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

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 × 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 CD4+ Tcon (P = .03) and CD8+ T cells (P = .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 CD4+ Tcon and CD8+ 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.

• Authors: 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
• Journal: Blood advances (Blood Adv) Vol. 3 Issue 7 Pg. 969-979 (04 09 2019) ISSN: 2473-9537 [Electronic] United States
• PMID: 30936057 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 by The American Society of Hematology.

Chemical References

• Interleukin-2

Topics

• Adult
• Aged
• CD4-Positive T-Lymphocytes
• CD8-Positive T-Lymphocytes
• Cell Proliferation (drug effects, radiation effects)
• Chronic Disease
• Combined Modality Therapy (methods)
• Female
• Graft vs Host Disease (therapy)
• Humans
• Interleukin-2 (immunology, therapeutic use)
• Killer Cells, Natural (cytology)
• Male
• Middle Aged
• Photopheresis (methods)
• T-Lymphocytes, Regulatory (cytology)
• Time Factors
• Treatment Outcome