Background: CAR-T therapy is a crucial method for treating relapsed/refractory acute B-lymphoblastic leukemia (ALL). Elderly patients often have poor treatment tolerance and limited treatment options.

Objective: To observe the efficacy of sequential CAR-T therapy combined with demethylating agents and personalized targeted drugs in elderly patients with relapsed/refractory acute B-lymphoblastic leukemia (B-ALL).

Methods: This study included data from 18 patients treated at Beijing Boren Hospital between June 2018 and March 2023, with follow-up until June 20, 2024. All patients were over 50 years old, diagnosed with relapsed/refractory acute B-ALL. All patients relapsed after chemotherapy or allo-HSCT and received two different antigen-targeted sequential CAR-T therapies, followed by maintenance therapy with BCL2 inhibitors, demethylating agents, and specific targeted drugs. The cohort consisted of 5 males and 13 females, with an age range of 53 to 74 years (median age: 60.5 years). Four patients (22.2%) were Ph+, one patient (5.56%) had undergone allo-HSCT before CAR-T therapy, and four patients (22.2%) underwent allo-HSCT after CAR-T therapy.

Results: All 18 elderly patients achieved MRD-negative remission by flow cytometry after the first CAR-T therapy and then received a second sequential CAR-T therapy targeting different antigens. One-year continuous remission was achieved in 12 patients (66.7%), and two-year continuous remission in 6 patients (33.3%). Progression-free survival (PFS) after sequential CAR-T therapy ranged from 2 months to 39 months (as of June 20, 2024). The two-year event-free survival (EFS) rate was 65.81% (95% CI: 39.06%~83.01%), and the three-year EFS rate was 29.25% (95% CI: 7.7%~55.34%), with a median EFS of 849 days. The two-year overall survival (OS) rate was 79.91% (95% CI: 49.31%~93.13%), and the three-year OS rate was 59.94% (95% CI: 27.34%~81.7%), with the median OS not reached. During the first CAR-T therapy, the probability of CRS was 66.7%, with 11 patients (61.1%) experiencing grade 1 CRS, 1 patient (5.6%) experiencing grade 2 CRS, and no patients experiencing grade 3 or higher CRS or ICANS. Only one patient experienced grade 1 CRS during the second CAR-T therapy.

Conclusion:

  1. CAR-T therapy in elderly patients with relapsed/refractory B-ALL shows high remission rates, minimal side effects, and high safety, effectively prolonging disease-free survival and overall survival.

  2. For elderly patients with relapsed/refractory B-ALL, sequential CAR-T therapy combined with BCL2 inhibitors and demethylating agents (decitabine or azacitidine) as part of maintenance therapy can effectively extend remission duration, providing a new treatment option for these patients.

Disclosures

No relevant conflicts of interest to declare.

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2024
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