CAR T-Cell Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma with Progressive Muscular Dystrophy: A Case Report

Abstract

Muscular dystrophies are a heterogeneous group of genetically inherited degenerative disorders defined by dystrophic features on pathological assessment of muscle biopsy specimens. Muscular dystrophies and lymphoma are not common concomitant diseases. Chimeric antigen receptor (CAR) T-cell immunotherapy for lymphoma patients with inherited degenerative diseases, such as muscular dystrophies, has not been previously reported. We report a relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patient with progressive muscular dystrophy (PMD) characterized by progressive muscle weakness that affected the limb, axial and facial muscles. He was identified to be a germline DYSF p.R204* homozygous mutation carrier. The patient received a murine monoclonal anti-CD19 and anti-CD22 CAR T-cell “cocktail” and suffered from a mild case of grade 1 cytokine release syndrome (CRS). One month after the CAR T-cell infusion, he achieved complete remission of his lymphoma without minimal residual disease (MRD), as assessed by radiography. One year after the infusion, the Deauville score was stable at 1. Currently, patient has been in remission for over three years after receiving anti-CD19 and anti-CD22 CAR T-cell therapy. This case provides evidence for the use of CAR T-cell therapy in lymphoma patients with inherited degenerative disorders. Achieving remission of the lymphoma and subsequent administration of γ-globulin as well as zoledronic acid reduced the muscular dystrophy symptoms.