Utilizing BTK Inhibitors for Maintenance and Long-Term Control Following CAR-T Cell Therapy in B-Cell Non-Hodgkin Lymphoma

Background:

Following chimeric antigen receptor (CAR)-T cell therapy, achieving long-term durability in approximately 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) cases remains a significant challenge. There is ongoing consideration that BTK inhibitors may serve as a potential option for maintenance therapy in these patients.

Methods:

A retrospective analysis was conducted on patients who were evaluated as remission (complete remission or partial remission) 3 months after CD19-CAR-T treatment, and were treated with BTKi maintenance therapy to observe the progression-free survival and overall survival of the patients.

Results:

From December 2019 to March 2024, a total of 37 patients were included in the study, with diagnoses comprising CNS lymphoma (14/37), CLL/Richter (5/37), MCL (2/37), DLBCL (14/37), and tFL (3/37). Of these patients, 43% (16/37) were male, with a median age of 52 years (range 21-74). Among them, 23 patients received zanubrutinib, while 14 received either Orelabrutinib or ibrutinib. NGS testing was conducted in 24 patients, revealing MYD88 and/or CD79B mutations in 8/24 cases. Median maintenance duration was 510 days (range 90-1370). Median follow-up time was 30.61 months, with only 2 patients experiencing relapse and 3 deaths recorded. Median progression-free survival (PFS) and overall survival (OS) were not reached. Comparing patients with and without MYD88/CD79B mutations, the 3-year PFS rates were 85.7% vs. 70% (p=0.375). Patients eligible for BTK inhibitors (CNS involvement, chronic lymphocytic leukemia, mantle cell lymphoma) compared to others(DLBCL and tFL) had 3-year PFS rates of 78.3% and 90% (p=0.230), respectively.

Conclusion:

BTK inhibitors could serve as maintenance therapy for patients achieving remission with B-NHL CAR-T within three months, with potentially greater benefits observed in those with the MCD genetic subtype.

No relevant conflicts of interest to declare.