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Voriconazole in hematopoietic stem cell transplantation and cellular therapies: Real-world usage and therapeutic level attainment at a major transplant center
Lindsay, J., Krantz, E. M., Morris, J., Sweet, A., Tverdek, F., Joshi, A., Yeh, R., Hill, J. A., Greenwood, M., Chen, S. C., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Voriconazole (VCZ) was one of the first mold-active triazoles available; however, its current use among high-risk hematology populations is unknown as the uptake of posaconazole (PCZ) and isavuconazole (ISZ) increases. OBJECTIVES We evaluated the usage and therapeutic level attainment of VCZ in hematopoietic cell transplant (HCT) and chimeric antigen receptor T cell (CAR-T) therapy patients at our cancer center. STUDY DESIGN Electronic medical records for all adult HCT or CAR-T patients with an order for VCZ, PCZ or ISV between January 1, 2018, and June 30, 2020 were extracted. Clinical characteristics, VCZ indication, trough VCZ levels, and frequency of VCZ initiation from 6 months pre- to 6 months post HCT/CAR-T infusion in consecutive HCT/CAR-T recipients within the study period (infusion between July 1, 2018, and January 1, 2020) were assessed. The association between relevant clinical characteristics and the attainment of sub- or supratherapeutic levels was also evaluated. RESULTS Of 468 patients prescribed mold-active triazoles, 256 (54.7%) were prescribed VCZ, 324 (69.2%) PCZ, and 60 (12.8%) ISZ; 152/468 (32.5%) treatment regimens were sequentially modified to alternate mold-active triazoles. Among consecutive HCT and CAR-T recipients at our center, evaluated 6 months pre- or post- HCT/ CAR-T, VCZ was commonly initiated pre- or post-allogeneic HCT (102/381, 26.8%), with most use in the first 30 days post stem cell infusion (40/381, 10.5%); VCZ use was less common in autologous HCT (13/276, 4.7%) and CAR-T (10/153, 6.5%). Of 223 VCZ orders that met inclusion for analysis, indications included empiric treatment in 108/223 (48.4%), directed therapy in 25/223 (11.2%), primary prophylaxis in 69/223 (30.9%) and secondary prophylaxis in 21/223 (9.4%). Of 223 eligible VCZ patients, 144 (64.6%) had at least one VCZ level measured during the study period; 75/144 (52.1%) had a therapeutic VCZ level (1.0-5.5mg/L) at the first measurement (median 2.8mg/L [range 0.1 - 13.5]) at a median of 6 days of therapy, with 26.4% subtherapeutic and 21.5% supratherapeutic; 46/88 (52.3%) were therapeutic at the second measurement (2.1mg/L [0.1 - 9.9]) at a median of 17 days of therapy; and 33/48 (68.8%) at the third (2.3mg/L [0.1 - 7.7]) at a median of 29 days. In multivariable analysis of factors associated with sub- or supratherapeutic levels (body mass index ≥30, concurrent omeprazole use, concurrent letermovir use, indication for VCZ, history/timeframe of HCT), the only significant association was lower odds of a supratherapeutic VCZ level among those undergoing HCT within the previous 30 days compared to those without a history of HCT. CONCLUSIONS VCZ continues to remain an important option in the treatment and prevention of invasive fungal infections in an era when alternative oral mold-active triazoles are available. In spite of long-standing experience with VCZ prescribing, therapeutic level attainment remains a challenge.