Extracorporeal photopheresis as second-line treatment for acute graft-versus-host disease: impact on six-month freedom from treatment failure

Abstract

Second-line therapy for corticosteroid-refractory or -dependent acute graft-versus-host disease remains ill-defined, due to limited efficacy of drugs and evolving clinical trial endpoints. Six-month freedom from treatment failure has been proposed as a novel clinical trial endpoint and is defined by the absence of death, malignancy relapse/progression, or addition of a next line of systemic immunosuppressive therapy within 6 months of intervention and prior to diagnosis of chronic graft-versus-host disease. We analyzed the 6-month freedom from treatment failure endpoint in 128 patients enrolled from three centers who were treated with extracorporeal photopheresis as second-line therapy for acute graft-versus-host disease. The incidence of 6-month freedom from treatment failure was 77.3% with a 2-year survival rate of 56%. Corticosteroid dose or response status at onset of second-line therapy did not influence outcome. Higher grade of acute graft-versus-host disease (grade 2 versus grades 3-4) at onset of photopheresis predicted for poor outcome as measured by survival (hazard ratio 2.78, P<0.001), non-relapse mortality (hazard ratio 2.78, P=0.001) and 6-month freedom from treatment failure (hazard ratio 3.05, P<0.001). For the 91 patients who achieved 6-month freedom from treatment failure, 1-year, 2-year and 3-year survival rates were 78.9%, 70.8% and 69.5%, respectively. Six-month freedom from treatment failure is a reasonable early surrogate for outcome and should be considered as a clinical trial endpoint. This study demonstrates the durable effect of photopheresis as second-line therapy for corticosteroid-refractory or -dependent acute graft-versus-host disease using 6-month freedom from treatment failure as the primary endpoint.

Extracorporeal photopheresis in the treatment of acute graft‐versus‐host disease: a single‐center experience

“…The CR rate in our study (48%) was somewhat lower than that in some of the previous publications with adult patients (52%‐91%) but in line with some other reports, such as that by Perfetti and colleagues (52%) and Hautmann and colleagues (30%). A total of 62% of the present patients showed some response to ECP, and in the second‐line treatment the ORR was 71%, while the CR rate was 56%.…”

“…A total of 62% of the present patients showed some response to ECP, and in the second‐line treatment the ORR was 71%, while the CR rate was 56%. In the largest study with 128 adult patients with steroid‐refractory or steroid‐dependent aGVHD, the ORR of ECP as the second‐line treatment was 77% and the CR rate was 67%. However, in the study by Das‐Gupta and colleagues, the proportion of the patients with Grade III or IV aGVHD was lower than that in this study (30% vs. 81%, respectively).…”

“…In the largest study with 128 adult patients with steroid‐refractory or steroid‐dependent aGVHD, the ORR of ECP as the second‐line treatment was 77% and the CR rate was 67%. However, in the study by Das‐Gupta and colleagues, the proportion of the patients with Grade III or IV aGVHD was lower than that in this study (30% vs. 81%, respectively). In our patient population, in line with previous reports, the skin involvement presented the most favorable target (CR, 77%), whereas only one‐third of our patients with gut or liver involvement showed CR.…”

“…The knowledge of the efficacy of ECP in aGVHD is increasing but the numbers of patients in most publications have remained small. Five large studies with 128, 72, 59, 57, and 50 patients have been published . Two of them have included only children .…”

Extracorporeal photopheresis for treatment of adults and children with acute GVHD: UK consensus statement and review of published literature

“…20,21 A more recent larger multicenter series documented the outcome of 139 patients treated with ECP as second-line therapy for steroid-refractory and -dependent GVHD. 25 Grade III and IV Use of ECP in aGVHD E Das-Gupta et al aGVHD was present at the onset of ECP in 39 patients (35%) with stages 3 and 4, cutaneous in 29 (21%), GI in 57 (41%) and hepatic in 25 (18%). The median number of ECP treatments was 11 (range 2-42); 77% patients responded to ECP.…”