Department of Hematology, UMR CNRS 5535, University Hospital, Montpellier, France.
Department of Hematology, University Hospital, Lyon, France.
J Clin Oncol. 2023 Jul 1;41(19):3523-3533. doi: 10.1200/JCO.22.02327. Epub 2023 Apr 18.
Rituximab improves progression-free survival (PFS) and time to next treatment (TTNT) when compared with the watch and wait strategy for patients with low-tumor burden follicular lymphoma (FL). Prolonged rituximab maintenance did not prolong TTNT, whereas it raises concerns about resources use and patient adhesion. Our aim was then to investigate the use of short rituximab maintenance using the subcutaneous (SC) route in patients with low-tumor burden FL.
Patients with histologically confirmed CD20 low-tumor burden FL were randomly assigned to receive either rituximab, 375 mg/m once daily on D1, D8, D15, and D22, intravenous route (IV, control arm), or rituximab, 375 mg/m, on day 1 (D1), IV followed by rituximab 1,400 mg total dose, SC once daily on D8, D15, and D22, with maintenance at months 3 (M3), M5, M7, and M9 (experimental arm). The primary end point was PFS. Secondary end points included safety, overall response rates, TTNT, and overall survival (OS).
Two hundred two patients with low-tumor burden FL were randomly assigned to the experimental (n = 100) or control arm (n = 102). The primary end point was met: the 4-year PFS was 58.1% (95% CI, 47.5 to 67.4) and 41.2% (95% CI, 30.6 to 51.6) in experimental and control arms, respectively (hazard ratio, 0.585 [0.393 to 0.871]; = .0076). Complete response (CR) rates were 59.0% (95% CI, 48.7 to 68.7) in the experimental arm and 36.3% (95% CI, 27.0 to 46.4) in the control arm ( = .001). TTNT and OS were not significantly different. CR was associated with longer PFS and TTNT. High rituximab exposure during the first three months was independently associated with higher CR, PFS, and TTNT.
SC rituximab improves PFS for patients with low-tumor burden FL when used in induction followed by short maintenance. High rituximab exposure during the first 3 months after treatment initiation is, however, the only parameter influencing patient outcomes.
与观察等待策略相比，利妥昔单抗可改善低肿瘤负担滤泡性淋巴瘤（FL）患者的无进展生存期（PFS）和下一次治疗时间（TTNT）。延长利妥昔单抗维持治疗并未延长 TTNT，但这引起了人们对资源利用和患者依从性的关注。因此，我们的目的是研究低肿瘤负担 FL 患者使用皮下（SC）途径的短利妥昔单抗维持治疗。
经组织学证实的 CD20 低肿瘤负担 FL 患者被随机分配接受利妥昔单抗 375mg/m 静脉注射（IV，对照组），每日一次，于第 1、8、15 和 22 天（D1、D8、D15 和 D22），或利妥昔单抗 375mg/m，于第 1 天（D1），IV 后给予利妥昔单抗 1400mg 总剂量，每日一次，于第 8、15 和 22 天 SC，维持治疗在第 3（M3）、5（M5）、7（M7）和 9（M9）个月（实验组）。主要终点为 PFS。次要终点包括安全性、总缓解率、TTNT 和总生存期（OS）。
202 例低肿瘤负担 FL 患者被随机分配至实验组（n=100）或对照组（n=102）。主要终点达到：实验组 4 年 PFS 为 58.1%（95%CI，47.5 至 67.4），对照组为 41.2%（95%CI，30.6 至 51.6）（风险比，0.585[0.393 至 0.871]；=0.0076）。实验组完全缓解（CR）率为 59.0%（95%CI，48.7 至 68.7），对照组为 36.3%（95%CI，27.0 至 46.4）（=0.001）。TTNT 和 OS 无显著差异。CR 与更长的 PFS 和 TTNT 相关。治疗开始后前 3 个月高的利妥昔单抗暴露与更高的 CR、PFS 和 TTNT 相关。
低肿瘤负担 FL 患者诱导后使用 SC 利妥昔单抗进行短期维持治疗可改善 PFS。然而，治疗开始后前 3 个月高的利妥昔单抗暴露是影响患者结局的唯一参数。
