Evaluation of Melphalan Exposure in Lymphoma Patients Undergoing BEAM and Autologous Hematopoietic Cell Transplantation

Parastoo B Dahi, Andrew Lin, Michael Scordo, Jessica R Flynn, Sean M Devlin, Josel D Ruiz, Lauren DeRespiris, Dean Carlow, Christina Cho, Oscar B Lahoud, Miguel-Angel Perales, Craig S Sauter, Jan Jaap Boelens, Rick Admiraal, Sergio A Giralt, Gunjan L Shah

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

High-dose melphalan is one of the main cytotoxic DNA alkylating agents and is used in many transplantation conditioning regimens. Studies have shown a wide range of drug exposure when a traditional weight-based dose of melphalan is used. The optimal melphalan dose in BEAM (carmustine, etoposide, cytarabine, and melphalan), which results in maximum efficacy with acceptable toxicity, is unknown. In this pharmacokinetic (PK) analysis of 105 patients with lymphoma undergoing treatment with BEAM and autologous hematopoietic cell transplantation, we initially estimated melphalan exposure as area under the curve (AUC) by a noncompartmental analysis and subsequently compared it with a newly developed 2-compartment population-PK model. The 2 models correlated closely with each other. We found that the traditional fixed weight-based dosing of propylene glycol-free (captisol-enabled) melphalan in BEAM results in a wide variation in exposure as estimated by both models. Higher melphalan exposure was significantly associated with increased metabolic toxicities but did not seem to impact progression-free survival. Although our study suggests a melphalan AUC of 8 mg·h/L as a potential target in BEAM, larger prospective studies using personalized PK-directed melphalan dosing are needed to determine the optimal melphalan exposure in lymphomas.

Originele taal-2Engels
Pagina's (van-tot)485.e1-485.e6
TijdschriftTransplantation and Cellular Therapy
Volume28
Nummer van het tijdschrift8
DOI's
StatusGepubliceerd - aug. 2022

Vingerafdruk

Duik in de onderzoeksthema's van 'Evaluation of Melphalan Exposure in Lymphoma Patients Undergoing BEAM and Autologous Hematopoietic Cell Transplantation'. Samen vormen ze een unieke vingerafdruk.

Citeer dit