Category: Virology: Studies of Treatment and Prevention of Viral Infections

Poster Session: Virology: Studies of Treatment and Prevention of Viral Infections

1703 - Hematologic Toxicity of Valganciclovir Prophylaxis in Solid Organ Transplant Recipients as a Function of Weight-adjusted Ganciclovir Exposure

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Presenting Author(s)

Toni A. Campanella

Infectious Diseases Clinical Pharmacist
Jefferson Health
Philadelphia, Pennsylvania
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

AR

Amanda Roy

Infectious Diseases Clinical Pharmacist
University of California San Francisco
San Francisco, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
TG

Thomas J. Gintjee

ID Pharmacy Resident
UC Davis Medical Center
Oxnard, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MD

Monica Donnelley

Senior Pharmacist
University of California Davis Medical Center
Sacramento, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Conan MacDougall

Professor of Clinical Pharmacy
University of California San Francisco
San Francisco, CA
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Jason C. Gallagher

Clinical Professor
Temple University
Philadelphia, Pennsylvania
Disclosure: Allergan (Consultant)Astellas (Consultant)Merck (Consultant, Grant/Research Support)Nabriva (Consultant)Qpex (Consultant)scPharmaceuticals (Consultant)Shionogi (Consultant)Spero (Consultant)Tetraphase (Consultant)

Background: Valganciclovir (VGC), an oral prodrug of ganciclovir (GCV), is 60% bioavailable. Manufacturer-recommended doses are adjusted for creatinine clearance (CrCl), but not weight (wt), while GCV doses are adjusted for CrCl and wt. Patients exposed to excess GCV by not wt-adjusting VGC doses may be at risk of hematologic toxicity. The purpose of this study was to investigate the impact of body weight on VGC toxicity in solid organ transplant (SOT) recipients.

Methods: This was a multicenter retrospective study at three academic medical centers of adult SOT recipients who received VGC for CMV prophylaxis between January 2016 and August 2019. The primary outcome was first occurrence of leukopenia within six months post-transplant. The primary predictor was the ratio between the patient’s estimated GCV exposure based on the initial VGC dose prescribed and the equivalent prophylactic GCV dose accounting for the patient’s CrCl and wt (rVGC:GCV).

Results: The study included 231 patients, mostly lung (59%) and kidney (KT, 28%) transplants (Table 1). The rVGCV:GCV was 4.4 (range, 0.6-25.1, SD 4.5), and was significantly higher in KT (7.7 vs 3.0, p < 0.001). Leukopenia occurred in 133 patients (57.5%). After adjustment for type of transplant, rVGC:GCV ratio was not associated with increased odds (OR 0.97, 95% CI 0.91-1.04) or hazard of (HR 0.99, 95% CI 0.95-1.04) leukopenia. Exploratory analysis suggested threshold effects and interaction with transplant type: a rVGCV:VGC of > 3 was associated with time to leukopenia (HR 2.02, 95% CI 1.09-3.74) among non-KT patients but not KT patients (HR 0.99, 95% CI 0.56-1.76) (Figure 1).Table 1

Figure 1

Conclusion: Initial doses of VGC used for SOT CMV prophylaxis are estimated to result in significantly higher GCV exposures than IV GCV doses. A relationship with risk of leukopenia was only seen in non-KT patients, possibly because of rapid recovery of renal function and dose adjustment in KT patients.