Université de Paris, Assistance Publique-Hôpitaux de Paris (APHP), Hemato-oncologie, Saint-Louis Hôpital, Paris, France.
Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany.
Blood Adv. 2023 Aug 8;7(15):3968-3977. doi: 10.1182/bloodadvances.2022008888.
Most patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Patients with progression or relapse in the central nervous system (CNS) face dismal outcomes. The impact of more aggressive regimens used in frontline therapy has not been systematically investigated in this context. To this end, we analyzed a large cohort of 2203 younger patients with DLBCL treated on 10 German (German Lymphoma Alliance [GLA]/The German High Grade Non-Hodgkin's Lymphoma Study Group [DSHNHL]) and French (The Lymphoma Study Association [LYSA]) prospective phase 2 and 3 trials after first-line therapy with R-CHOP, R-CHOEP (R-CHOP + etoposide), dose-escalated R-CHOEP followed by repetitive stem cell transplantation (R-MegaCHOEP), or R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycine, and prednisone) followed by consolidation including multiple drugs crossing the blood-brain barrier (BBB). Patients with DLBCL with an age-adjusted International Prognostic Index (aaIPI) of 0 to 1 showed very low cumulative incidence rates of CNS relapse regardless of first-line therapy and CNS prophylaxis (3-year cumulative incidences 0%-1%). Younger high-risk patients with aaIPI of 2 to 3 had 3-year cumulative incidence rates of 1.6% and 4% after R-ACVBP plus consolidation or R-(Mega)CHO(E)P, respectively (hazard ratio 2.4; 95% confidence interval: 0.8-7.4; P = .118). Thus, for younger high-risk patients, frontline regimens incorporating agents crossing the BBB may reduce often fatal CNS relapse.
大多数弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者可以通过免疫化疗（如 R-CHOP [利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松]）治愈。中枢神经系统 (CNS) 进展或复发的患者预后较差。在这种情况下，尚未系统研究一线治疗中使用更具侵袭性方案的影响。为此，我们分析了 2203 名年轻 DLBCL 患者的大型队列，这些患者在德国（德国淋巴瘤联盟 [GLA]/德国高级非霍奇金淋巴瘤研究组 [DSHNHL]）和法国（淋巴瘤研究协会 [LYSA]）的 10 项前瞻性 2 期和 3 期试验中接受了一线 R-CHOP、R-CHOEP（R-CHOP+依托泊苷）、剂量递增的 R-CHOEP 序贯重复干细胞移植（R-MegaCHOEP）、或 R-ACVBP（利妥昔单抗、多柔比星、环磷酰胺、长春新碱、博来霉素和泼尼松）治疗，随后进行巩固治疗，包括多种穿透血脑屏障（BBB）的药物。年龄调整国际预后指数（aaIPI）为 0 至 1 的 DLBCL 患者，无论一线治疗和中枢神经系统预防如何，中枢神经系统复发的累积发生率都非常低（3 年累积发生率为 0%-1%）。aaIPI 为 2 至 3 的年轻高危患者，在接受 R-ACVBP 联合巩固治疗或 R-(Mega)CHO(E)P 治疗后，3 年累积发生率分别为 1.6%和 4%（风险比 2.4；95%置信区间：0.8-7.4；P=.118）。因此，对于年轻的高危患者，包含穿透 BBB 药物的一线方案可能会降低中枢神经系统复发这一致命并发症的发生率。
