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Dasatinib Use May Be a Novel Risk Factor for Cytomegalovirus (CMV) Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Year: 2016

Type: article

Abstract: Background. Dasatinib is a second generation tyrosine kinase inhibitor approved for treatment of Philadelphia positive (Ph+) hematological malignancies. CMV infection has been reported rarely in patients with CML treated with dasatinib outside of HSCT, but its role as a risk factor for CMV infection when used after HSCT is not known. Methods. We retrospectively reviewed the records of 109 patients with CML (46) or Ph+ ALL (63) who underwent HSCT from 2005 to 2015. We assessed HSCT characteristics, including recipient CMV seropositivity (CMV R+), acute graft-versus-host disease (aGVHD), dasatinib exposure post-HSCT, and CMV events (infection or disease). Risk factors for CMV events were evaluated using time-dependent Cox modeling. Results. We observed 23 CMV events by one year post-HSCT, only among 63 CMV R+ patients. Dasatinib was used in 21 patients for prevention (5) or treatment (16) of underlying disease molecular relapse. Cumulative incidence of CMV events in dasatinib-exposed CMV R+ patients was 0.75 (95% CI 0.33, 0.99) versus 0.33 (95% CI 0.23, 0.48) in those not exposed. Interestingly, 4 of 8 dasatinib-associated CMV events occurred more than 6 months post-HSCT in patients off immunosuppression and without acute or chronic GVHD, including 1 patient with proven CMV colitis, a median of 85 (range 71–127) days after starting dasatinib. Table: Cox Proportional Hazards Model of CMV Reactivation Among CMV R+ HSCT Patients (n = 63) Adjusting for aGVHD in CMV R+ patients, dasatinib exposure was significantly associated with CMV events (table). Conclusion. Dasatinib use post HSCT is associated with increased risk of CMV reactivation and CMV disease in CMV R+ HSCT patients. Disclosures. F. M. Marty, Alexion: Scientific Advisor, Consulting fee; Ansun: Investigator, Research support; Astellas: Consultant and Investigator, Consulting fee and Research support; Basilea: Conference speaker, Speaker honorarium; Chimerix: Consultant and Investigator, Consulting fee and Research support; Gilead: Consultant and Investigator, Consulting fee and Research support; GlaxoSmithKline: Consultant and Investigator, Consulting fee and Research grant; LFB, S.A.: Consultant, Consulting fee; Merck: Consultant and Investigator, Consulting fee and Research support; Shire: Consultant and Investigator, Consulting fee and Research support; WHISCON: Investigator, Research support; Pfizer: Course speaker, Speaker honorarium; Fate Therapeutics: Scientific Advisor, Consulting fee

Source: Open Forum Infectious Diseases

DOI: 10.1093/ofid/ofw172.1833