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Randomized phase II trial of extracorporeal phototherapy and steroids vs. steroids alone for newly diagnosed acute GVHD

Bone Marrow Transplantation volume 56, pages 1316–1324 (2021)Cite this article

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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.

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Fig. 1: Patient consort diagram.
Fig. 2: Non-relapse mortality by success or failure.
Fig. 3: Adverse events.
Fig. 4: Days 28 and 56 steroid doses by treatment arm.
Fig. 5: Long-term outcomes.

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Acknowledgements

This physician-initiated trial was supported by a grant from Therakos, Inc., a Mallinckrodt Pharmaceuticals company. Additional support was provided through the Cancer Center Support Grant (NCI Grant P30 CA016672).

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Authors and Affiliations

  1. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas Cancer Center, Houston, TX, USA

    Rohtesh S. Mehta, Gabriela Rondon, Bethany J. Overman, Uday R. Popat, Chitra M. Hosing, Katy Rezvani, Muzaffar H. Qazilbash, Paolo Anderlini, Roy B. Jones, Partow Kebriaei, David Marin, Issa F. Khouri, Betul Oran, Stefan O. Ciurea, Kayo Kondo, Elizabeth J. Shpall, Richard E. Champlin & Amin M. Alousi

  2. Department of Biostatistics, The University of Texas Cancer Center, Houston, TX, USA

    Roland Bassett

  3. Huntsman Cancer Center, University of Utah, Salt Lake City, UT, USA

    Daniel R. Couriel

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  1. Rohtesh S. Mehta
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Contributions

RSM contributed patient enrollment, paper writing, and interpretation of results; RB contributed to trial design, interpretation of results, and statistical analysis; GR contributed data collection and interpretation of results; BJO contributed data collection; URP, CMH, MQ, PA, IFK, BO, SOC, and EJS contributed patient enrollment and interpretation of results; KR contributed patient enrollment, laboratory analysis, and interpretation of results; DM and KK contributed laboratory analysis and interpretation of results; DRC contributed study design; REC contributed to study design, patient enrollment, and interpretation of results; and AMA contributed to study design, enrollment of patients on study, interpretation of results, and wrote the paper. All authors reviewed and approved the paper.

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Correspondence to Amin M. Alousi.

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AMA has served as a speaker for Therakos, Inc. Other authors declare no conflict of interest.

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Mehta, R.S., Bassett, R., Rondon, G. et al. Randomized phase II trial of extracorporeal phototherapy and steroids vs. steroids alone for newly diagnosed acute GVHD. Bone Marrow Transplant 56, 1316–1324 (2021). https://doi.org/10.1038/s41409-020-01188-4

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