Epperla Narendranath, Reljic Tea, Chowdhury Sayan Mullick, Ferreri Andrés J M, Kumar Ambuj, Hamadani Mehdi
Division of Hematology, Department of Medicine, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio, USA.
Department of Internal Medicine, Research Methodology and Biostatistics Core, Office of Research, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
Hematol Oncol. 2023 Feb;41(1):88-96. doi: 10.1002/hon.3083. Epub 2022 Oct 6.
The management of newly diagnosed primary central nervous system lymphoma (PCNSL) includes administration of high-dose methotrexate based regimens followed by consolidation therapy to minimize the risk of relapse. However, the best consolidation strategy (autologous hematopoietic cell transplant [auto-HCT] vs. whole-brain radiotherapy [WBRT]) is controversial. Hence, we performed a systematic review and meta-analysis of all randomized controlled trials that compared auto-HCT versus WBRT consolidation for patients with PCNSL after first-line treatment.The primary outcome was overall survival (OS), while the secondary outcomes included progression-free survival (PFS), response rates (overall response rate [ORR] and complete remission [CR]), relapse rate, treatment-related mortality (TRM), and neuropsychological adverse events. We performed a pooled analysis of the single-arm studies that incorporated auto-HCT or WBRT consolidation and evaluated neurocognitive outcomes. Only two studies met the inclusion criteria (n = 240). There was no significant difference in OS (HR = 1.50; 95% CI = 0.95-2.36), PFS (HR = 0.99; 95% CI = 0.44-2.22), ORR (RR = 1.48; 95% CI = 0.90-2.44), CR rate (RR = 1.21; 95% CI = 0.90-1.63), relapse rate (RR = 0.46; 95% CI = 0.05-4.28), and TRM (RR = 5.67; 95% CI = 1.01-31.91). The neuropsychological tests to assess neurocognitive domains were different and inconsistently reported in the two studies and therefore we were unable to perform a meta-analysis but provide a descriptive assessment. Both the studies showed a significant decline in the attention/executive function (based on the trail making test A and trail making test B) in those receiving WBRT compared to auto-HCT. We found 9 single-arm phase II studies that reported data on outcomes associated with either auto-HCT (5 studies) or WBRT (4 studies) consolidation. Of these, two studies (n = 43) reported data on neurocognitive decline following auto-HCT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 6% (95% CI, 0%-17%) for those receiving auto-HCT and there was no heterogeneity between studies (I = 0%). Three studies (n = 122) reported data on neurocognitive decline following WBRT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 43% (95% CI, 11%-78%) for those receiving WBRT and there was high heterogeneity between studies (I = 94%). There was significant heterogeneity between subgroups (p = 0.035). The outcomes were not significantly different in patients with PCNSL receiving auto-HCT or WBRT consolidation therapies, however, there is a higher degree of neurocognitive decline associated with WBRT compared to auto-HCT consolidation. The decision to choose a consolidation strategy needs to be individualized based on age, frailty, and co-morbidities.
新诊断的原发性中枢神经系统淋巴瘤（PCNSL）的管理包括给予基于大剂量甲氨蝶呤的方案，随后进行巩固治疗以尽量降低复发风险。然而，最佳的巩固策略（自体造血细胞移植[auto-HCT]与全脑放疗[WBRT]）存在争议。因此，我们对所有比较一线治疗后PCNSL患者auto-HCT与WBRT巩固治疗的随机对照试验进行了系统评价和荟萃分析。主要结局是总生存期（OS），次要结局包括无进展生存期（PFS）、缓解率（总缓解率[ORR]和完全缓解[CR]）、复发率、治疗相关死亡率（TRM）以及神经心理不良事件。我们对纳入了auto-HCT或WBRT巩固治疗的单臂研究进行了汇总分析，并评估了神经认知结局。仅有两项研究符合纳入标准（n = 240）。在OS（HR = 1.50；95%CI = 0.95 - 2.36）、PFS（HR = 0.99；95%CI = 0.44 - 2.22）、ORR（RR = 1.48；95%CI = 0.90 - 2.44）、CR率（RR = 1.
