Houillier Caroline, Ghesquières Hervé, Chabrot Cécile, Soussain Carole, Ahle Guido, Choquet Sylvain, Nicolas-Virelizier Emmanuelle, Bay Jacques-Olivier, Vargaftig Jacques, Gaultier Claude, Touitou Valérie, Martin-Duverneuil Nadine, Cassoux Nathalie, Le Garff-Tavernier Magali, Costopoulos Myrto, Faurie Pierre, Hoang-Xuan Khê
Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, APHP, Sorbonne Universités UPMC Universités Paris VI, IHU, ICM, 47-83 boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
Service d'hématologie, Centre Léon Bérard, 28 rue Laennec, 69008, Lyon, France.
J Neurooncol. 2017 Jun;133(2):315-320. doi: 10.1007/s11060-017-2435-7. Epub 2017 Apr 21.
Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3.5 g/m D1, D15), procarbazine, vincristine, followed by three 28-day cycles of cytarabine consolidation (3 g/m D1-2). Addition of rituximab (375 mg/m D1) was optional. The results were compared with the historical MPV-A regimen. Ninety patients received the (R)-MPV-AAA regimen with (n = 39) or without (n = 51) rituximab. Median age was 68 and median KPS 60. 55% of patients achieved a complete response, 8% a partial response and 37% progressed. The median PFS was 10 months, the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of grade III-IV neutropenia and thrombopenia. The response rate was higher in patients receiving rituximab (77 vs. 53%; p = 0.03), whereas no difference was observed in terms of PFS or OS. When comparing the results to the historical MPV-A, there was no difference in terms of response rate, PFS or OS, but a higher rate of hematotoxicity. This study suggests that extending cytarabine consolidation after methotrexate-based chemotherapy does not improve the MPV-A efficacy but increases toxicity in the elderly. The addition of rituximab may improve the response rate, but its impact on final outcome remains unclear.
原发性中枢神经系统淋巴瘤(PCNSL)对基于大剂量甲氨蝶呤的化疗敏感。然而,老年患者的缓解持续时间短且预后较差。鉴于放疗和强化化疗会使老年人面临严重毒性,需要评估替代巩固治疗方法。在这项多中心研究中,我们回顾性分析了年龄>60岁、接受(R)-MPV-AAA方案治疗的新诊断PCNSL连续患者。该方案包括三个28天周期的甲氨蝶呤(3.5 g/m² D1、D15)、丙卡巴肼、长春新碱,随后是三个28天周期的阿糖胞苷巩固治疗(3 g/m² D1-2)。可选择添加利妥昔单抗(375 mg/m² D1)。将结果与历史MPV-A方案进行比较。90例患者接受了(R)-MPV-AAA方案,其中39例使用利妥昔单抗,51例未使用。中位年龄为68岁,中位KPS为60。55%的患者达到完全缓解,8%部分缓解,37%进展。中位无进展生存期为10个月,中位总生存期为28.1个月。毒性主要为血液学毒性,III-IV级中性粒细胞减少和血小板减少分别为54%和51%。接受利妥昔单抗的患者缓解率更高(77%对53%;p = 0.03),而在无进展生存期或总生存期方面未观察到差异。与历史MPV-A方案比较,缓解率、无进展生存期或总生存期无差异,但血液毒性发生率更高。这项研究表明,在基于甲氨蝶呤的化疗后延长阿糖胞苷巩固治疗并不能提高MPV-A方案的疗效,但会增加老年患者的毒性。添加利妥昔单抗可能会提高缓解率,但其对最终结局的影响仍不清楚。