Coccidioidomycosis, immunoglobulin deficiency: safety challenges with CAR T cells therapy for relapsed lymphoma

Immunotherapy. 2017 Oct;9(13):1061-1066. doi: 10.2217/imt-2017-0070.

Abstract

Treatment of patients with relapsed or refractory lymphoma may require allogenic hematopoietic stem cell transplant (HSCT), but treatment of post-transplant relapse disease remains very challenging. Donor lymphocyte infusion and blinatumomab have been used with limited success for the treatment of relapse. Initial data on donor-derived CAR T cells has shown this modality to be safe and highly effective in various hematological malignancies. We present a case of a patient with highly refractory, transformed follicular lymphoma who failed both autologous and allogenic HSCT. Patient achieved long-lasting complete remission with the use of donor origin CD19 CAR T-cell therapy, without any evidence of graft-versus-host disease flare. Our patient later developed disseminated coccidioidomycosis and persistent hypogammaglobulinemia. Immunotherapy using CD19 CAR T cells can be a highly effective salvage modality, especially in cases of focal lymphoma relapse. Long-term immunosuppression secondary to B cell lymphopenia, hypogammaglobulinemia, immunoglobulin subclass deficiency, fungal infections and other infectious complications need to be monitored and promptly treated as indicated.

Keywords: coccidioidomycosis; donor-derived CAR T cell; immunoglobulin deficiency.

Publication types

  • Case Reports

MeSH terms

  • Agammaglobulinemia / diagnosis*
  • Agammaglobulinemia / therapy
  • Aged
  • Antigens, CD19 / genetics
  • Coccidioides / immunology*
  • Coccidioidomycosis / diagnosis*
  • Coccidioidomycosis / therapy
  • Genetic Engineering
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Male
  • Receptors, Antigen, T-Cell / genetics
  • Recurrence
  • Remission Induction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation

Substances

  • Antigens, CD19
  • Receptors, Antigen, T-Cell