Fosaprepitant for the Prevention of Nausea and Vomiting in Patients Receiving BEAM or High-Dose Melphalan Conditioning Regimens for Autologous Hematopoietic Stem Cell Transplantation

Abstract

Graft-versus-host-disease (GVHD) is a life threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). The calcineurin inhibitor tacrolimus is commonly used in combination with other immunosuppressants to prevent GVHD; however the optimal serum target concentration for tacrolimus in this population remains unknown. A retrospective review was conducted to determine whether an association exists between tacrolimus concentrations and transplant-related outcomes, specifically acute GVHD, as well as the rate of renal toxicity and mortality. Data from 203 patients who underwent an allogeneic HSCT from a related (n¼95) or unrelated (n¼108) donor between January 1, 2003 and December 31, 2011 at a large academic hospital was analyzed. Sixty-two (31%) patients developed acute GVHD within the first 30 days following allogeneic stem cell transplant. Median tacrolimus concentrations at day 0, 7, 14, and 28 were 11.2, 13.8, 13.5 and 10.2 ng/mL, respectively among those who developed acute GVHD. Patients who did not develop acute GVHD had similar tacrolimus concentrations of 10.4, 13.1, 12.3 and 9.9 ng/mL for the same respective time points. Serum tacrolimus concentrations were similar across all grades of GVHD and there was no correlation between drug concentrations with respect to renal toxicity. Patients who developed renal dysfunction (n¼18) had tacrolimus concentrations similar to the median concentration of the entire cohort, including those who did not experience renal toxicity. Overall mortality among the 203 included patients was 49%. Mortality was higher among patients who developed acute GVHD (55%) than in patients who did not experience the disease (47%). The results of this analysis support previous conclusions that tacrolimus blood concentrations are not associated with acute GVHD within the first 30 days post allogeneic HSCT.Chemotherapy-induced nausea and vomiting (CINV) occurs frequently during hematopoietic stem cell transplantation (HSCT) despite prophylactic therapy with serotonin antagonists and corticosteroids. Aprepitant, an oral neurokinin-1 (NK1) inhibitor, has been considered as add-on prophylactic therapy; however, to date no published studies have investigated the injectable NK1 inhibitor fosaprepitant (FOS) in HSCT. The purpose of this study is to assess the ability of FOS to reduce emesis after BEAM and high-dose melphalan autologous HSCT. The use of a 150 mg fosaprepitant IV x 1 prior to melphalan became standard practice at our institution in the summer of 2012 for BEAM and high-dose melphalan regimens. We performed an IRB approved cohort study comparing patients who prospectively receive FOS to a historical cohort who did not receive FOS. The primary endpoint was overall percentage of patients with no emesis during the assessment period (first day of melphalan through five days after melphalan administration). Secondary endpoints include number of emetic episodes per patient, number of breakthrough antiemetic doses per patient, and complete response rate (no emesis or ...