Organ-specific response after low-dose interleukin-2 therapy for steroid-refractory chronic graft-versus-host disease.

Abstract

Despite new therapeutic options, treatment of steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains challenging as organ involvement and clinical manifestations are highly variable. In previous trials of low-dose interleukin-2 (LD IL-2), we established the safety and efficacy of LD IL-2 for the treatment of SR-cGVHD. In the present report, we combined five phase 1 or 2 clinical trials conducted at our center to investigate organ-specific response rate, coinvolvement of organs, predictors of organ-specific response, and its possible association with immune response. For the 105 adult patients included in this report, the overall response rate after 8 or 12 weeks of LD IL-2 was 48.6% and 53.3%, including late responses in patients who continued treatment for extended periods. Skin was the most frequent organ involved (84%). The organ-specific response rate was highest in liver (66.7%) followed by the gastrointestinal tract (62.5%), skin (36.4%), joint/muscle/fascia (34.2%), and lung (19.2%). In multivariable analysis, shorter time from diagnosis of cGVHD to IL-2 initiation, shorter time from transplant to IL-2 initiation, and fewer prior therapies were associated with overall response as well as skin response. For immunologic correlates, the ratio of regulatory T cells:conventional T cells (ie, CD4Treg:CD4Tcon) ratio at 1 week was significantly higher in patients with overall and skin response; skin response was significantly associated with lower number of total CD3 T cells, CD4Tcon cells, and CD8 T cells and a higher number of B cells. For lung responders, terminal effector memory cell counts were lower within all T-cell populations compared with nonresponders. Organ-specific mechanisms of injury should be investigated, and organ-specific targeted therapies need to be developed.

• Authors: Haesook T Kim, John Koreth, Jennifer Whangbo, Sarah Nikiforow, Carol G Reynolds, Peter Stowe, Vincent T Ho, Corey Cutler, Joseph H Antin, Robert J Soiffer, Jerome Ritz
• Journal: Blood advances (Blood Adv) Vol. 6 Issue 15 Pg. 4392-4402 (08 09 2022) ISSN: 2473-9537 [Electronic] United States
• PMID: 35617682 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• Interleukin-2
• Steroids

Topics

• Adult
• CD8-Positive T-Lymphocytes
• Graft vs Host Disease (drug therapy, etiology)
• Humans
• Interleukin-2 (therapeutic use)
• Steroids (therapeutic use)
• T-Lymphocytes, Regulatory