Chronic Myelogenous Leukemia (CML) Medication

Updated: Aug 31, 2022
  • Author: Emmanuel C Besa, MD; Chief Editor: Sara J Grethlein, MD, MBA, FACP  more...
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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 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.


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)

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. It is used in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for CML.

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.


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 indicated for treatment of Ph+ CML in chronic phase (newly diagnosed) in adults and children and treatment of Ph+ CML in blast crisis, accelerated phase, or chronic phase after failure of interferon-alfa therapy.

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 is indicated for newly diagnosed adults with Philadelphia chromosome-positive (Ph+) CML in chronic phase, adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib, adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy, and pediatric patients with Ph+ CML in chronic phase.

Nilotinib (Tasigna)

Nilotinib is a selective tyrosine kinase inhibitor that targets BCR-ABL kinase, c-KIT and platelet derived growth factor receptor (PDGFR). Nilotinib inhibits BCR-ABL mediated proliferation of leukemic cell lines by binding to the ATP-binding site of BCR-ABL and inhibiting tyrosine kinase activity. Nilotinib has activity in imatinib-resistant BCR-ABL kinase mutations. It is indicated in adults for the treatment of newly diagnosed Ph+ CML and chronic or accelerated phase Ph+ CML resistant to or intolerant to prior therapy that included imatinib. Also indicated in pediatric patients (≥1 year) for the treatment of newly diagnosed Ph+ CML and chronic phase Ph+ CML resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy.

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. This kinase inhibitor indicated for the treatment of adult patients with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy. It also indicated for newly-diagnosed chronic phase Ph+ CML.

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.

Asciminib (Scemblix)

Asciminib is a kinase inhibitor that binds to the ABL-myristoyl pockets and inhibits ABL1-kinase activity. It has been granted accelerated approval for CML in chronic-phase Ph+ CML (Ph+ CML-CP) in adults who have been previously treated with 2 or more tyrosine kinase inhibitors. It is also indicated for Ph+ CML-CP in adults with T3151 mutation.


FGFR Inhibitors

Class Summary

Consider for relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement.

Pemigatinib (Pemazyre)

Orally bioavailable inhibitor of the FGFR types 1, 2, and 3 (FGFR1/2/3). Pemigatinib inhibits FGFR 1/2/3 phosphorylation and signaling, and decreases cell viability in cancer cell lines with activating FGFR amplifications and fusions. It is indicated for relapsed or refractory MLNs in adults with FGFR1 rearrangement. 



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.