RainCity Analytics, Vancouver, BC, Canada.
Gilead Sciences Canada, Inc., Mississauga, Canada.
BMC Cancer. 2023 Jan 23;23(1):74. doi: 10.1186/s12885-023-10546-6.
Patients with follicular lymphoma (FL) can have high response rates to early lines of treatment. However, among FL patients relapsed/refractory (r/r) after ≥2 prior lines of therapy (LOT), remission tends to be shorter and there is limited treatment guidance. This study sought to evaluate the clinical outcomes for r/r FL after ≥2 prior LOT identified through systematic literature review.
Eligible studies included comparative or non-comparative interventional or observational studies of systemic therapies among adults with FL r/r after ≥2 prior LOT published prior to 31st May 2021. Prior LOT must have included an anti-CD20 monoclonal antibody and an alkylating agent, in combination or separately. Overall response rate (ORR) and complete response (CR) were estimated using inverse-variance weighting with Freeman-Tukey double-arcsine transformations. Kaplan-Meier (KM) curves for progression-free survival (PFS) and overall survival (OS) estimated by reconstructing digitized curves using the Guyot algorithm, and survival analyses were conducted, stratified by ≥2 prior LOT and ≥ 3 prior LOT groups (as defined in the source material). Restricting the analyses to the observational cohorts was investigated as a sensitivity analysis.
The analysis-set included 20 studies published between 2014 and 2021. Studies were primarily US and/or European based, with the few exceptions using treatments approved in US/Europe. The estimated ORR was 58.47% (95% confidence interval [CI]: 51.13-65.62) and proportion of patients with CR was 19.63% (95% CI: 15.02-24.68). The median OS among those ≥2 prior LOT was 56.57 months (95% CI: 47.8-68.78) and median PFS was 9.78 months (95% CI: 9.01-10.63). The 24-month OS decreased from 66.50% in the ≥2 prior LOT group to 59.51% in the ≥3 prior LOT group, with a similar trend in PFS at 24-month (28.42% vs 24.13%).
This study found that few r/r FL patients with ≥2 prior LOT achieve CR, and despite some benefit, approximately 1/3 of treated patients die within 24 months. The shorter median PFS with increasing prior LOT suggest treatment durability is suboptimal in later LOT. These findings indicate that patients are underserved by treatments currently available in the US and Europe.
滤泡性淋巴瘤 (FL) 患者在早期治疗线中可获得较高的缓解率。然而，在≥2 线治疗后复发/难治 (r/r) 的 FL 患者中，缓解时间往往较短，治疗指导有限。本研究通过系统文献回顾，评估了≥2 线治疗后 r/r FL 的临床结局。
合格的研究包括在≥2 线治疗后 r/r FL 成人中进行的系统治疗的比较或非比较干预或观察性研究，这些研究在 2021 年 5 月 31 日之前发表。既往 LOT 必须包括抗 CD20 单克隆抗体和烷化剂，联合或单独使用。使用逆方差加权法和 Freeman-Tukey 双弧形变换估计总缓解率 (ORR) 和完全缓解率 (CR)。使用 Guyot 算法重建数字化曲线估计无进展生存期 (PFS) 和总生存期 (OS) 的 Kaplan-Meier (KM) 曲线，并进行生存分析，按≥2 线和≥3 线 LOT 组分层（如原始资料中定义）。还对将分析限于观察队列进行了敏感性分析。
分析集包括 2014 年至 2021 年发表的 20 项研究。这些研究主要是在美国和/或欧洲进行的，只有少数例外情况是使用在美国/欧洲批准的治疗方法。估计的 ORR 为 58.47%（95%置信区间 [CI]：51.13-65.62），CR 患者比例为 19.63%（95% CI：15.02-24.68）。≥2 线 LOT 的中位 OS 为 56.57 个月（95% CI：47.8-68.78），中位 PFS 为 9.78 个月（95% CI：9.01-10.63）。≥2 线 LOT 组的 24 个月 OS 从 66.50%下降至≥3 线 LOT 组的 59.51%，24 个月时 PFS 也呈类似趋势（28.42%比 24.13%）。
本研究发现，≥2 线治疗后 r/r FL 患者中很少有患者达到 CR，尽管有一定疗效，但大约 1/3 的治疗患者在 24 个月内死亡。随着既往 LOT 的增加，中位 PFS 缩短，提示后续 LOT 的治疗持久性欠佳。这些发现表明，美国和欧洲目前可用的治疗方法未能满足患者的需求。
