de Boer Janneke W., Keijzer Kylie, van Dorp Suzanne, Mutsaers Pim G.N.J., Niezink Anne G.H., van Doesum Jaap A., Serroukh Yasmina I.M., Muntendam Louise W., Pulles Astrid E., Kret Esther J., Sijs-Szabo Aniko, Oomen Jesse, Demandt Astrid M.P., Stevens Wendy B.C., Kuipers Maria T., Pennings Elise R.A., Spanjaart Anne M., Kersten Marie José, Jak Margot, van Dijk Lisanne V., van der Poel Marjolein W.M., Vermaat Joost S.P., van Meerten Tom
University Medical Center Groningen, Groningen, Netherlands.
University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Blood Adv. 2025 Jul 16. doi: 10.1182/bloodadvances.2025016689.
Early identification of patients at risk for immune effector cell-associated hematotoxicity (ICAHT) is essential to minimize non-relapse mortality. The CAR-HEMATOTOX (HT) score is an implemented risk-stratification tool for ICAHT, infections and survival in relapsed/refractory large B-cell lymphoma (R/R LBCL) patients receiving CAR T-cell therapy (CART). Although validated in its defining study, the HT score was developed in a small cohort, necessitating independent external validation. This study externally validates the HT score in a real-world population-based cohort of adults with R/R LBCL receiving CART. The HT score, based on absolute neutrophil count, hemoglobin, platelets, C-reactive protein, and ferritin, was calculated before lymphodepleting chemotherapy. Of 245 consecutive patients, 171 (70%) had a HT score ≥2 (HThigh). The initial endpoint, clinically significant neutropenia (ANC < 500/µL for ≥14 days), occurred in 21% of patients. The binary HT score was associated with clinically significant neutropenia (OR 2.94 [95%CI 1.27-6.80]; P = 0.012) with a good predictive performance (AUC = 0.73). Similar results were achieved for early and late ICAHT ≥ grade 3 (OR 2.92, [95% CI 1.19 - 7.14]; P = 0.019; OR 2.42 [95% CI 1.31 - 4.47]; P = 0.005). A trend towards an association with severe infections was observed (OR 2.02 [95%CI 0.91-4.48], P = 0.085). HThigh patients had a lower progression-free and overall survival (HRs 1.84 [95%CI 1.15-2.93]; P = 0.011, and 2.83 [95%CI 1.64-4.87]; P < 0.001, respectively). The HT score identified CART-treated R/R LBCL patients at risk for clinically significant neutropenia, poor survival outcomes, and potentially severe infections.
早期识别有免疫效应细胞相关血液毒性（ICAHT）风险的患者对于将非复发死亡率降至最低至关重要。CAR-HEMATOTOX（HT）评分是一种已实施的风险分层工具，用于接受CAR T细胞疗法（CART）的复发/难治性大B细胞淋巴瘤（R/R LBCL）患者的ICAHT、感染和生存情况评估。尽管在其定义性研究中得到了验证，但HT评分是在一个小队列中开发的，因此需要独立的外部验证。本研究在一个基于真实世界人群的接受CART治疗的R/R LBCL成年队列中对HT评分进行了外部验证。HT评分基于绝对中性粒细胞计数、血红蛋白、血小板、C反应蛋白和铁蛋白，在淋巴细胞清除化疗前进行计算。在245例连续患者中，171例（70%）的HT评分≥2（HT高）。初始终点，即临床上显著的中性粒细胞减少（中性粒细胞绝对值<500/µL持续≥14天），发生在21%的患者中。二元HT评分与临床上显著的中性粒细胞减少相关（比值比2.94[95%置信区间1.27 - 6.80]；P = 0.012），预测性能良好（曲线下面积 = 0.73）。对于早期和晚期ICAHT≥3级，也得到了类似结果（比值比2.92，[95%置信区间1.19 - 7.14]；P = 0.019；比值比2.42[95%置信区间1.31 - 4.47]；P = 0.005）。观察到与严重感染存在关联趋势（比值比2.02[95%置信区间0.91 - 4.48]，P = 0.085）。HT高的患者无进展生存期和总生存期较低（风险比分别为1.84[95%置信区间1.15 - 2.93]；P = 0.011，以及2.83[95%置信区间1.64 - 4.87]；P < 0.001）。HT评分识别出接受CART治疗的R/R LBCL患者有临床上显著中性粒细胞减少、生存结果差和潜在严重感染的风险。
