Extracorporeal photopheresis in acute and chronic steroid‑refractory graft-versus-host disease: an evolving treatment landscape

Abstract

Patients with steroid-refractory graft-versus-host disease (GvHD) are known to have a poor prognosis and for decades no approved drug has been available to treat this serious condition. Although ruxolitinib, a selective Janus kinase (JAK)1/2 inhibitor demonstrated significantly higher response rates in randomized trials compared to the best available therapy, and thus, is of benefit in both acute as well as chronic GvHD, there is an urgent medical need to improve results, such as durability of responses, response in eye, liver and lung manifestations and reduction of infectious complications. In this “Review” article we would like to offer strategies for improving treatment results in patients with steroid-refractory GvHD by combining ruxolitinib with extracorporeal photopheresis (ECP), a leukapheresis-based immunomodulatory treatment frequently applied in T-cell mediated immune disease including GvHD. Our article explores key published evidence supporting the clinical efficacy of both ruxolitinib and ECP in the treatment of GvHD and highlights their potentially complementary mechanisms of action.

Ruxolitinib is highly effective in steroid-resistant graft-versus-host disease. Real world data from a single center

“…According to other reports, RUX is not only effective as a salvage therapeutic option [10,11,12] but can also be successfully used as a steroid sparing agent [13]. Moreover, one may speculate that its efficacy may be even higher when combined with ECP due to increasing number of regulatory T-cells [14,15].…”

Wirkweise, Indikationen und Therapieempfehlungen der extrakorporalen Photopherese (ECP)

“…2,35 Aufgrund des ausgezeichneten Sicherheitsprofils von ECP und der bisher nicht vorhandenen Wechselwirkungen mit anderen Arzneimitteln wird ECP auch in Kombination mit Ruxolitinib als mögliche Therapieoption befürwortet. 49 Die Vorteile der ECP gegenüber den pharmakologischen Zweitlinientherapien liegen in der guten Verträglichkeit, der fehlenden Organschädigung, der geringeren Anzahl opportunistischer Infektionen und der geringeren Anzahl von GvHD-Rezidiven.…”

“…Die Vorteile der ECP gegenüber den pharmakologischen Zweitlinientherapien liegen in der guten Verträglichkeit, der fehlenden Organschädigung, der geringeren Anzahl opportunistischer Infektionen und der geringeren Anzahl von GvHD‐Rezidiven 2,35 . Aufgrund des ausgezeichneten Sicherheitsprofils von ECP und der bisher nicht vorhandenen Wechselwirkungen mit anderen Arzneimitteln wird ECP auch in Kombination mit Ruxolitinib als mögliche Therapieoption befürwortet 49 Die Vorteile der ECP gegenüber den pharmakologischen Zweitlinientherapien liegen in der guten Verträglichkeit, der fehlenden Organschädigung, der geringeren Anzahl opportunistischer Infektionen und der geringeren Anzahl von GvHD‐Rezidiven.…”

Extracorporeal photopheresis induces NETosis in neutrophils derived from patients with chronic graft‐vs‐host disease

“…According to the reports of different studies, the overall response rates to ECP treatment in steroid refractory GVHD range between 62% to 75% and 31% to 83% for acute and cGVHD, respectively. 1,[4][5][6][7][8][9][10][11][12] Moreover, treatment with ECP has several advantages, as it is not immunosuppressive, it does not blunt the graft vs leukemia effect and there are no significant reported drug interactions with this approach. 13 The exact mechanism of activity of ECP against GVHD is not clear and multiple mechanisms have been suggested.…”

“…Extracorporeal photopheresis (ECP) serves as an efficient second line treatment for both acute and cGVHD. According to the reports of different studies, the overall response rates to ECP treatment in steroid refractory GVHD range between 62% to 75% and 31% to 83% for acute and cGVHD, respectively 1,4‐12 . Moreover, treatment with ECP has several advantages, as it is not immunosuppressive, it does not blunt the graft vs leukemia effect and there are no significant reported drug interactions with this approach 13 .…”