Linear Clinical Research, Nedlands, WA, Australia.
Division of Haematology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
J Clin Oncol. 2023 Dec 10;41(35):5376-5387. doi: 10.1200/JCO.23.00365. Epub 2023 Oct 5.
CNS progression or relapse is an uncommon but devastating complication of aggressive B-cell lymphoma. There is no consensus regarding the optimal approach to CNS prophylaxis. This study was designed to determine whether high-dose methotrexate (HD-MTX) is effective at preventing CNS progression in patients at high risk of this complication.
Patients age 18-80 years with aggressive B-cell lymphoma and high risk of CNS progression, treated with curative-intent anti-CD20-based chemoimmunotherapy, were included in this international, retrospective, observational study. Cause-specific hazard ratios (HRs) and cumulative risks of CNS progression were calculated according to use of HD-MTX, with time to CNS progression calculated from diagnosis for all patients (all-pts) and from completion of frontline systemic lymphoma induction therapy, for patients in complete response at completion of chemoimmunotherapy (CR-pts).
Two thousand four hundred eighteen all-pts (HD-MTX; n = 425) and 1,616 CR-pts (HD-MTX; n = 356) were included. CNS International Prognostic Index was 4-6 in 83.4% all-pts. Patients treated with HD-MTX had a lower risk of CNS progression (adjusted HR, 0.59 [95% CI, 0.38 to 0.90]; = .014), but significance was not retained when confined to CR-pts (adjusted HR, 0.74 [95% CI, 0.42 to 1.30]; = .29), with 5-year adjusted risk difference of 1.6% (95% CI, -1.5 to 4.4; all-pts) and 1.4% (95% CI, -1.5 to 4.1; CR-pts). Subgroups were underpowered to draw definitive conclusions regarding the efficacy of HD-MTX in individual high-risk clinical scenarios; however, there was no clear reduction in CNS progression risk with HD-MTX in any high-risk subgroup.
In this large study, high-risk patients receiving HD-MTX had a 7.2% 2-year risk of CNS progression, consistent with the progression risk in previously reported high-risk cohorts. Use of HD-MTX was not associated with a clinically meaningful reduction in risk of CNS progression.
中枢神经系统（CNS）进展或复发是侵袭性 B 细胞淋巴瘤的一种罕见但破坏性的并发症。对于中枢神经系统预防，目前尚无共识。本研究旨在确定大剂量甲氨蝶呤（HD-MTX）是否可有效预防高危 CNS 进展的患者发生 CNS 进展。
纳入年龄在 18-80 岁之间、患有侵袭性 B 细胞淋巴瘤且具有高危 CNS 进展风险、接受以 CD20 为基础的治愈性化疗免疫治疗的患者，这些患者来自国际、回顾性、观察性研究。根据 HD-MTX 的使用情况，计算 CNS 进展的特定原因风险比（HR）和累积风险，所有患者（所有患者）从诊断开始计算 CNS 进展时间，完全缓解完成化疗免疫治疗的患者（CR-pts）从完成一线全身淋巴瘤诱导治疗开始计算。
共纳入 2418 例所有患者（HD-MTX；n = 425）和 1616 例 CR-pts（HD-MTX；n = 356）。83.4%的所有患者的中枢神经系统国际预后指数为 4-6。接受 HD-MTX 治疗的患者发生 CNS 进展的风险较低（校正 HR，0.59[95%CI，0.38 至 0.90]；P =.014），但仅限于 CR-pts 时，其无统计学意义（校正 HR，0.74[95%CI，0.42 至 1.30]；P =.29），5 年校正风险差异为 1.6%（95%CI，-1.5 至 4.4；所有患者）和 1.4%（95%CI，-1.5 至 4.1；CR-pts）。亚组分析的效能不足以得出关于 HD-MTX 在个别高危临床情况下疗效的明确结论；然而，在任何高危亚组中，HD-MTX 均不能明显降低 CNS 进展风险。
在这项大型研究中，接受 HD-MTX 治疗的高危患者的 2 年 CNS 进展风险为 7.2%，与之前报告的高危队列的进展风险一致。使用 HD-MTX 并未降低 CNS 进展的风险。
