1589. Long term hematopoietic cell transplant outcomes in patients at high risk for cytomegalovirus infections in the era of letermovir
Authors: Febres-Aldana Anthony J , Spallone Amy , Khawaja Fareed , Sassine Joseph , Srinivasan Krithika , Aramburo Oscar Morado , Shigle Terri Lynn , Rondon Gabriella , Ramdial Jeremy , Shpall Elizabeth , Ariza Heredia Ella J , Chemaly Roy F 
Published: December 2022

Abstract

Background
Letermovir (LTV) primary prophylaxis (PP) has reduced the incidence of clinically significant cytomegalovirus infection (CS-CMVi) in allogeneic hematopoietic cell transplant (allo-HCT) recipients. However, it is not clear if these are similar to low-risk recipients (seronegative donor [D-] and recipient [R-]). Prior studies have reported that D-/R- allo-HCT recipients have reduced relapse rates, graft versus host disease (GVHD), and overall mortality. We compared the clinical outcomes of R+ allo-HCT recipients with and without LTV PP to D-/R- allo-HCT recipients.

Methods
This is a single-center study of allo-HCT recipients who underwent transplantation between March 2016 and December 2018. Data on baseline and transplant characteristics were collected. Outcomes included incidence of CS-CMVi, GVHD, all-cause mortality, relapse and NRM. Univariate analysis was performed to compare outcomes in R+ with and without LTV PP cohorts to D-/R- cohort. Categorical and continuous variables were compared using Fisher’s exact test and Wilcoxon rank sum respectively. Survival curves were compared with the log-rank test. Patients who relapsed after transplant were excluded from NRM analysis.

Results
A total of 616 patients underwent an allo-HCT; 124 R+ were on LTV PP, 415 were R+ on no LTV PP as well as the 77 who were CMV D-/R-. When compared to D-/R- group, R+ group who received or not LTV PP were more likely to have AML and ALL, and underwent myeloablative conditioning. The incidence of CS-CMVi was the lowest in the D-/R- group (4%), followed by the R+ on LTV PP (17%), and the highest in the R+ group on no LTV PP (53%) (table 2). Kaplan-Meier survival analysis for NRM 1 year after transplant showed trends towards lower survival in R+ allo-HCT recipients who did not receive LTV PP when compared to the D-/R- group at day 200 and day 360 (p=0.07 vs. p=0.08, respectively). In addition, R+ allo-HCT on LTV PP had similar NRM at day 360 compared to D-/R- (p=0.77) and lower NRM at day 360 compared to R+ allo-HCT on no LTV PP (p=0.0192).

Conclusion
Our study showed a reduction in the rate of CS-CMVi within 48 weeks post HCT in high risk allo-HCT recipients on LTV. NRM was lower in R+ allo-HCT recipients on LTV PP when compared to those without LTV. No difference in NRM was seen between D-/R- allo-HCT and R+ allo-HCT on LTV PP.

Disclosures
Terri Lynn Shigle, PharmD, BCOP, Takeda: Advisor/Consultant Gabriella Rondon, MD, Omeros: Advisor/Consultant Elizabeth Shpall, MD, Adaptimmune: Advisor/Consultant|Affimed: License agreement|Axio: Advisor/Consultant|Bayer Helathcare Pharmaceuticals: Honoraria|Fibroblasts and FibrioBiologics: Advisor/Consultant|Navan: Advisor/Consultant|NY Blood Center: Advisor/Consultant|Takeda: License agreement Ella J. Ariza Heredia, MD, Merck & Co. Inc: Grant/Research Support Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support.