苯达莫司汀淋巴细胞清除后使用阿基仑赛是安全的，并与炎症细胞因子减少相关

Lymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy of bendamustine (Benda) to standard fludarabine/cyclophosphamide (Flu/Cy) LD before CD19-directed, CD28-costimulated CART axicabtagene ciloleucel (axi-cel) for patients with large B-cell lymphoma (LBCL) and follicular lymphoma (FL).

We analyzed 59 patients diagnosed with LBCL (n = 48) and FL (n = 11) consecutively treated with axi-cel at the University of Pennsylvania.

We also analyzed serum samples for cytokine levels and metabolomic changes before and after LD. Flu/Cy and Benda demonstrated similar efficacy, with complete remission rates of 51. 4% and 50. 0% (P = . 981), respectively, and similar progression-free and overall survivals. Any-grade cytokine-release syndrome occurred in 91. 9% of patients receiving Flu/Cy vs 72. 7% of patients receiving Benda (P = . 048); any-grade neurotoxicity after Flu/Cy occurred in 45. 9% of patients and after Benda in 18. 2% of patients (P = . 031).

In addition, Flu/Cy was associated with a higher incidence of grade ≥3 neutropenia (100% vs 54. 5%; P < . 001), infections (78. 4% vs 27. 3%; P < . 001), and neutropenic fever (78. 4% vs 13. 6%; P < . 001). These results were confirmed both in patients with LBCL and those with FL.

Mechanistically, patients with Flu/Cy had a greater increase in inflammatory cytokines associated with neurotoxicity and reduced levels of metabolites critical for redox balance and biosynthesis.

This study suggests that Benda LD may be a safe alternative to Flu/Cy for CD28-based CART CD19-directed immunotherapy with similar efficacy and reduced toxicities. Benda is associated with reduced levels of inflammatory cytokines and increased anabolic metabolites.