APHM, service de Neuro-Oncologie, Timone Hospital, CHU Timone, 264 rue saint Pierre, 13005, Marseille, France.
Aix-Marseille Université, UMR911, Marseille, France.
Ann Hematol. 2019 Apr;98(4):915-922. doi: 10.1007/s00277-018-3564-6. Epub 2018 Dec 7.
Recurrent primary central nervous system lymphomas (PCNSL) have a very poor prognosis. For young and fit patients, intensive chemotherapy followed by autologous stem cell transplantation could be proposed at relapse. In the other cases (unfit or elderly patients), therapeutic options are limited with no consensual regimen. The poly-chemotherapy by (R)-GEMOX is associated with anti-tumor activity in systemic lymphomas and a favorable toxicity profile. Our objective was to evaluate the activity and tolerance of (R)-GEMOX in PCNSL patients enrolled in the French nation-wide LOC cohort. We retrospectively analyzed all refractory or recurrent patients included in the LOC network who benefited from (R)-GEMOX (rituximab 375 mg/m, gemcitabine 1000 mg/m, and oxaliplatine 100 mg/m). Administration, tolerance, and efficacy data were analyzed. Thirteen patients, treated in five different institutions, benefited from the (R)-GEMOX regimen from February 2013 to August 2017. At the initiation of (R)-GEMOX, median age was 71.4 years old (range, 49.5-82.5) and median Karnofsky performance status (KPS) was 60 (range, 40-80). Seven patients were in second line of treatment whereas the six others were in third line or over. All patients had received methotrexate-based polychemotherapy as first-line treatment except one. Overall response rate was 38% with two complete responses and three partial responses. Median progression-free survival was 3.2 months (95%CI: 0.2-6.2), and median overall survival was 8.2 months (95%CI: 0.6-15.8). Toxicity was mainly hematological including grade ¾ neutropenia (38%), lymphopenia (23%), and thrombopenia (23%). Older age (p = 0.046) and low KPS (p = 0.054) tended to be associated with a worse prognosis. (R)-GEMOX is associated with substantial response rate and favorable toxicity profile in unfit patients with recurrent PCNSL. (R)-GEMOX could be considered to be an additional option in patients with recurrent/refractory PCNSL.
复发性原发性中枢神经系统淋巴瘤(PCNSL)的预后非常差。对于年轻且身体状况良好的患者,在复发时可以采用强化化疗联合自体干细胞移植。在其他情况下(身体状况不佳或老年患者),治疗方案有限,没有共识方案。(R)-GEMOX 联合化疗方案在全身淋巴瘤中具有抗肿瘤活性,且毒性谱良好。我们的目的是评估(R)-GEMOX 在法国全国 LOC 队列中纳入的 PCNSL 患者中的活性和耐受性。我们回顾性分析了在 LOC 网络中接受(R)-GEMOX(利妥昔单抗 375mg/m2、吉西他滨 1000mg/m2 和奥沙利铂 100mg/m2)治疗的所有难治性或复发性患者。分析了给药、耐受性和疗效数据。13 名患者在五家不同的机构接受了治疗,自 2013 年 2 月至 2017 年 8 月,接受了(R)-GEMOX 治疗。开始(R)-GEMOX 治疗时,中位年龄为 71.4 岁(范围,49.5-82.5),卡氏功能状态评分(KPS)为 60(范围,40-80)。7 例患者处于二线治疗,其余 6 例患者处于三线或以上治疗。所有患者均接受过以甲氨蝶呤为基础的联合化疗作为一线治疗,除 1 例外。总体缓解率为 38%,完全缓解 2 例,部分缓解 3 例。中位无进展生存期为 3.2 个月(95%CI:0.2-6.2),中位总生存期为 8.2 个月(95%CI:0.6-15.8)。毒性主要为血液学毒性,包括 3/4 级中性粒细胞减少症(38%)、淋巴细胞减少症(23%)和血小板减少症(23%)。年龄较大(p=0.046)和较低的 KPS(p=0.054)与预后较差相关。(R)-GEMOX 在复发性 PCNSL 患者中具有较高的反应率和良好的毒性谱,在身体状况不佳的患者中是一种有效的治疗选择。(R)-GEMOX 可以作为复发性/难治性 PCNSL 患者的附加选择。