Systematic Review and Meta-Analysis of Extracorporeal Photopheresis for the Treatment of Steroid-Refractory Chronic Graft-Versus-Host Disease

Objective The objective of this meta-analysis (MA) was to evaluate the clinical efficacy and safety of extracorporeal photopheresis (ECP) for the treatment of steroid-refractory chronic graft-versus-host disease (SR-cGvHD). Methods A systematic literature review (SLR) was conducted according to PRISMA guidelines. MEDLINE, Embase, Cochrane, DARE and relevant conference proceedings were searched to 19th October 2022 for studies of patients with SR-cGvHD receiving ECP and reporting on efficacy, safety or health-related quality of life (HRQoL) outcomes. A feasibility assessment (FA) was conducted to assess sources of potential between-study heterogeneity in the MA. Random effects MAs were performed for long- and short-term efficacy outcomes including overall survival (OS) and failure-free survival (FFS), and overall response rate (ORR) and skin-specific response, respectively. Timepoint windows were used for ORR (Months 3–4 and Months 6–8) and skin-specific response (Months 2–3 and Months 4–6). A subgroup analysis was also conducted to explore the effect of outcome assessment criteria (National Institutes of Health [NIH] vs non-NIH/unknown). Safety and HRQoL outcomes were poorly reported and therefore were not suitable for MA. Results The SLR identified 627 records, of which 47 unique studies reporting on Therakos ECP machines and with a sample size of ≥10 patients were included; these studies comprised 2,361 patients who received ECP. The majority of studies (n=28) reported on adult only populations (≥18 years). Lines of therapy were poorly reported (n=15) and ranged from 0–≥4 lines of previous treatment. Most studies (n=27) used a retrospective case series study design.Two studies were excluded from analyses as they either did not report cGvHD-specific outcomes or had a crossover study design.For long-term efficacy, the pooled OS rate at Month 12 was 83.97% (95% CI: 77.33–88.94; 14 studies, 704 patients; Figure 1). At Month 60, the OS rate was 57.96% (95% CI: 35.48–77.56; 8 studies, 431 patients). Results from four studies (169 patients) indicated an FFS rate of 60.79% at Month 12 (95% CI: 38.94–79.03; Figure 2).For short-term efficacy, ORR was 45.34% (95% CI: 26.64–65.45) at Months 3–4 (7 studies; 293 patients) and 58.23% (95% CI: 45.04–70.35) at Months 6–8 (13 studies; 540 patients; Figure 3). Subgroup analyses showed no significant difference in ORR between studies utilizing NIH criteria and those utilizing non-NIH criteria. Skin-specific response was 34.86% (95% CI: 13.26-65.21) at Months 2–3 and 54.22% (95% CI: 35.67-71.67) at Months 4-6.There was considerable heterogeneity across all analyses, with I2 values ranging from 65% to 91%. Conclusion This recent systematic review and MA, conducted according to PRISMA guidelines, indicated that ECP results in favorable outcomes in SR-cGvHD, including overall survival, FFS and ORR.