苯达莫司琼淋巴清除术是用于治疗侵袭性B细胞淋巴瘤的阿西卡布塔吉环素白细胞介素治疗的耐受性良好的选择性替代方案,与氟达拉滨和环磷酰胺淋巴清除术相比。
Bendamustine lymphodepletion is a well-tolerated alternative to fludarabine and cyclophosphamide lymphodepletion for axicabtagene ciloleucel therapy for aggressive B-cell lymphoma.
发表日期:2023 Sep 05
作者:
Shin Yeu Ong, Stacy Pak, Matthew Mei, Yan Wang, Leslie Popplewell, John H Baird, Alex F Herrera, Geoffrey Shouse, Liana Nikolaenko, Jasmine Zain, James Godfrey, Myo Htut, Ahmed Aribi, Ricardo Spielberger, Joshua Mansour, Stephen J Forman, Joycelynne Palmer, Lihua E Budde
来源:
AMERICAN JOURNAL OF HEMATOLOGY
摘要:
氟达拉滨/环磷酰胺(Flu/Cy)在淋巴瘤标准护理策略前的淋巴消融(LD)中得到证实。目前需要测试替代的LD方案以保证疗效、提高安全性,并应对最近的全国性氟达拉滨药品短缺的挑战。我们回顾性评估了在我院接受本达特替丁(n = 27)或Flu/Cy(n = 42)前辅助生长率控制抗原T细胞治疗axicabtagene ciloleucel(axi-cel)的复发/难治性侵袭性B细胞淋巴瘤患者的结果。从术前LD到axi-cel输注时,本达特替丁组绝对淋巴细胞计数的中位数变化为-0.6×109 /L,而Flu/Cy组的中位数变化为-0.7×109 /L。本达特替丁组的全局最佳反应率/完全缓解率为77.8%(95% CI:57.7%-91.4%)/48.1%(95% CI:28.7%-68.1%),而Flu/Cy组的全局最佳反应率/完全缓解率为81.0%(95% CI:65.9%-91.4%)/50.0%(95% CI:34.2%-65.8%)。本达特替丁组的6个月无进展生存率为43.8%(95% CI:24.7%-61.3%),Flu/Cy组为55.6%(95% CI:39.0%-69.3%);而6个月总体生存率分别为81.5%(95% CI:61.1%-91.8%)和90.4%(95% CI:76.4%-96.3%)。在根据基线先前治疗次数和难治性疾病进行调整后,与Flu/Cy治疗的患者相比,本达特替丁治疗的患者在经历进展/复发/死亡的风险上没有显示出增加的危险性(aHR:1.4 [95% CI:0.7-2.8];p = .32),死亡的风险也没有增加(aHR:1.6 [95% CI:0.5-5.6];p = .46)。在本达特替丁组和Flu/Cy组中,任何级别/≥3级CRS的观察情况分别为89%/3.7%和86%/4.8%,而任何级别的ICANS和≥3级ICANS的观察情况分别为30%/19%和55%/31%。虽然相对于本达特替丁治疗的患者,更多的Flu/Cy治疗的患者经历了≥3级中性粒细胞减少(100% vs 68%),但≥3级感染并发症相当(24% vs 19%)。与Flu/Cy组相比,有更多的患者在门诊接受了本达特替丁辅助生长率控制抗原T细胞治疗和axi-cel,而没有增加毒性,并且住院时间中位数更短。总之,我们观察到在接受axi-cel之前接受本达特替丁辅助生长率控制抗原T细胞治疗的患者在疗效方面与接受Flu/Cy的患者相当,并且在任何级别ICANS方面较低。© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
Fludarabine/cyclophosphamide (Flu/Cy) is established for lymphodepletion (LD) prior to standard-of-care CAR T-cell therapy for lymphoma. There is ongoing need to test alternative LD regimens to preserve efficacy, improve safety, and address challenges including the recent national fludarabine shortage. We retrospectively evaluated outcomes among patients with relapsed/refractory aggressive B-cell lymphoma who received bendamustine (n = 27) or Flu/Cy (n = 42) LD before axicabtagene ciloleucel (axi-cel) at our institution. The median change in absolute lymphocyte count from pre-LD to time of axi-cel infusion was -0.6×109 /L in bendamustine cohort and -0.7×109 /L in Flu/Cy cohort. The best overall response/complete response rates were 77.8% (95% CI: 57.7%-91.4%)/48.1% (95% CI: 28.7%-68.1%) among bendamustine cohort and 81.0% (95% CI: 65.9%-91.4%)/50.0% (95% CI: 34.2%-65.8%) among Flu/Cy cohort. Six-month progression-free survival were 43.8% (95% CI: 24.7%-61.3%) and 55.6% (95% CI: 39.0%-69.3%) in bendamustine and Flu/Cy cohorts, while 6-month overall survival were 81.5% (95% CI: 61.1%-91.8%) and 90.4% (95% CI: 76.4%-96.3%), respectively. Relative to Flu/Cy-treated patients, bendamustine-treated patients did not show an increase in hazards associated with experiencing progression/relapse/death (aHR:1.4 [95% CI: 0.7-2.8]; p = .32) or death (aHR:1.6 [95% CI: 0.5-5.6]; p = .46), after adjusting for baseline number of prior therapies and refractory disease. Any grade/grade ≥3 CRS were observed in 89%/3.7% and 86%/4.8% among bendamustine and Flu/Cy cohorts, while any grade ICANS/grade ≥3 ICANS were observed in 30%/19% and 55%/31% respectively. While more Flu/Cy-treated patients experienced grade ≥3 neutropenia compared with bendamustine-treated patients (100% vs. 68%), grade ≥3 infectious complications were comparable (24% vs. 19% respectively). More patients received bendamustine LD and axi-cel as outpatient than Flu/Cy cohort, without increased toxicities and with shorter median inpatient stays. In conclusion, we observed comparable efficacy and lower any grade ICANS among patients receiving bendamustine relative to Flu/Cy LD, followed by axi-cel.© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.