeloid leukemia is a myeloproliferative neoplasm that can typically be effectively treated with TKIs, improving survival similar to that of a general age-matched population. Many patients require continuous TKI therapy. Therefore, TKI therapy should be selected with consideration of adverse effects, and patients should be helped to maximize adherence to TKI treatment.

Disclaimers

1. This activity is accredited by the American Medical Association.
2. This activity is free to AMA members.

Register for this Activity