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Extracorporeal photopheresis as graft-versus-host disease prophylaxis: a randomized controlled trial: Prophylactic extracorporeal photopheresis to prevent graft-versus-host disease
Ali, M. M., Gedde-Dahl, T., Osnes, L. T., Perrier, F., Veierød, M. B., Tjønnfjord, G. E., Iversen, P. O.
Transplantation and cellular therapy. 2023
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Editor's Choice
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for many patients diagnosed with hematological malignancies. A major obstacle is graft-versus-host disease (GvHD) causing significant morbidity and mortality. Extracorporeal photopheresis (ECP) is an increasingly applied GvHD treatment, partly due to its favourable safety profile. In contrast, the use of ECP in preventing GvHD is sparse, and randomized controlled trials (RCTs) are lacking. OBJECTIVE We therefore conducted a RCT to assess if ECP applied post-transplant, could prevent the development of GvHD within the first year of transplantation. STUDY DESIGN We enrolled 157 patients (18-74 years) with a hematological malignancy receiving first allo-HSCT: 76 randomized to the intervention group and 81 to the control group. ECP was initiated directly upon engraftment and was planned twice weekly for two weeks, then once weekly for four weeks. GvHD, relapse, and death were analyzed with Cox regression analysis. RESULTS During the first year, 45 patients in the intervention and 52 control patients developed GvHD (HR=0.82, 95% CI 0.55-1.22, P=0.32). There were no differences in acute or chronic GvHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GvHD between the intervention (per-protocol; n=39 of 76) and the control group (n=77), 46% vs 68%, respectively, (HR 0.47, 95% CI 0.27-0.80, P=0.006). Relapse occurred in 15 patients in the intervention group and in 11 patients among the controls (HR=1.38, 95% CI 0.64-3.01, P=0.42). GvHD-free relapse-free (GRFS) survival, event-free survival, overall survival and non-relapse mortality did not differ significantly between the two study groups. No significant difference in immune reconstitution between the two study groups was revealed. CONCLUSION This first intention-to-treat RCT, investigating ECP as GvHD prophylaxis in allo-HSCT for hematological malignancy does not support the use of ECP as adjunct to standard drug-based GvHD-prophylaxis. This trial was registered at www. CLINICALTRIALS gov as #NCT03204721.
PICO Summary
Population
Adults with a haematological malignancy receiving first allo-HSCT in a single centre in Norway (n=157)
Intervention
Extracorporeal photopheresis (ECP) therapy, 8 sessions over 6 weeks in addition to standard GvHD prophylaxis (n=76)
Comparison
Standard GvHD prophylaxis (n=81)
Outcome
During the first year, 45 patients in the intervention and 52 control patients developed GvHD (HR=0.82, 95% CI 0.55-1.22). There were no differences in acute or chronic GvHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GvHD between the intervention (per-protocol; n=39 of 76) and the control group (n=77), 46% vs 68%, respectively, (HR 0.47, 95% CI 0.27-0.80). Relapse occurred in 15 patients in the intervention group and in 11 patients among the controls (HR=1.38, 95% CI 0.64-3.01). GvHD-free relapse-free (GRFS) survival, event-free survival, overall survival and non-relapse mortality did not differ significantly between the two study groups. No significant difference in immune reconstitution between the two study groups was revealed.
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Randomized phase II trial of extracorporeal phototherapy and steroids vs. steroids alone for newly diagnosed acute GVHD
Mehta, R. S., Bassett, R., Rondon, G., Overman, B. J., Popat, U. R., Hosing, C. M., Rezvani, K., Qazilbash, M. H., Anderlini, P., Jones, R. B., et al
Bone marrow transplantation. 2021
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Editor's Choice
Abstract
Steroids remain the initial therapy for acute graft-vs.-host disease (AGVHD). Strategies to improve response and minimize steroid exposure are needed. We report results of a randomized, adaptive, Bayesian-designed, phase II trial of prednisone with or without extracorporeal photopheresis (ECP) as an initial therapy for patients with newly diagnosed AGVHD. The primary endpoint was success at day 56 defined as: alive, in remission, achieving AGVHD response without additional therapy, and on <1?mg/kg at day 28 and <0.5?mg/kg on day 56 of steroids. Eighty-one patients were randomized to the ECP arm (n?=?51) or steroids alone (n?=?30). Median age was 54 years (range: 17-75); 90% had grade II AGVHD and 10% had grades III and IV AGVHD, with skin (85%), upper (22%)/lower (22%) gastrointestinal, and liver (10%) involvement. The ECP arm had a higher probability of success (0.815) and exceeded the predefined threshold for determining the investigational arm promising. ECP was potentially more beneficial than steroids-alone in skin-only AGVHD (response rate: 72% vs. 57%, respectively) than for visceral-organ AGVHD (47% vs. 43%, respectively). The addition of ECP to steroids may result in higher GVHD response as initial therapy for AGVHD, especially for patients with skin-only involvement.
PICO Summary
Population
Patients with newly-diagnosed acute graft-versus-host disease (AGVHD, n=81)
Intervention
Prednisone with extracorporeal photopheresis (ECP, n=51)
Comparison
Prednisone alone (n=30)
Outcome
The ECP arm had a higher probability of success (0.815) and exceeded the predefined threshold for determining the investigational arm promising. ECP was potentially more beneficial than steroids-alone in skin-only AGVHD (response rate: 72% vs. 57%, respectively) than for visceral-organ AGVHD (47% vs. 43%, respectively).