Safety of CAR T-Cell Therapy in Patients with Active Autoimmune Diseases: A Case Report
Alec Friedman1, Andrew Lipsky2, Christian Gordillo3, Ran Reshef3, Sarah Wesley1
1Neurology, Columbia University College of Physicians and Surgeons, 2Medical Hematology & Oncology, 3Blood and Marrow Transplantation and Cell Therapy Program, Columbia University Irving Medical Center
Objective:
Describe the case of a patient with diffuse large B-cell lymphoma (DLBCL) with active paraneoplastic neuropathy at the time of chimeric antigen receptor therapy (CAR-T) who improved.
Background:
CAR-T is now a well-established treatment for several cancers. However, the use of CAR-T is limited by immune-related adverse events (irAEs). It is unknown whether immune dysregulation disorders might increase the risk for irAEs, and whether successful use of CAR-T might ameliorate a concurrent paraneoplastic syndrome.
Design/Methods:
N/A
Results:

A 72-year-old woman with DLBCL treated with six cycles of R-CHOP, as well as two doses of intrathecal methotrexate, presented with progressive limb weakness and numbness over several weeks. Examination revealed 3/5 intrinsic hand muscles, 4/5 bilateral hip flexors, 2/5 left foot plantar/dorsiflexion, 1/5 in the right foot and absent patellar/Achilles reflexes bilaterally. Sensation was decreased to all modalities below the ankles.

 

EMG/NCS demonstrated severe symmetrical sensorimotor demyelinating polyneuropathy with active and chronic denervation. She received 2g/kg IVIG with limited benefit. She was refractory to additional MATRix chemotherapy. Ultimately, she proceeded with lisocabtagene maraleucel (liso-cel) CAR-T.

 

She had CRS grade 1 (fever) treated with tocilizumab and dexamethasone. She had a single drop in her ICE score to 9/10, but this resolved. She was safely discharged on post-infusion Day 8.

 

Examination was improved three months later with 4+/5 hip flexion, 4-5/5 dorsiflexion and plantarflexion bilaterally, normal patellar reflexes, absent ankle jerk. She could mobilize independently. She had no evidence of disease on PET/CT until a recurrence 8 months later successfully treated with rituximab, lenalidomide, and zanubrutinib.

Conclusions:
We hope that our experience might open the discussion for broader use of CAR-T in oncology patients with autoimmune and paraneoplastic syndromes.
10.1212/WNL.0000000000204493