Dasatinib combined with interferon-alfa induces a complete cytogenetic response and major molecular response in a patient with chronic myelogenous leukemia harboring the T315I BCR-ABL1 mutation.
Mutations of BCR-ABL1 are observed in 50% of patients with imatinib-resistant chronic myeloid leukemia (CML). The T315I mutation is resistant to imatinib and second-generation tyrosine kinase inhibitors (TKIs). We report the case of a 57-year-old man diagnosed with CML in 2003 in whom imatinib therapy failed after which he acquired the T315I mutation. He was treated sequentially with an anti-T315I-specific agent, KW-2449, that led to eradication of the mutation without any further improvement. Subsequent introduction of combination therapy that included dasatinib and pegylated interferon led to the achievement of a sustained complete cytogenetic and major molecular response (MMR). This case illustrates the benefit of combination therapy that includes a TKI and a second agent with a different mechanism of action, either sequentially (TKI followed by KW-2449) or concomitantly (TKI + interferon), in eradicating resistant disease with the T315I clone.
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. meg.cornel@gmail.com
A Megan
AM
Cornelison
Mary-Alma
MA
Welch
Charles
C
Koller
Elias
E
Jabbour
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D003582:Cytogenetics / Q000379:methods; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011743:Pyrimidines / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage
D016898:Interferon-alpha; D011743:Pyrimidines; D013844:Thiazoles; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib