2286. Dasatinib Use May Be a Novel Risk Factor for Cytomegalovirus (CMV) Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Session: Poster Abstract Session: Transplants: CMV and Transplantation
Saturday, October 29, 2016
Room: Poster Hall
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.

Adjusting for aGVHD in CMV R+ patients, dasatinib exposure was significantly associated with CMV events (Table).

Table. Cox proportional hazards model of CMV reactivation among CMV R+ HSCT patients (n=63)

Risk Factor

Univariate hazard ratio

(95% CI)

p-value

Multivariate hazard ratio

(95% CI)

p-value

aGVHD, grade II-IV

2.08 (0.90, 4.83)

0.09

2.05 (0.88, 4.80)

0.095

Dasatinib Use

7.95 (1.89, 33.5)

0.005

7.65 (1.84, 31.7)

0.005

Conclusion: Dasatinib use post HSCT is associated with increased risk of CMV reactivation and CMV disease in CMV R+ HSCT patients. 

Daniel Prestes, MD, Infectious Diseases, Brigham and Women's Hospital/Harvard Medical School, Boston, MA/Hospital Emilio Ribas, Sao Paulo, Brazil/Hospital Sirio Libanes, Sao Paulo, Brazil, Boston, MA, Esther Arbona, MD, Infectious Disease, Brigham & Women's Hospital, Boston, MA, Alexandra Nevett Fernandez, MD, Brigham and Women Hospital/Harvard Medical School, Boston, MA, Sophia Koo, MD, Infectious Diseases, Dana-Farber Cancer Institute, Boston, MA, Vincent Ho, MD, Brigham and Women's Hospital/Dana-Farber-Cancer-Institute/Harvard Medical School, Boston, MA, John Koreth, MD, Brigham and Women's Hospital/Dana-Farber-Cancer Institute/Harvard Medical School, Boston, MA, Sarah P. Hammond, MD, Infectious Diseases, Brigham and Women's Hospital, Boston, MA, Nicolas Issa, MD, Division of Infectious Diseases, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Lindsey Baden, MD, Brigham and Women's Hospital, Infectious Diseases/Dana-Farber-Cancer Institute/Harvard Medical School, Boston, MA and Francisco M. Marty, MD, FIDSA, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA

Disclosures:

D. Prestes, None

E. Arbona, None

A. Nevett Fernandez, None

S. Koo, None

V. Ho, None

J. Koreth, None

S. P. Hammond, None

N. Issa, None

L. Baden, None

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

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