RT Journal Article
SR Electronic
T1 Histiocyte predominant myocarditis resulting from the addition of interferon gamma to cyclophosphamide-based lymphodepletion for adoptive cellular therapy
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e000247
DO 10.1136/jitc-2019-000247
VO 8
IS 1
A1 Brett A Schroeder
A1 Ralph Graeme Black
A1 Sydney Spadinger
A1 Shihong Zhang
A1 Karan Kohli
A1 Jianhong Cao
A1 Jose G Mantilla
A1 Ernest U Conrad
A1 Stanley R Riddell
A1 Robin L Jones
A1 Cassian Yee
A1 Seth M Pollack
YR 2020
UL http://jitc.bmj.com/content/8/1/e000247.abstract
AB 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 ‘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-γ), which could improve the efficacy of ACT for SS.Case presentation We launched a phase I trial incorporating four weekly doses of IFN-γ in 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-γ combined with HD Cy-based lymphodepletion and low-dose IL-2. While IFN-γ should not be used concurrently with HD Cy or with low dose IL-2, IFN-γ may still be important in sensitizing SS for ACT. Future studies should avoid using IFN-γ during the immediate period before/after cell infusion.Trial registration numbers NCT04177021, NCT01957709, and NCT03063632.