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Not so crystal clear: observations from a case of crystalline arthritis with cytokine release syndrome (CRS) after chimeric antigen receptor (CAR)-T cell therapy

Bone Marrow Transplantation volume 54, pages 632–634 (2019)Cite this article

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As the use of effector T-cell immunotherapy for the treatment of both solid and non-solid malignancy expands, clinicians across all medical specialties are observing an increased incidence of rheumatic and autoimmune complications. Immune-related adverse events (IRAEs) have been well-described with the use of CTLA-4, PD-1, and PDL-1 inhibitors; however, such organ-specific immune-related toxicities have not been widely reported with chimeric antigen receptor (CAR)-T cell therapy. Here, we describe a case of crystalline arthritis observed in the context of cytokine release syndrome (CRS) after CAR-T cell therapy, and we discuss potential mechanistic links.

A 66-year-old man presented with fever and severe bilateral knee pain with functional immobility on day 15 status-post 2nd generation anti-CD19 directed CAR-T cell infusion (dose 2 × 106 cells/kg) for relapsed chronic lymphocytic leukemia (clincaltrials.gov NCT01865617). The CAR-T cells infused into this patient were autologous T cells engineered to express a CD19-targeting CAR comprising an FMC63 scFv, IgG4 hinge spacer, CD28 transmembrane domain, 4-1BB costimulatory domain, and a CD3zeta signaling sequence. The patient denied a history of gout or pseudogout but had recalled prior episodes of bilateral knee swelling. Notable labs and imaging are listed in Table 1. Synovial fluid analysis revealed a sterile inflammatory effusion with both monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals, consistent with a simultaneous gout and pseudogout attack. CAR-T cells were present in the synovial fluid, as measured by flow cytometry. The patient also exhibited features concerning for systemic CRS, such as persistent fevers and hypotension; thus, the patient was treated with one dose of tocilizumab (8 mg/kg IV) and two doses of dexamethasone (10 mg IV), resulting in prompt improvement of arthritis and fevers. Given his rapid improvement, subsequent therapy was narrowed to celecoxib for relief of residual pain.

Table 1 Pertinent laboratory and radiographic features
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Authors and Affiliations

  1. Division of Rheumatology, University of Washington, Seattle, WA, USA

    Sarah H. Chung & Grant Hughes

  2. CLL Society, Claremont, CA, USA

    Brian Koffman

  3. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Cameron J. Turtle, David G. Maloney & Utkarsh H. Acharya

  4. Division of Medical Oncology, University of Washington, Seattle, WA, USA

    Cameron J. Turtle, David G. Maloney & Utkarsh H. Acharya

  5. Division of Cellular Therapy in Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA

    Utkarsh H. Acharya

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  1. Sarah H. Chung
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  2. Grant Hughes
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  6. Utkarsh H. Acharya
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Correspondence to Sarah H. Chung.

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Chung, S.H., Hughes, G., Koffman, B. et al. Not so crystal clear: observations from a case of crystalline arthritis with cytokine release syndrome (CRS) after chimeric antigen receptor (CAR)-T cell therapy. Bone Marrow Transplant 54, 632–634 (2019). https://doi.org/10.1038/s41409-018-0357-4

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