Clinical efficacy and safety of chimeric antigen receptor T-cell therapy for mantle cell lymphoma with secondary central nervous system involvement

Abstract

Data describing outcomes of chimeric antigen receptor (CAR) T-cell therapy in patients with secondary central nervous system (SCNS) involvement of mantle cell lymphoma (MCL) are limited. We identified 10 patients with MCL and SCNS involvement treated with anti-CD19 CAR T-cell therapy at three US academic centres. Frequent objective responses were observed in the CNS (86%) and systemically (90%), and the 1-year progression-free survival was 47%. Seven patients developed immune-effector-cell-associated-neurotoxicity-syndrome (n = 2 Grade 1, n = 5 Grade 3). Our results suggest that anti-CD19 CAR T-cell therapy in this setting is feasible and additional data regarding neurotoxicity in this population may be warranted.

Keywords: CNS; cellular therapies; non-Hodgkin lymphoma.

Figure 1.. Clinical and Toxicity Courses

A) Clinical courses for all 10 patients, with systemic and CNS-specific disease status shown separately. For the 5 patients who developed disease progression after CAR T-cell therapy, subsequent therapies are as follows: Patient D: radiation therapy to nasopharyngeal mass followed by pirtobrutinib, Patient E: radiation therapy followed by venetoclax, Patient H: whole brain radiation therapy, Patient I: obinutuzumab in combination with lenalidomide, Patient J: palliative radiation therapy to spine. B) Toxicity courses with specific interventions for 5 representative patients who developed neurotoxicity. Patient C and Patient J developed Grade 1 ICANS which resolved without any intervention. Patient D, who had a history of recent seizures in the setting of new CNS disease, developed neurotoxicity symptoms on Day +5. He had increased somnolence and difficulty following commands, which then progressed to intermittent garbled speech and worsening somnolence (electroencephalogram [EEG] was negative). Following treatment with dexamethasone and anakinra, this patient returned to his neurological baseline by Day +8. Patient G developed a new decrement in immune effector cell encephalopathy (ICE) score to 8/10 on Day +6. He was treated with tocilizumab, dexamethasone, and later anakinra, however his ICE scored dropped to 0 on Day +12, prompting transfer to the Neurological ICU. EEG monitoring showed no evidence of seizures. Dexamethasone and anakinra were continued and the patient’s neurological status improved over the course of a week, with transfer out of the Neurological ICU on Day +18. Patient I developed a decrement in mental status with ICE score of 0 on Day +2. EEG showed slowing but no epileptiform activity. Following initiation of dexamethasone, symptoms gradually improved with ICE score 8–9 for several days, until resolution by Day +12.