Recapitulated Late-Onset Inflammatory Toxicities and Progressive Dysautonomia with Persistence of Central Memory CD4+ Chimeric Antigen Receptor T Cells in a Case of Transformed Follicular Lymphoma: Case Report.

Abstract

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has been widely used and is highly effective for B-cell lymphoid malignancies. Immune-mediated adverse effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in the acute phase and are monophasic after CAR T-cell therapy. However, late-onset inflammatory and neurological toxicities have not been well studied. We encountered a patient with recurrent late-onset inflammatory toxicities and progressive dysautonomia after CD19-directed CAR T-cell therapy. A 69-year-old man was treated with CD19-directed CAR T-cell therapy for transformed follicular lymphoma. Triphasic inflammation with stomatitis, cytopenia, and noninfectious pneumonia was first observed 7 months after CAR T-cell infusion. Progressive dysautonomia was also observed and eventually fatal. Residual CAR T cells, predominantly central memory CD4+ cells, were detectable in peripheral blood approximately 1 year after CAR T-cell infusion. The cytokine profile with the lack of tumor necrosis factor-α, interferon-γ, and interleukin-1β elevation in the peripheral blood and cerebrospinal fluid was inconsistent with that of typical CRS or ICANS. The persistence of central memory CD4+ CAR T cells might be associated with unique manifestations of late-onset immune-mediated adverse effects. More cases should be accumulated to elucidate the mechanism and establish the optimal management strategy of late-onset immune-mediated toxicities previously unrecognized.

• Authors: Mitsutaka Nishimoto, Teruhito Takakuwa, Masatomo Kuno, Yosuke Makuuchi, Hiroshi Okamura, Yasuhiro Nakashima, Hideo Koh, Hiroto Namba, Yoshiaki Itoh, Masayuki Hino, Hirohisa Nakamae
• Journal: Acta haematologica (Acta Haematol) Vol. 146 Issue 4 Pg. 338-342 ( 2023) ISSN: 1421-9662 [Electronic] Switzerland
• PMID: 37088083 (Publication Type: Case Reports)
• Copyright: © 2023 S. Karger AG, Basel.

Chemical References

• cell-associated neurotoxicity
• Receptors, Chimeric Antigen
• Antigens, CD19

Topics

• Male
• Humans
• Aged
• Receptors, Chimeric Antigen
• Lymphoma, Follicular
• Neoplasm Recurrence, Local
• Immunotherapy, Adoptive (adverse effects)
• Lymphoma, Non-Hodgkin
• CD4-Positive T-Lymphocytes
• Antigens, CD19