Sorigue Marc, Mercadal Santiago, Alonso Sara, Fernández-Álvarez Ruben, García Olga, Moreno Miriam, Pomares Helena, Alcoceba Miguel, González-García Esther, Motlló Cristina, González-Barca Eva, Martin Alejandro, Sureda Anna, Caballero Dolores, Ribera Josep-María, Sancho Juan-Manuel
Department of Hematology. ICO-Badalona, Hospital Germans Trias i Pujol, Institut de Recerce Josep Carreras, Universitat Autònoma de Barcelona, Badalona, Spain.
Department of Hematology. ICO-Duran y Reynals, Hospitalet de Llobregat, Bacelona, Spain.
Hematol Oncol. 2017 Dec;35(4):520-527. doi: 10.1002/hon.2378. Epub 2017 Feb 3.
Follicular lymphoma is characterized by a good response to immunochemotherapy (ICT). However, a small percentage of patients responds poorly to treatment and seems to have a worse outcome. This study attempted to identify the predictive factors and outcome of refractoriness to first-line ICT. All patients diagnosed with stage II to IV follicular lymphoma between 2002 and 2014 and treated with first-line ICT in 4 Spanish institutions were analyzed. Those with no response or progression or relapse within 6 months of first-line response assessment were considered ICT refractory. Three hundred forty-three patients were included (median age 58 years, 48% male), of whom 53 (15%) were ICT refractory. On multivariate analysis, high-risk follicular lymphoma international prognostic index (FLIPI) score, B symptoms, and elevated β2-microglobulin were correlated with refractoriness, and refractoriness, high-risk FLIPI score, and β2-microglobulin were correlated with overall survival (OS). Compared with ICT-sensitive, ICT-refractory patients had a higher incidence of histological transformation (5-year cumulative incidence 25% [14%-39%] vs. 6% [3%-10%], P < .001), a higher rate of refractoriness to second-line therapy (16/33 [48%] vs. 13/57 [23%], P = .01), and a lower OS (5-year OS probability 38% [95% CI 23%-53%] vs. 87% [82%-92%%], P < .001). In conclusion, refractoriness to ICT was seen in 15% of patients and was predicted by high-FLIPI scores, B symptoms, and elevated serum β2-micrglobulin. Immunochemotherapy-refractory patients had a worse prognosis than ICT-sensitive patients, and current treatment options for this subgroup are not satisfactory.
滤泡性淋巴瘤的特点是对免疫化疗（ICT）反应良好。然而，一小部分患者对治疗反应不佳，预后似乎更差。本研究试图确定一线ICT难治性的预测因素和预后。分析了2002年至2014年间在4家西班牙机构诊断为II至IV期滤泡性淋巴瘤并接受一线ICT治疗的所有患者。那些在一线反应评估后6个月内无反应、进展或复发的患者被视为ICT难治性。纳入了343例患者（中位年龄58岁，48%为男性），其中53例（15%）为ICT难治性。多因素分析显示，高危滤泡性淋巴瘤国际预后指数（FLIPI）评分、B症状和β2-微球蛋白升高与难治性相关，难治性、高危FLIPI评分和β2-微球蛋白与总生存期（OS）相关。与ICT敏感患者相比，ICT难治性患者组织学转化的发生率更高（5年累积发生率25%[14%-39%]对6%[3%-10%]，P<0.001），二线治疗难治率更高（16/33[48%]对13/57[23%]，P=0.01），OS更低（5年OS概率38%[95%CI 23%-53%]对87%[82%-92%]，P<0.001）。总之，15%的患者出现ICT难治性，其预测因素为高FLIPI评分、B症状和血清β2-微球蛋白升高。免疫化疗难治性患者的预后比ICT敏感患者差，目前该亚组的治疗选择并不令人满意。
