Pentostatin therapy for steroid-refractory acute graft versus host disease: identifying those who may benefit

Abstract

We report outcomes of 60 patients with steroid-refractory (SR)-aGVHD treated with pentostatin. Almost half (47%) of patients had grade 4 GVHD-22% had stage 3-4 liver GVHD and 51% had stage 3-4 lower gastrointestinal tract (LGI) GVHD. Patients received a median of 3 courses (range, 1-9) of pentostatin. Day 28 overall response rate (ORR) was 33% (n = 20) (complete response 18% (n = 11), partial response 15% (n = 9)). Non-relapse mortality was 72% (95% confidence interval (CI) 61-84%) and overall survival (OS) was 21% (95% CI 12-32%) at 18 months. On univariate analysis, age >60 years (HR 1.9, 95% CI 1.01-3.7, p = 0.045) and presence of liver GVHD (HR 1.9, 95% CI 1.9, 95% CI 1.5-3.3, p = 0.03) were significant predictors of poor OS while patients with LGI GVHD had superior OS than those without (HR 0.4, 95% CI 0.2-0.8, p = 0.01). On stratified analysis, patients <60 years with isolated LGI GVHD had the best outcomes with an ORR of 48% and OS of 42% at 18 months. Among older patients, OS was 14% in those with isolated LGI aGVHD and 0% in others. Pentostatin remains a viable treatment option for SR-aGVHD, especially in patients 60 years or younger with isolated LGI involvement.

Treatment of steroid-refractory graft versus host disease in children

“…The toxicities observed were mostly infectious, but also included 3 cases of autoimmune hemolytic anemia ( 19 ) ( Table 1 ). More studies have been conducted in the adult population, both alone and in combination, with very variable responses, and CR achieved from 13% to 70% ( 23 , 27 , 28 ).…”

Hematopoietic Cell Transplantation, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology

“…173 A large retrospective analysis of 60 patients treated with pentostatin for steroid-refractory aGVHD reported an ORR of 33% and a CR rate of 18%. 174 All patients received pentostatin at a dose of 1.5 mg/m 2 on days 1 to 3, repeated every 2 weeks, for a median of 3 courses. OS at 18 months was 21% and NRM was 72%.…”

“…176 Discrepancies in the results of these studies may be attributed to variability in the patient populations, pentostatin doses and number of treatment cycles, use of additional therapies, or the assessment of treatment response. 174 A phase I dose-escalation study involving 22 patients with steroid-refractory aGVHD reported a high CR rate of 63%. 177 However, late infections observed at the 2 mg/ m 2 /day dose used in the study were considered to be dose-limiting toxicities.…”

<p>Experimental Pharmaceuticals for Steroid-Refractory Acute Graft-versus-Host Disease</p>

“…These agents include traditional oral immunosuppressive agents targeting T-cell activation such as sirolimus or mycophenolate mofetil, and lymphodepletive agents including pentostatin or horse or anti-thymocyte globulin. [13][14][15][16] Based on either Phase I/II study results or retrospective analyses, off-label use of monoclonal antibodies targeting cytokines, such as the anti-TNF-alpha antibody agents infliximab, etanercept, the anti-IL-6 receptor antibody tocilizumab, and anti-IL2 submit your manuscript | www.dovepress.com…”

“…Alpha1-antitrypsin was studied in a single-arm, multicenter study for SR-aGVHD. 36 Enrolled patients were administered AAT at a dose of 60mg/kg per day on Days 1,4,8,12,16,20,24,and 28. In all, 40 patients were enrolled, of which 70% had Grade 3+ aGVHD. By day 28, an ORR of 65% was reported; 35% had achieved a CR at this timepoint.…”