Chronic Myelogenous Leukemia (CML) Medication

Updated: Jun 23, 2017
  • Author: Emmanuel C Besa, MD; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP  more...
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Medication

Medication Summary

The medications used for patients with chronic-phase chronic myelogenous leukemia (CML) aim at delaying the onset of the accelerated or blastic phase. This has traditionally included a myelosuppressive agent to achieve hematologic remission, but more effective drugs—successively, interferon alfa then and targeted therapy with tyrosine kinase inhibitors such as imatinib mesylate, have gained greater importance. Chemotherapy may be used, particularly in preparation for bone marrow or hematopoietic stem cell transplantation.

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Antineoplastic Agents

Class Summary

To control the underlying hyperproliferation of the myeloid elements, a myelosuppressive agent is used to bring down WBC counts and, occasionally, elevated platelet counts. Spleen size correlates with WBC counts, and it shrinks as WBC counts approach the reference range. Also, intermediate and myeloblast cells disappear from the circulation.

Hydroxyurea (Hydrea, Droxia)

Hydroxyurea is an inhibitor of deoxynucleotide synthesis. This agent is used to control high WBC counts during induction with imatinib; it is discontinued once control is established. Hydroxyurea is less leukemogenic than alkylating agents such as busulfan, melphalan (Alkeran), or chlorambucil. Myelosuppressive effects last a few days to a week and are easier to control than with alkylating agents; busulfan is associated with prolonged marrow suppression and can cause pulmonary fibrosis.

Busulfan (Myleran, Busulfex)

Busulfan is a potent cytotoxic drug that, at recommended dosage, causes profound myelosuppression. As an alkylating agent, the mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Omacetaxine (Synribo)

Omacetaxine is a protein synthesis inhibitor that is independent of direct Bcr-Abl binding. It binds to the A-site cleft in the peptidyl-transferase center of the large ribosomal subunit from a strain of archaeabacteria. It is indicated for chronic- or accelerated-phase CML with resistance and/or intolerance to ≥ 2 tyrosine kinase inhibitors.

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Tyrosine Kinase Inhibitors

Class Summary

Tyrosine kinase inhibitors elicit strong inhibition of tyrosine kinase activity of the BCR/ABL abnormality in all phases of CML.

Imatinib mesylate (Gleevec)

Imatinib is specifically designed to inhibit the tyrosine kinase activity of bcr-abl kinase in Ph1-positive leukemic CML cell lines. It is well absorbed after oral administration, with maximum concentrations achieved within 2-4 hours. Elimination is primarily in feces in the form of metabolites.

Dasatinib (Sprycel)

Dasatinib is a multiple tyrosine kinase inhibitor. It inhibits growth of cell lines overexpressing BCR/ABL. It has been able to overcome imatinib resistance resulting from BCR/ABL kinase domain mutations.

Dasatinib was originally approved in 2006 by the US Food and Drug Administration (FDA) for the treatment of adult patients with chronic-phase CML resistant or intolerant to prior therapy that included imatinib. In October 2010, the FDA extended approval to include the treatment of newly diagnosed adult patients with Ph1-positive chronic-phase CML.

Nilotinib (Tasigna)

Nilotinib inhibits BCR/ABL kinase. It was originally approved in 2007 by the FDA for the treatment of adult patients with chronic-phase CML resistant or intolerant to prior therapy that included imatinib. In June 2010, the FDA extended approval to include the treatment of newly diagnosed adult patients with Ph1-positive chronic-phase CML.

Bosutinib (Bosulif)

Bosutinib is a tyrosine kinase inhibitor. It inhibits the Bcr-Abl kinase that promotes CML, and it also inhibits SRc-family kinases, including Src, Lyn, and Hck. It inhibits 16 of 18 imatinib-resistant forms of Bcr-Abl expressed in murine myeloid cell lines, but does not inhibit T315I and V299L mutant cells.

Ponatinib (Iclusig)

Ponatinib is a kinase inhibitor indicated for patients with CML or Ph+ ALL that is resistant or intolerant to prior tyrosine kinase inhibitor therapy, including those with the T315I mutation. Because of its high risk for thromboembolic events, it is indicated for patients with T315I-positive, Ph+ ALL for whom no other TKI therapy is indicated.

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Interferons

Class Summary

Alfa, beta, and gamma are the 3 types of interferons known to date. The alfa group has been found to inhibit propagation of Ph-positive hematopoietic clone, allowing return of normal cells in bone marrow.

Peginterferon alfa 2a (Pegasys)

Alfa, beta, and gamma are the 3 types of interferons known to date. The alfa group has been found to inhibit propagation of Ph1-positive hematopoietic clones, allowing return of normal cells in bone marrow.

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