Early Relapse of Follicular Lymphoma after Rituximab-Based Biologic Doublet Upfront Therapy Is Associated with Increased Risk of Death: A Combined Analysis from CALGB Studies 50402, 50701 and 50803 (Alliance)
Early Relapse of Follicular Lymphoma after Rituximab-Based Biologic Doublet Upfront Therapy Is Associated with Increased Risk of Death: A Combined Analysis from CALGB Studies 50402, 50701 and 50803 (Alliance)
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基于利妥昔单抗的生物双重前期治疗后滤泡性淋巴瘤的早期复发与死亡风险增加相关：CALGB 研究 50402、50701 和 50803（联盟）的综合分析
DOI：
10.1182/blood.v128.22.2953.2953
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发表时间：
2016
期刊：
影响因子：
20.3
通讯作者：
K. Blum
中科院分区：
文献类型：
--
作者：
F. Lansigan;I. Barak;B. Pitcher;Sin;B. Cheson;M. Czuczman;B. Grant;P. Martin;E. Hsi;H. Schöder;Scott E. Smith;N. Bartlett;J. Leonard;K. Blum
背景：在接受一线 R-CHOP 治疗的滤泡性淋巴瘤 (FL) 患者中，诊断后 2 年内的早期疾病进展 (POD) 与高死亡风险（风险比 6.4）和 50% 的 5 年总生存率相关（Casulo 等人，JCO 2015）。这些观察结果是否适用于未经化疗的患者尚不清楚。肿瘤临床试验联盟开展了三项一线基于利妥昔单抗的不含化疗的生物免疫治疗双重临床试验：R-Galiximab（抗 CD80，CALGB 50402）、R-Epratuzumab（抗 CD22，CALGB 50701）和 R-来那度胺（CALGB 50803）。我们对 174 名患者进行了回顾性分析，以确定初始生物、非细胞毒性治疗后早期进展者的结果以及早期 POD 的危险因素。方法：CALGB 50402 (n=60)、CALGB 50701 (n=57) 和 CALGB 50803 (n=57) 具有相似的资格标准：既往未经治疗的滤泡性淋巴瘤，1、2 或 3a 级，伴 III、IV 期或大块（单个肿块 >7 cm）II 期疾病，ECOG PS 0 至 2。早期 POD 定义为自入学起 24 个月。使用前向选择进行单变量和多变量逻辑回归模型来识别早期 POD 的预测因子。采用Kaplan-Meier (KM)方法估计2年和5年总生存概率。使用针对 FLIPI 进行调整的单变量和多变量 Cox 回归模型计算风险比 (HR) 和 95% CI。结果：27% (48/174) 的患者出现早期 POD。从研究开始的中位生存随访时间为 5.5 年（2.1 至 10.1 年），从诊断到入组的中位时间为 2 个月（0.2 至 115 个月）。中位年龄为 54 岁（范围：22-90 岁），49% 为男性，24% 为低风险、52% 为中风险、24% 为高风险 FLIPI（表 1）。研究早期的 POD 导致 OS 较差 [HR=4.86 (95% CI 1.90-12.4)，p 单变量分析显示年龄 >60 (p=0.019)、男性 (p=0.002)、较高的 FLIPI (p=4 (p=0.010)、升高的 LDH (p=0.004)、淋巴结大小 >7 cm (p=0.002)、白蛋白结论：接受基于利妥昔单抗的一线生物非细胞毒性治疗的患者在诊断后 2 年内早期复发与死亡风险增加相关，这些数据与之前国家 LymphoCare 研究中接受 R-CHOP 治疗的患者的结果相似，表明早期 POD 患者的不良生存可能与全身治疗方式无关，以识别可能出现不良结果的患者以及哪些患者接受生物治疗。支持：U10CA180821、U10CA180882.ClinicalTrials.gov 标识符：NCT00117975 (CALGB 50402)、NCT00553501 (CALGB 50701) 和 NCT01145495 (CALGB 50803) Consultancy; Teva: Research Funding; Celgene: Consultancy; Spectrum: Consultancy, Research Funding. Cheson:Gilead: Research Funding; Pharmacyclics: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Acerta: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Czuczman:Celgene: Employment. Martin:Celgene: Consultancy, Honoraria; Janssen: Consultancy,酬金，其他：研究资助；诺华：咨询；Hsi：礼来：咨询；Cellerant Therapeutics：咨询；HTG 分子诊断：酬金。
Background: In follicular lymphoma (FL) patients treated with first-line R-CHOP, early progression of disease (POD) within 2 years after diagnosis is associated with high risk for death (hazard ratio 6.4) and a 50% 5-year overall survival (Casulo et al. JCO 2015). Whether these observations hold for patients treated without chemotherapy is unknown. The Alliance for Clinical Trials in Oncology conducted three frontline rituximab-based non-chemotherapy-containing biologic immunotherapy doublet clinical trials: R-Galiximab (Anti-CD80, CALGB 50402), R-Epratuzumab (Anti-CD22, CALGB 50701) and R-Lenalidomide (CALGB 50803). We performed a retrospective analysis of 174 patients to determine outcomes of early progressors after initial biologic, non-cytotoxic treatment and risk factors for early POD. Methods: CALGB 50402 (n=60), CALGB 50701 (n=57), and CALGB 50803 (n=57) had similar eligibility criteria: previously untreated follicular lymphoma, grade 1, 2 or 3a with stage III, IV or bulky (single mass >7 cm) stage II disease, and ECOG PS 0 to 2. Early POD was defined as progression within 24 months from study entry. Univariate and multivariate logistic regression modeling using forward selection was performed to identify predictors of early POD. Kaplan-Meier (KM) method was used to estimate 2-year and 5-year overall survival probability. Hazard ratios (HR) and 95% CI were calculated using a univariate and multivariate Cox regression model adjusting for FLIPI. Results: Twenty-seven percent (48/174) of patients had early POD. Median survival follow-up time from study entry was 5.5 years (2.1 to 10.1 years) and median time from diagnosis to enrollment was 2 months (0.2 to 115 months). Median age was 54 (range: 22-90), 49% were male and 24% had low-, 52% intermediate- and 24% high-risk FLIPI (Table 1). Early POD from study entry conferred a worse OS [HR=4.86 (95% CI 1.90-12.4), p Univariate analysis revealed age >60 (p=0.019), male sex (p=0.002), higher FLIPI (p 4 (p=0.010), elevated LDH (p=0.004), nodal size >7 cm (p=0.002), albumin Conclusions: Early relapse within 2 years after diagnosis in patients receiving front-line rituximab-based biologic non-cytotoxic therapy is associated with an increased risk of death. These data are similar to previous findings in patients treated with R-CHOP from the National LymphoCare study, suggesting that the adverse survival of patients with early POD may be independent of systemic treatment modality. Novel clinicopathological approaches are needed at diagnosis to identify patients who are likely to have unfavorable outcomes, and for whom biologic doublets are efficacious. Support: U10CA180821, U10CA180882.ClinicalTrials.gov Identifier: NCT00117975 (CALGB 50402), NCT00553501 (CALGB 50701), and NCT01145495 (CALGB 50803) Disclosures Lansigan:Pharmacyclics: Consultancy; Teva: Research Funding; Celgene: Consultancy; Spectrum: Consultancy, Research Funding. Cheson:Gilead: Research Funding; Pharmacyclics: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Acerta: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Czuczman:Celgene: Employment. Martin:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: travel, accommodations, expenses; Teva: Research Funding; Acerta: Consultancy; Novartis: Consultancy; Gilead: Consultancy, Other: travel, accommodations, expenses. Hsi:Eli Lilly: Consultancy; Abbvie: Consultancy; Cellerant Therapeutics: Consultancy; Seattle Genetics: Honoraria; HTG molecular diagnostics: Honoraria. Bartlett:Gilead: Consultancy.