Department of Medicine, Wilmot Cancer Institute, University of Rochester, Rochester, NY, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Lancet Haematol. 2022 Apr;9(4):e289-e300. doi: 10.1016/S2352-3026(22)00033-3.
Novel therapies for relapsed or refractory follicular lymphoma are commonly evaluated in single-arm studies without formal comparison with other treatments or historical controls. Consequently, rigorously defined treatment outcomes informing expectations for novel therapeutic strategies in this population are sparse. To inform outcome expectations, we aimed to describe treatment patterns, survival outcomes, and duration of response in patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy.
In this multicentre cohort study, we developed a database of patients with relapsed or refractory follicular lymphoma from eight academic centres in the USA using data collected in the LEO Cohort study (NCT02736357) and the LEO Consortium. For this analysis, eligible patients were aged at least 18 years, had non-transformed grade 1-3a follicular lymphoma, and were receiving systemic therapy in the third line or later after previous therapy with an anti-CD20 antibody and an alkylating agent. Clinical data and patient outcomes were abstracted from medical records by use of a standard protocol. The index therapy for the primary analysis was defined as the first line of systemic therapy after the patient had received at least two previous systemic therapies that included an alkylating agent and an anti-CD20 therapy. The main endpoints of interest were overall response rate, progression-free survival, and overall survival. Outcomes were also evaluated in subsets of clinical interest (index therapy characteristics, patient and disease characteristics, treatment history, and best response assessment).
We screened 933 patients with follicular lymphoma, of whom 441 were included and diagnosed between March 6, 2002, and July 20, 2018. Index therapies included immunochemotherapy (n=133), anti-CD20 antibody monotherapy (n=53), lenalidomide with or without anti-CD20 (n=37), and phosphoinositide 3-kinase inhibitors with or without anti-CD20 (n=25). 57 (13%) of 441 patients received haematopoietic stem-cell transplantation and 98 (23%) of 421 patients with complete data received therapy on clinical trials. After a median follow-up of 71 months (IQR 64-79) from index therapy, 5-year overall survival was 75% (95% CI 70-79), median progression-free survival was 17 months (15-19), and the overall response rate was 70% (65-74; 280 of 400 patients evaluable for response). Patients who were refractory to therapy with an alkylating agent had a lower overall response rate (170 [68%] of 251 patients vs 107 [77%] of 139 patients) and a significantly lower 5-year overall survival (72%, 95% CI 66-78 vs 81%, 73-89; hazard ratio 1·60, 95% CI 1·04-2·46) than patients who were not refractory to therapy with an alkylating agent.
Patients with relapsed or refractory follicular lymphoma receive heterogeneous treatments in the third-line setting or later. We observed high response rates to contemporary therapies that were of short duration. These data identify unmet needs among patients with follicular lymphoma, especially those who are refractory to alkylating agents, and might provide evidence by which clinical trials evaluating novel treatments could be assessed.
Genentech and the National Cancer Institute.
新型疗法常用于治疗复发/难治性滤泡性淋巴瘤，通常在无其他治疗方法或历史对照的情况下进行单臂研究。因此，关于该人群中新型治疗策略的严格定义的治疗结果信息非常有限。为了提供预后信息，我们旨在描述接受三线或三线以上系统治疗的复发/难治性滤泡性淋巴瘤患者的治疗模式、生存结局和缓解持续时间。
在这项多中心队列研究中，我们使用来自美国 8 个学术中心的 LEO 队列研究（NCT02736357）和 LEO 联盟的数据，建立了一个复发/难治性滤泡性淋巴瘤患者的数据库。对于本分析，符合条件的患者年龄至少为 18 岁，患有非转化的 1-3a 级滤泡性淋巴瘤，在接受抗 CD20 抗体和烷化剂的至少两次先前治疗后，正在接受三线或三线以上的系统治疗。临床数据和患者结局通过使用标准方案从病历中提取。主要分析的索引治疗定义为患者接受至少两次包含烷化剂和抗 CD20 治疗的先前系统治疗后的一线系统治疗。主要关注的结局是总缓解率、无进展生存期和总生存期。在具有临床意义的亚组（索引治疗特征、患者和疾病特征、治疗史和最佳反应评估）中也评估了结局。
我们筛选了 933 名滤泡性淋巴瘤患者，其中 441 名被纳入并在 2002 年 3 月 6 日至 2018 年 7 月 20 日之间确诊。索引治疗包括免疫化疗（n=133）、抗 CD20 抗体单药治疗（n=53）、来那度胺联合或不联合抗 CD20（n=37）和磷酸肌醇 3-激酶抑制剂联合或不联合抗 CD20（n=25）。57 名（13%）患者接受了造血干细胞移植，98 名（23%）有完整数据的患者接受了临床试验治疗。从索引治疗开始，中位随访 71 个月（IQR 64-79）后，5 年总生存率为 75%（95%CI 70-79），中位无进展生存期为 17 个月（15-19），总缓解率为 70%（65-74；280 名可评估反应的患者中有 107 名）。对烷化剂治疗耐药的患者总缓解率较低（251 名患者中 170 名[68%]，139 名患者中 107 名[77%]），5 年总生存率明显较低（72%，95%CI 66-78 与 81%，73-89；风险比 1.60，95%CI 1.04-2.46）。
复发/难治性滤泡性淋巴瘤患者在三线或更晚的治疗中接受了多种治疗方法。我们观察到，对当代治疗方法的缓解率很高，但缓解持续时间较短。这些数据确定了滤泡性淋巴瘤患者的未满足需求，特别是那些对烷化剂耐药的患者，这些数据可能为评估新型治疗方法的临床试验提供证据。
复发/难治性滤泡性淋巴瘤患者在三线或更晚的治疗中接受了多种治疗方法。我们观察到对当代治疗方法的缓解率较高，但缓解持续时间较短。这些数据确定了滤泡性淋巴瘤患者的未满足需求，特别是那些对烷化剂耐药的患者，这些数据可能为评估新型治疗方法的临床试验提供证据。
罗氏和美国国家癌症研究所。
