Extracorporeal Photopheresis (ECP) in the Era of New Chronic Graft-Versus-Disease (GVHD) Therapies

Despite significant advances in its management, chronic GVHD remains a major cause of morbidity and mortality among patients receiving allogeneic hematopoietic cell transplantation (Allo). Frontline therapy with systemic corticosteroids alone or in combination with sirolimus or a calcineurin inhibitor is often inadequate as 70% of patients require subsequent therapy due to lack of efficacy or intolerance to side effects (Carpenter el al, Hematologic 2018). In the last few years, several new drugs were approved for cGVHD including Ibrutinib, Ruxolitinib and Belumosudil with response rates reaching >70%. These drugs, however, carry significant adverse events, compliance requirements and financial burden.

Extracorporeal photopheresis has been a widely adopted modality of therapy for chronic GVHD failing or intolerant to steroids. ECP has a very well tolerated safety profile and can be combined with other chronic GVHD therapies without adding significant toxicity. The role of ECP in the recent era of new chronic GVHD drugs has not been well reported. Here, we report on our experience of 289 consecutive chronic GVHD patients who were treated at our center using ECP (n=87) or no ECP ( n=202) and received their transplant between 2015 and 2022. Frontline therapy at our center is steroids plus sirolimus or calcineurin inhibitor +/- rituximab. Subsequent therapies are based on organs involved, side effects, patient compliance, and physician preference. ECP was used as second line in 16 and third line and beyond in 71 patients. All patients received standardized antimicrobial prophylaxis, routine response assessment monthly and a detailed symptom score assessment every 3 months. Patients were assessed by a single GVHD nurse provider to document severity and response based on 2014 NIH consensus GVHD criteria. We compared both groups in terms of overall response rate, changes in NIH symptom score and survival endpoints. Patients characteristics were as follows: median age 54(18-76), male 57%, most common diagnosis ( AML 34%, ALL 18%, MDS 23%, other 25%), donor ( haplo 35%, MRD 32%, MUD 32%), cell source ( PBSC 90%), disease risk DF DRI (low/intermediate 77%, high/very high 23%) and HCT-CI 0-2 (40%). Both groups (ECP and no ECP) had similar baseline characteristics with median onset to chronic GVHD of 261 vs 246 days (p=0.95). Severity of chronic GVHD was similar between both groups mild (37% vs 50%), moderate (45% vs 38%) and severe (17% vs 12%), p=0.10. patients who received ECP had a higher number of organs involved at onset of GVHD (2.2 organs vs 1.8, p=0.02) compared to no ECP. Most common organs involved were skin (42%), mouth (67%), eyes (36%), liver (21%), GI (16%), musculoskeletal (9%) and lung (5%). The distribution of organ involvement was significant for more skin (50% vs 38%) in ECP vs no ECP. Patients received different medications for chronic GVHD including tacrolimus (n=199), sirolimus (n=143), rituximab 9 n=212), Steroids (n=289), Ruxolitinib (n=83), Belumosudil (n=43), ibrutinib (n=39), Imatinib ( n=24), budesonide (n=47) and infliximab (n=21). The overall response and complete response rates at 6 months were 76% and 36% for ECP vs 68% and 46% for no ECP. There was no difference in ECP response if it was used before (n=49), concomitant (n=12) or after (n=36) Ruxolitinib and/or Belumosudil. The NIH symptom score reduction at 6 months was higher in ECP (1.95) compared to no ECP (1.42). There was no difference in 3 year OS (81.5 vs 83.4%), DFS ( 73% vs 78%), Relapse ( 16% vs 13%) and NRM (13% vs 10%), p=NS for ECP and no ECP groups.

In conclusion, our data shows that ECP alone or in combination with other treatments is highly effective treatment for chronic GVHD with comparable responses and higher reduction in GVHD total symptom score compared to non-ECP modalities.