1589. Long term hematopoietic cell transplant outcomes in patients at high risk for cytomegalovirus infections in the era of letermovir. (15th December 2022)

• Record Type: Journal Article
• 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
• Is Part Of: Open forum infectious diseases. Volume 9:(2022)Supplement 2
• Publication Date: 2022-12-15
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofac492.112
• Languages: English
• ISSNs: 2328-8957

Abstract

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). Table 1. Patient characteristics and demographics * P< 0.05 Abbreviations: D: Donor; R: Recipient; LTV: Letermovir; ALL: acute lymphoblastic leukemia; AML: Acute myeloid leukemia; CLL/SLL: Chronic lymphoblastic leukemia/small lymphocytic leukemia; CML: chronic myeloid leukemia; CMML: Chronic myelomonocytic leukemia; MDS: myelodysplastic syndrome; MF: myelofibrosis; NHL: non-Hodgkin lymphoma ; HCT: hematopoietic cell transplantation; MRD: Match related donor; MUD: match unrelated donor: MMUD: mismatched unrelated donor; ATG: antithyroglobulin; Post-Cy: post cyclophosphamide; CMV: cytomegalovirus; GCV: ganciclovir. Table 2. Post transplant outcomes ±A total of 106 patients relapased prior to 48 weeks, and were excluded from analysis * P< 0.05 Abbreviations: D: Donor; R: Recipient; LTV: Letermovir; CS-CMVi: Clinically significant CMV infection; GVHD: Graft versus host disease. Figure 1. Survival curve (Kaplan-Merier) after transplant for CMV R-/D- (blue), R+ without LTV (green), and R+ with LTV (red) within the first year after transplant. Patients with relapse disease were censored. *p<0.05 Abbreviations: D: Donor; R: Recipient; LTV: Letermovir. 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.