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.

Keywords:

• CAR T-cell therapy
• diffuse large B-cell lymphoma
• relapsed/refractory
• progressive muscular dystrophy
• inherited degenerative disorders

Data Sharing Statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics Approval and Consent to Participate

This study was approved by the Medical Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB20160310). Informed consent was obtained from the patient in strict accordance with the principles of the Declaration of Helsinki. This study is registered at www.chictr.org.cn as ChiCTR-OPN-16008526.

Consent for Publication

Patient consent for publication was obtained.

Acknowledgments

The authors would like to thank all members of the study team, the patient, and his family. We would also like to thank the Bio-Raid Company for the preparation of the CAR T-cells.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests in this work.

Additional information

Funding

This work was supported in part by the National Natural Science Foundation of China (No. 81873444 and No. 82070213 to Yi Xiao and No. 81700160 to Liting Chen) and the Hubei Provincial Science and Technology Key Research Program (No. 2020BCB021).