Toxicities Of Cmv Preemptive Therapy In The First 100 Days After Allogeneic Hematopoietic Cell Transplantation (Hct): A Real-World Study At Memorial Sloan Kettering Cancer Center (Mskcc)

BackgroundCytomegalovirus (CMV) is the most common viral infection after HCT. Current antivirals used for preemptive therapy (PET) effectively prevent CMV disease, but their use is limited by toxicities. We examined real-world utilization patterns of PET and associated toxicities in HCT recipients at high risk (HR) and low risk (LR) for CMV through day (D) 100 post HCT.MethodsAdult, CMV-seropositive first bone-marrow or peripheral blood HCT recipients from January 1, 2015 through December 31, 2017, routinely monitored by quantitative CMV PCR (Taqman, Roche) were analyzed. PET utilization including types and sequence of antivirals, dose and duration, and reasons for discontinuation through D 100 were extracted from medical records. HR included T-cell depleted HCT or conventional mismatched or haploidentical HCT. All other were LR. Descriptive statistics are reported.ResultsOf 232 patients (pts), 121 (52%) received PET including 40 LR and 81 HR. PET started at a median 35 D post HCT [HR vs. LR: 32 vs. 39, P<0.0001]. CMV viral load (VL) at PET initiation was <137 IU/mL in 23 pts; and median of 475 IU/ml in 98 pts. Valganciclovir was the most common 1st PET (55%), followed by foscarnet (26%) and ganciclovir (19%). 65 pts completed planned 1st PET regimen; 33.1% discontinued 1st PET due to either clinical toxicity (20.7%) or lack of virologic response (12.4%). Subsequently, 2nd and 3rd PET agents were administered to 46.1% and 20.7% of pts respectively. Median duration of PET was 37 days [HR vs. LR: 41 vs. 30.5, P=0.011].ConclusionsValganciclovir was the preferred first line PET agent. HR pts had earlier initiation and longer PET duration. 1st PET discontinuation/change due to clinical or laboratory defined toxicity occurred commonly with similar frequency between HR and LR. Our findings support the need for more effective and safer PET alternatives for HCT recipients. Cytomegalovirus (CMV) is the most common viral infection after HCT. Current antivirals used for preemptive therapy (PET) effectively prevent CMV disease, but their use is limited by toxicities. We examined real-world utilization patterns of PET and associated toxicities in HCT recipients at high risk (HR) and low risk (LR) for CMV through day (D) 100 post HCT. Adult, CMV-seropositive first bone-marrow or peripheral blood HCT recipients from January 1, 2015 through December 31, 2017, routinely monitored by quantitative CMV PCR (Taqman, Roche) were analyzed. PET utilization including types and sequence of antivirals, dose and duration, and reasons for discontinuation through D 100 were extracted from medical records. HR included T-cell depleted HCT or conventional mismatched or haploidentical HCT. All other were LR. Descriptive statistics are reported. Of 232 patients (pts), 121 (52%) received PET including 40 LR and 81 HR. PET started at a median 35 D post HCT [HR vs. LR: 32 vs. 39, P<0.0001]. CMV viral load (VL) at PET initiation was <137 IU/mL in 23 pts; and median of 475 IU/ml in 98 pts. Valganciclovir was the most common 1st PET (55%), followed by foscarnet (26%) and ganciclovir (19%). 65 pts completed planned 1st PET regimen; 33.1% discontinued 1st PET due to either clinical toxicity (20.7%) or lack of virologic response (12.4%). Subsequently, 2nd and 3rd PET agents were administered to 46.1% and 20.7% of pts respectively. Median duration of PET was 37 days [HR vs. LR: 41 vs. 30.5, P=0.011]. Valganciclovir was the preferred first line PET agent. HR pts had earlier initiation and longer PET duration. 1st PET discontinuation/change due to clinical or laboratory defined toxicity occurred commonly with similar frequency between HR and LR. Our findings support the need for more effective and safer PET alternatives for HCT recipients.