Beclomethasone and Budesonide Are Partially Effective As Sole Therapy for Isolated Gastro-Intestinal Gvhd
Authors: Frairia Chiara , Shapiro Jamie , Kim Jongphil , Pidala Joseph , Ayala Ernesto , Betts Brian C , Fernandez Hugo F , Field Teresa , Kharfan-Dabaja Mohamed , Locke Frederick L , Mishra Asmita , Nishihori Taiga , Ochoa-Bayona Jose L , Perez Lia , Riches Marcie L , Anasetti Claudio 
Published: November 2019

Abstract
Introduction: Gastro-intestinal GVHD (GI GVHD) is a common and severe complication of allogeneic hematopoietic cell transplantation (HCT). Systemic glucocorticoids remain the standard of care for GI GVHD, despite their incomplete efficacy and toxicity. Steroid-sparing activity and improved survival were reported with oral administration of poorly absorbed beclomethasone dipropionate (BDP) in combination with systemic glucocorticoids for upper GI GVHD, and promising results were described with the adjunct of budesonide (BUD) for lower GI GVHD. No data have been reported on BDP or BUD without systemic glucocorticoids. Our team has adopted the practice of administering BDP/BUD without systemic glucocorticoids as fist-line therapy. Here we assess safety and efficacy of our practice in the treatment of isolated GI GVHD.
Methods: We analyzed retrospective data from 297 consecutive patients (pts) with isolated GI GVHD after hematopoietic peripheral blood stem cell transplantation performed at the Moffitt Cancer Center between July 2004 and June 2013. At discretion of the treating physician, patients with upper with or without lower GI GVHD were treated with BDP (5 mg BID or TID orally), BDP plus prednisone (PRED 0.5-2 mg/kg or equivalent glucocorticoid dose), BDP+BUD (3 mg BID or TID orally) or BDP+BUD+PRED. The primary study endpoint was response of GI GVHD after 28 days, defined as complete resolution of all GI symptoms without addition of other immune suppressive (IS) agent(s) or partial reduction of GI symptoms, without resolution and without addition of other IS agent(s). Secondary endpoints were response to treatment after 200 days, chronic GVHD (CGVHD), CMV infection, relapse free survival (RFS), and overall survival (OS). All endpoints were analyzed according to treatment arm (Figure 1). A multivariable model was used to test the association between response after 28 days and treatment arm, after adjusting for primary diagnosis, conditioning regimen, disease status at HCT, pts/donor characteristics, GI GVHD overall grade, GI GVHD site, and albumin level.
Results:
BDP vs. BDP+PRED. Baseline characteristics were well balanced among the BDP (n=90) and BDP+PRED (n=24) groups, including treatment for isolated upper GI GVHD (84% vs. 67%, p=0.08), with the remainder affected by both upper and lower GI GVHD. BDP+PRED showed a significantly higher response of GI GVHD after 28 days compared to BDP (88% vs. 56%, multivariate OR 23, 95% CI 3-161, p=0.002); however there was no significant difference in response after 200 days (50% vs. 33%, univariate p=0.5). There were no significant differences in terms of treatment duration, requirement of additional IS agents, CMV reactivation, CGVHD development, RFS and OS between the two treatment cohorts.
BDP+BUD vs. BDP+BUD+PRED. BDP+BUD+PRED pts (n=53) had more rapid onset of GI GVHD (median 20 vs. 26 days after HCT, p=0.001), higher incidence of lower GI involvement (61% vs. 38%, p=0.008) and higher incidence lower GI stage II-III GVHD (p=0.0004) compared to BDP+BUD pts (n=130). Despite adjusting for these higher risk features by multivariable analyses, BDP+BUD+PRED was associated with a significantly higher response after 28 (90% vs. 75%, multivariate OR 15, 95% CI 3-62, p=0.0003) and 200 days (70% vs. 45%, univariate p=0.0003). There were no significant differences in treatment duration, CMV reactivation, CGVHD development, RFS and OS between the two treatment cohorts.
Conclusions: This retrospective analysis suggests that the addition of systemic PRED to topical BDP/BUD therapy for isolated GI GVHD was associated with a better response after 28 days of treatment. Despite the inferiority in GI GVHD response, there were no differences in secondary endpoints including treatment duration, CMV reactivation, RFS and OS.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.