复发/难治性弥漫性大B细胞淋巴瘤患者接受CAR T细胞治疗后早期进展的预测因素
Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma.
作者信息
Vercellino Laetitia, Di Blasi Roberta, Kanoun Salim, Tessoulin Benoit, Rossi Cedric, D'Aveni-Piney Maud, Obéric Lucie, Bodet-Milin Caroline, Bories Pierre, Olivier Pierre, Lafon Ingrid, Berriolo-Riedinger Alina, Galli Eugenio, Bernard Sophie, Rubio Marie-Thérèse, Bossard Celine, Meignin Veronique, Merlet Pascal, Feugier Pierre, Le Gouill Steven, Ysebaert Loic, Casasnovas Olivier, Meignan Michel, Chevret Sylvie, Thieblemont Catherine
机构信息
Department of Nuclear Medicine and.
Department of Hemato-Oncology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
出版信息
Blood Adv. 2020 Nov 24;4(22):5607-5615. doi: 10.1182/bloodadvances.2020003001.
Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).
嵌合抗原受体(CAR)T细胞疗法已成为治疗失败2线治疗方案的复发/难治性侵袭性B细胞淋巴瘤的一种选择。失败通常发生在输注后早期。我们研究的目的是确定可能预测输注后第一个月内失败,特别是早期进展(EP)的因素。在决定(TD)使用商业CAR(阿基仑赛,n = 49;替雷利珠单抗,n = 67)时和治疗(TT)时分析了116例患者的特征,以及TT时的总代谢肿瘤体积(TMTV)。中位随访8.2个月,55例患者治疗失败;27例(49%)为早期进展者。估计的12个月无进展生存期(PFS)和总生存期(OS)分别为47.2%(95%置信区间[CI],38.0 - 58.6)和67.0%(95% CI,57 - 79)。PFS和OS的单因素分析确定东部肿瘤协作组体能状态(ECOG PS)≥2、III/IV期疾病、结外(EN)部位≥2、乳酸脱氢酶(LDH)升高、C反应蛋白(CRP)升高、TD和TT时的高国际预后指数,以及TT时CRP升高、肿块大、TMTV高为危险因素。PFS、EP和OS的多因素分析确定TD时LDH升高和EN部位≥2以及TT时相同的预测因素(即CRP升高、EN部位≥2和TMTV >80 mL)。总之,TD和TT时确定的早期进展危险因素是EN受累(≥2个部位)和淋巴瘤负担(LDH、TMTV)。