Baird John H, Epstein David J, Tamaresis John S, Ehlinger Zachary, Spiegel Jay Y, Craig Juliana, Claire Gursharan K, Frank Matthew J, Muffly Lori, Shiraz Parveen, Meyer Everett, Arai Sally, Brown Janice Wes, Johnston Laura, Lowsky Robert, Negrin Robert S, Rezvani Andrew R, Weng Wen-Kai, Latchford Theresa, Sahaf Bita, Mackall Crystal L, Miklos David B, Sidana Surbhi
Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA; and.
Blood Adv. 2021 Jan 12;5(1):143-155. doi: 10.1182/bloodadvances.2020002732.
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count <200 cells per μL by 18 months postinfusion. Patients with durable responses to axi-cel had significantly longer durations of B-cell aplasia, and this duration correlated strongly with the recovery of CD4+ T-cell counts. There were significantly more infections within the first 28 days compared with any other period of follow-up, with the majority being mild-moderate in severity. Receipt of corticosteroids was the only factor that predicted risk of infection in a multivariate analysis (hazard ratio, 3.69; 95% confidence interval, 1.18-16.5). Opportunistic infections due to Pneumocystis jirovecii and varicella-zoster virus occurred up to 18 months postinfusion in patients who prematurely discontinued prophylaxis. These results support the use of comprehensive supportive care, including long-term monitoring and antimicrobial prophylaxis, beyond 12 months after axi-cel treatment.
靶向CD19的嵌合抗原受体（CAR）T细胞疗法显著改善了难治性或复发性大B细胞淋巴瘤（LBCL）的治疗效果。我们评估了在单一中心接受阿基仑赛注射液（axi-cel）治疗的41例LBCL患者的血液学恢复、免疫重建和感染并发症的长期病程。97.6%的患者在输注后第1个28天内出现3级及以上血细胞减少，多数在6个月时缓解。总体而言，63.4%的患者接受了红细胞输注，34.1%的患者接受了血小板输注，36.6%的患者接受了静脉注射免疫球蛋白，51.2%的患者在输注后第1个28天后接受了生长因子（粒细胞集落刺激因子）注射。仅40%的患者在1年时恢复了可检测到的CD19+B细胞，50%的患者在输注后18个月时CD4+T细胞计数<200个/μL。对axi-cel有持久反应的患者B细胞发育不全的持续时间显著更长，且这一持续时间与CD4+T细胞计数的恢复密切相关。与其他任何随访期相比，输注后第1个28天内的感染明显更多，多数感染的严重程度为轻至中度。在多变量分析中，接受皮质类固醇治疗是唯一预测感染风险的因素（风险比，3.69；95%置信区间，1.18-16.5）。在过早停止预防的患者中，输注后长达18个月发生了由耶氏肺孢子菌和水痘-带状疱疹病毒引起的机会性感染。这些结果支持在axi-cel治疗后12个月以上使用全面的支持性护理，包括长期监测和抗菌预防。
