Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain.
Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
J Clin Oncol. 2024 Jan 10;42(2):205-217. doi: 10.1200/JCO.23.01097. Epub 2023 Oct 24.
Approximately 30%-40% of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) infused with CD19-targeted chimeric antigen receptor (CAR) T cells achieve durable responses. Consensus guidelines suggest avoiding bendamustine before apheresis, but specific data in this setting are lacking. We report distinct outcomes after CAR T-cell therapy according to previous bendamustine exposure.
The study included CAR T-cell recipients from seven European sites. Safety, efficacy, and CAR T-cell expansion kinetics were analyzed according to preapheresis bendamustine exposure. Additional studies on the impact of the washout period and bendamustine dose were performed. Inverse probability treatment weighting (IPTW) and propensity score matching (PSM) analyses were carried out for all efficacy comparisons between bendamustine-exposed and bendamustine-naïve patients.
The study included 439 patients with R/R LBCL infused with CD19-targeted commercial CAR T cells, of whom 80 had received bendamustine before apheresis. Exposed patients had significantly lower CD3 cells and platelets at apheresis. These patients had a lower overall response rate (ORR, 53% 72%; < .01), a shorter progression-free survival (PFS, 3.1 6.2 months; = .04), and overall survival (OS, 10.3 23.5 months; = .01) in comparison with the bendamustine-naïve group. Following adjustment methods for baseline variables, these differences were mitigated. Focusing on the impact of bendamustine washout before apheresis, those with recent (<9 months) exposure (N = 42) displayed a lower ORR (40% 72%; < .01), shorter PFS (1.3 6.2 months; < .01), and OS (4.6 23.5 months; < .01) in comparison with bendamustine-naïve patients. These differences remained significant after IPTW and PSM analysis. Conversely, the cumulative dose of bendamustine before apheresis did not affect CAR-T efficacy outcomes.
Recent bendamustine exposure before apheresis was associated with negative treatment outcomes after CD19-targeted CAR T-cell therapy and should be therefore avoided in CAR T-cell candidates.
约 30%-40%接受 CD19 靶向嵌合抗原受体（CAR）T 细胞输注的复发性/难治性（R/R）大 B 细胞淋巴瘤（LBCL）患者可获得持久缓解。共识指南建议在单采术前行避免使用苯达莫司汀，但在这种情况下缺乏具体数据。我们根据 CAR T 细胞治疗前的苯达莫司汀暴露情况报告了不同的结果。
该研究纳入了来自七个欧洲地点的 CAR T 细胞受者。根据单采术前行苯达莫司汀暴露情况分析安全性、疗效和 CAR T 细胞扩增动力学。对洗脱期和苯达莫司汀剂量的影响进行了额外的研究。对苯达莫司汀暴露组和苯达莫司汀未暴露组之间的所有疗效比较进行了逆概率治疗加权（IPTW）和倾向评分匹配（PSM）分析。
该研究纳入了 439 例接受 CD19 靶向商业 CAR T 细胞输注的 R/R LBCL 患者，其中 80 例在单采术前行苯达莫司汀治疗。暴露组患者在单采术时的 CD3 细胞和血小板明显更低。与苯达莫司汀未暴露组相比，这些患者的总缓解率（ORR，53%72%；<0.01）、无进展生存期（PFS，3.16.2 个月；=0.04）和总生存期（OS，10.323.5 个月；=0.01）均显著降低。在对基线变量进行调整方法后，这些差异得到缓解。在关注单采术前行苯达莫司汀洗脱的影响时，最近（<9 个月）暴露的患者（N=42）的 ORR（40%72%；<0.01）、PFS（1.36.2 个月；<0.01）和 OS（4.623.5 个月；<0.01）与苯达莫司汀未暴露患者相比显著降低。这些差异在 IPTW 和 PSM 分析后仍然显著。相反，单采术前行苯达莫司汀的累积剂量并未影响 CAR-T 疗效结果。
单采术前行苯达莫司汀暴露与 CD19 靶向 CAR T 细胞治疗后的负面治疗结果相关，因此在 CAR T 细胞候选者中应避免使用。
