Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease

Roger Belizaire, Haesook T. Kim, Samuel J. Poryanda, Nikola V. Mirkovic, Evelyn Hipolito, William J. Savage, Carol G. Reynolds, Marie J. Fields, Jennifer Whangbo, Tomohiro Kubo, Sarah Nikiforow, Edwin P. Alyea, Philippe Armand, Corey S. Cutler, Vincent T. Ho, Bruce R. Blazar, Joseph H. Antin, Jerome Ritz, Robert J. Soiffer, John Koreth

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Chronic graft-versus-host disease (cGVHD) affects .50% of hematopoietic stem cell transplant patients. Extracorporeal photopheresis (ECP), an immunomodulatory therapy, provides clinical benefit in steroid-refractory (SR) cGVHD, possibly via regulatory T (Treg) and natural killer (NK) cell expansion. We demonstrated that low-dose interleukin-2 (IL2) led to clinical improvement in SR-cGVHD and stimulated preferential Treg and NK-cell expansion with minimal effect on conventional T (Tcon) cells. We evaluated the effect of ECP (weeks 1-16) plus IL2 (1 3 106 IU/m2, weeks 9-16) in 25 adult patients with SR-cGVHD in a prospective phase 2 trial. Objective responses occurred in 29% and 62% of evaluable patients at weeks 8 (ECP alone) and 16 (ECP plus IL2), respectively. Eight weeks of ECP alone was associated with a marked decline in CD41 Tcon (P 5 .03) and CD81 T cells (P 5 .0002), with minimal change in Treg cells, Treg:Tcon cell ratio, or NK cells. Adding IL2 induced an increase in Treg cells (P, .05 at weeks 9-16 vs week 8), Treg:Tcon cell ratio (P, .0001 at weeks 9-16 vs week 8), and NK cells (P, .05 at weeks 9-16 vs week 8). Patients responding to ECP alone had significantly fewer CD41 Tcon and CD81 T cells at baseline compared with patients who responded after IL2 addition and patients who did not respond; neither Treg nor NK cells were associated with response to ECP alone. Altogether, ECP plus IL2 is safe and effective in patients with SR-cGVHD. ECP and IL2 have distinct immunologic effects, suggesting different therapeutic mechanisms of action. This trial was registered at www.clinicaltrials.gov as #NCT02340676.

Original languageEnglish (US)
Pages (from-to)969-979
Number of pages11
JournalBlood Advances
Volume3
Issue number7
DOIs
StatePublished - Apr 9 2019

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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    Belizaire, R., Kim, H. T., Poryanda, S. J., Mirkovic, N. V., Hipolito, E., Savage, W. J., Reynolds, C. G., Fields, M. J., Whangbo, J., Kubo, T., Nikiforow, S., Alyea, E. P., Armand, P., Cutler, C. S., Ho, V. T., Blazar, B. R., Antin, J. H., Ritz, J., Soiffer, R. J., & Koreth, J. (2019). Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease. Blood Advances, 3(7), 969-979. https://doi.org/10.1182/bloodadvances.2018029124