DataSheet_1_Induction treatment in high-grade B-cell lymphoma with a concurrent MYC and BCL2 and/or BCL6 rearrangement: a systematic review and meta-analysis.docx

Background and aimHigh-grade B cell lymphomas with concomitant MYC and BCL2 and/or BCL6 rearrangements (HGBCL-DH/TH) have a poor prognosis when treated with the standard R-CHOP-like chemoimmunotherapy protocol. Whether this can be improved using intensified regimens is still under debate. However, due to the rarity of HGBCL-DH/TH there are no prospective, randomized controlled trials (RCT) available. Thus, with this systematic review and meta-analysis we attempted to compare survival in HGBCL-DH/TH patients receiving intensified vs. R-CHOP(-like) regimens.MethodsThe PubMed and Web of Science databases were searched for original studies reporting on first-line treatment in HGBCL-DH/TH patients from 08/2014 until 04/2022. Studies with only localized stage disease, ≤10 patients, single-arm, non-full peer-reviewed publications, and preclinical studies were excluded. The quality of literature and the risk of bias was assessed using the Methodological Index for Non-Randomized Studies (MINORS) and National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Random-effect models were used to compare R-CHOP-(like) and intensified regimens regarding 2-year overall survival (2y-OS) and 2-year progression-free survival (2y-PFS).ResultsAltogether, 11 retrospective studies, but no RCT, with 891 patients were included. Only four studies were of good quality based on aforementioned criteria. Intensified treatment could improve 2y-OS (hazard ratio [HR]=0.78 [95% confidence interval [CI] 0.63-0.96]; p=0.02) as well as 2y-PFS (HR=0.66 [95% CI 0.44-0.99]; p=0.045).ConclusionsThis meta-analysis indicates that intensified regimens could possibly improve 2y-OS and 2y-PFS in HGBCL-DH/TH patients. However, the significance of these results is mainly limited by data quality, data robustness, and its retrospective nature. There is still a need for innovative controlled clinical trials in this difficult to treat patient population.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022313234.

背景与目的：伴发MYC和BCL2以及/或BCL6重排（HGBCL-DH/TH）的高级别B细胞淋巴瘤在接受标准R-CHOP类化疗免疫治疗方案时预后较差。然而，关于是否可以通过加强治疗方案来改善预后，尚存在争议。鉴于HGBCL-DH/TH的罕见性，目前尚无前瞻性、随机对照试验（RCT）可供参考。因此，本研究通过系统综述和荟萃分析，旨在比较接受加强治疗与R-CHOP（类似）方案的HGBCL-DH/TH患者的生存情况。
方法：通过PubMed和Web of Science数据库检索了自2014年8月至2022年4月期间报道HGBCL-DH/TH患者一线治疗的原始研究。排除仅限于局部阶段疾病、患者数量≤10人、单臂研究、非全文同行评审出版物和临床前研究。使用非随机研究方法论指数（MINORS）和国家心脏、肺和血液研究所（NHLBI）观察性队列和横断面研究质量评估工具对文献质量及偏倚风险进行了评估。采用随机效应模型比较了R-CHOP（类似）方案与加强治疗方案在2年总生存期（2y-OS）和2年无进展生存期（2y-PFS）方面的差异。
结果：共纳入11项回顾性研究，但无RCT，涉及患者891例。根据上述标准，仅4项研究质量良好。加强治疗可显著提高2y-OS（风险比[HR]=0.78 [95%置信区间[CI] 0.63-0.96]; p=0.02）以及2y-PFS（HR=0.66 [95% CI 0.44-0.99]; p=0.045)。
结论：本荟萃分析表明，加强治疗方案可能有助于提高HGBCL-DH/TH患者的2年总生存期和2年无进展生存期。然而，这些结果的意义主要受限于数据质量、数据稳健性和其回顾性特征。对于这一难以治疗的病患群体，仍需开展创新的对照临床试验。
系统综述登记：https://www.crd.york.ac.uk/prospero，标识符CRD42022313234。