Hermine Olivier, Jiang Linmiao, Walewski Jan, Bosly André, Thieblemont Catherine, Szymczyk Michal, Pott Christiane, Salles Gilles, Feugier Pierre, Hübel Kai, Haioun Corinne, Casasnovas René Olivier, Schmidt Christian, Bouabdallah Kamal, Ribrag Vincent, Kanz Lothar, Dürig Jan, Metzner Bernd, Sibon David, Cheminant Morgane, Burroni Barbara, Klapper Wolfram, Hiddemann Wolfgang, Unterhalt Michael, Hoster Eva, Dreyling Martin
Department Hematology, Hôpital Necker, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France.
INSERM U1163 and CNRS 8254, Imagine Institute, Université Sorbonne Paris Cité, Paris, France.
J Clin Oncol. 2023 Jan 20;41(3):479-484. doi: 10.1200/JCO.22.01780. Epub 2022 Dec 5.
JCO In 2004, the European Mantle Cell Lymphoma (MCL) Network initiated the randomized open-label, phase III MCL Younger trial for first-line treatment of patients with advanced-stage MCL, age < 66 years, comparing an alternating rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone/rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-CHOP/R-DHAP) induction followed by high-dose cytarabine-containing myeloablative radiochemotherapy conditioning and autologous peripheral blood stem-cell transplantation (R-DHAP arm) to R-CHOP with standard myeloablative radiochemotherapy and autologous stem-cell transplantation (R-CHOP arm). After a median follow-up of 10.6 years, the time to treatment failure was still significantly improved in the R-DHAP versus R-CHOP arms (medians 8.4 3.9 years, 5-/10-year rates 64%/46% 41%/25%, = .038, hazard ratio, 0.59). Median overall survival (OS) was not reached in the R-DHAP arm versus 11.3 years in R-CHOP arm (5-/10-year rates, 76%/60% 69%/55%, = .12). The unadjusted OS hazard ratios (0.80 [95% CI, 0.61 to 1.06], = .12) reached significance when adjusted for Mantle Cell Lymphoma International Prognostic Index (MIPI) and MIPI + Ki-67 (MIPI-c) (0.74; 95% CI, 0.56 to 0.98; = .038 and .60; 95% CI, 0.41 to 0.87; = .0066). The incidence of secondary hematologic malignancies tended to be higher in the R-DHAP arm (4.5% 1.4% at 10 years). With mature long-term data, we confirm the previously observed substantially prolonged time to treatment failure and, for the first time to our knowledge, show an improvement of OS. Some patients with MCL may be cured.
2004年，欧洲套细胞淋巴瘤（MCL）网络启动了一项随机开放标签的III期MCL Younger试验，用于一线治疗年龄<66岁的晚期MCL患者，比较交替使用利妥昔单抗加环磷酰胺、阿霉素、长春新碱和泼尼松/利妥昔单抗加地塞米松、大剂量阿糖胞苷和顺铂（R-CHOP/R-DHAP）诱导，随后进行含大剂量阿糖胞苷的清髓性放化疗预处理和自体外周血干细胞移植（R-DHAP组）与采用标准清髓性放化疗和自体干细胞移植的R-CHOP（R-CHOP组）。中位随访10.6年后，R-DHAP组与R-CHOP组相比，治疗失败时间仍有显著改善（中位值8.4对3.9年，5年/10年发生率64%/46%对41%/25%，P = 0.038，风险比，0.59）。R-DHAP组未达到中位总生存期（OS），而R-CHOP组为11.3年（5年/10年发生率，76%/60%对69%/55%，P = 0.12）。当根据套细胞淋巴瘤国际预后指数（MIPI）和MIPI + Ki-67（MIPI-c）进行调整时，未调整的OS风险比（0.80 [95% CI，0.61至1.06]，P = 0.12）达到显著水平（0.74；95% CI, 0.56至0.98；P = 0.038和0.60；95% CI，0.41至0.87；P = 0.0066）。R-DHAP组继发性血液系统恶性肿瘤的发生率在10年时趋于更高（4.5%对1.4%）。有了成熟的长期数据，我们证实了之前观察到的治疗失败时间大幅延长，并且据我们所知首次显示出OS的改善。一些MCL患者可能被治愈。
