CAR T-Cell Therapy Shown Safe, Effective in MCL With CNS Involvement

A small study suggests the use of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with mantle cell lymphoma (MCL) with secondary central nervous system (SCNS) involvement is feasible, but additional research on neurotoxicity is needed. The findings were published in the British Journal of Haematology.¹

While CAR T-cell therapies have changed the treatment landscape for patients with hematological malignancies, data on the outcomes of CAR T-cell therapy among patients with MCL and CNS metastases are limited. The study authors noted prior research demonstrating a prognosis of less than 5 months in these rare cases. Historically, ibrutinib has shown improved overall survival (OS) vs chemoimmunotherapy in patients with MCL and SCNS involvement, but data on novel or alternative therapies are still lacking.

The new study aimed to gain insight into the efficacy and safety of CAR T-cell therapy in this patient population through a retrospective, multicenter analysis.

Researchers identified 10 patients with MCL and a history of SCNS involvement who were treated with anti-CD19 CAR T-cell therapy at 3 academic centers in the United States. Patient data were collected from electronic medical records and included patient demographics, disease characteristics, prior lines of therapy, the onset and duration of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), available scans, cerebral spinal fluid (CSF) testing results, disease progression, and survival status. 

Most patients received brexucabtagene autoleucel (brexu-cel), except 1 who received tisagenlecleucel. The median age at the start of therapy was 60 years, and patients had a median of 4 prior lines of therapy. Most patients (90%) experienced disease progression within 24 months of diagnosis, and 7 patients had active CNS disease based on imaging or CSF results at the time of CAR T-cell infusion. The other 3 patients had confirmed CNS disease 2 months, 5 months, and 18 months before CAR T-cell therapy.

Nine patients showed complete response (CR) with respect to systemic disease at 30 days as determined by PET/CT scans, and 1 patient’s disease progressed. Six of the 7 patients with active CNS disease (86%) achieved an objective response within 30 days of infusion. Of these patients, 2 had a CNS CR, 4 showed a CNS partial response, and 1 had stable CNS disease.

At a median follow-up of 15.4 months for survivors, 7 patients were alive, 5 of whom were in remission. Three patients were deceased due to disease progression, 2 of whom had systemic disease progression only and 1 who had both systemic and CNS disease progression. Overall, the median progression-free survival (PFS) was 11.7 months, and median OS was not reached. The 12-month OS was 79% (95% CI, 38%-94%) and 12-month PFS was 47% (95% CI, 15%-74%) in the overall cohort. Among those with active CNS disease at the time of infusion, median OS was not reached and median PFS was 11.7 months (95% CI, 0.6-NR). In this subgroup, the PFS at 12 months was 36% (95% CI, 5%-70), and OS at 12 months was 71% (95% CI, 26%-92%).

While 9 patients out of 10 experienced CRS and 7 developed ICANS, both known risks of CAR T-cell therapy, there was no treatment-related mortality in the cohort, and all cases of neurotoxicity were reversible. The maximum grade of CRS was 1, 2, and 3 in 5 patients, 3 patients, and 1 patient, respectively, and the median onset was 4 days (range, 1-14). The median CRS duration was 5 days (range, 2-9). Regarding ICANS, 2 patients had grade 1 and 5 patients had grade 3 ICANS with a median time to onset of 6 days (range, 2-11). The median duration was 11 days (range, 4-23).

The analysis was limited by a small sample size and its retrospective nature, but the authors note that the study provides additional data on a rare patient population that warrants further study. They added that the ongoing TRANSCEND NHL 001 trial of lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas notably includes patients with CNS,² and the results will provide more data to consider when choosing a CAR T-cell therapy to treat this patient population.

“The results from our cohort of 10 patients with MCL and SCNS disease demonstrate that anti-CD19 CAR T-cell therapy in this population is feasible and efficacious,” the authors concluded. “As in the recent US Lymphoma CAR T Consortium retrospective study of brexu-cel,³ we found that CAR T-cell therapy was effective in heavily pre-treated, refractory patients.”

References

1. Ryan CE, Zon RL, Redd R, et al. Clinical efficacy and safety of chimeric antigen receptor T-cell therapy for mantle cell lymphoma with secondary central nervous system involvement. Br J Haematol. Published online August 16, 2023. doi:10.1111/bjh.19037

2.Study evaluating the safety and pharmacokinetics of JCAR017 in B-cell non-Hodgkin lymphoma (TRANSCEND-NHL-001). ClinicalTrials.gov. Updated March 3, 2023. Accessed August 18, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT02631044

3. Wang Y, Jain P, Locke FL, Maurer MJ, Frank MJ, Munoz JL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023;41(14):2594-2606. doi:10.1200/JCO.22.01797