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

AI Article Synopsis

  • Treating steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains difficult despite new therapies, but low-dose interleukin-2 (LD IL-2) has shown promise in clinical trials conducted at a specific center.
  • In a study involving 105 adult patients, the overall response rate to LD IL-2 treatment was around 48.6% to 53.3%, with skin being the most commonly affected organ (84%) and the liver showing the highest organ-specific response rate (66.7%).
  • Factors like quicker initiation of IL-2 treatment after diagnosis, fewer previous treatments, and specific immune system ratios were linked to better responses, suggesting a need for further research on organ-specific

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636330PMC
http://dx.doi.org/10.1182/bloodadvances.2022007773DOI Listing

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