Histiocyte predominant myocarditis resulting from the addition of interferon gamma to cyclophosphamide-based lymphodepletion for adoptive cellular therapy

Brett A. Schroeder, Ralph Graeme Black, Sydney Spadinger, Shihong Zhang, Karan Kohli, Jianhong Cao, Jose G. Mantilla, Ernest U. Conrad, Stanley R. Riddell, Robin L. Jones, Cassian Yee, Seth M. Pollack*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background Adoptive cellular therapy (ACT) is a promising treatment for synovial sarcoma (SS) with reported response rates of over 50%. However, more work is needed to obtain deeper and more durable responses. SS has a â € cold' tumor immune microenvironment with low levels of major histocompatibility complex (MHC) expression and few T-cell infiltrates, which could represent a barrier toward successful treatment with ACT. We previously demonstrated that both MHC expression and T-cell infiltration can be increased using systemic interferon gamma (IFN-Î 3), which could improve the efficacy of ACT for SS. Case presentation We launched a phase I trial incorporating four weekly doses of IFN-γin an ACT regimen of high-dose cyclophosphamide (HD Cy), NY-ESO-1-specific T cells, and postinfusion low-dose interleukin (IL)-2. Two patients were treated. While one patient had significant tumor regression and resultant clinical benefit, the other patient suffered a fatal histiocytic myocarditis. Therefore, this cohort was terminated for safety concerns. Conclusion We describe a new and serious toxicity of immunotherapy from IFN-γcombined with HD Cy-based lymphodepletion and low-dose IL-2. While IFN-γshould not be used concurrently with HD Cy or with low dose IL-2, IFN-γmay still be important in sensitizing SS for ACT. Future studies should avoid using IFN-γduring the immediate period before/after cell infusion. Trial registration numbers NCT04177021, NCT01957709, and NCT03063632.

Original languageEnglish (US)
Article numbere000247
JournalJournal for immunotherapy of cancer
Volume8
Issue number1
DOIs
StatePublished - Apr 8 2020
Externally publishedYes

Keywords

  • CD8-positive T-lymphocytes
  • immunotherapy, adoptive
  • oncology
  • sarcoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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