Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, and patients with low-risk disease after initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD. Eligible patients were adults with newly diagnosed CD20 B-cell PTLD after solid organ transplant and performance status 0 to 2. Initial treatment comprised 49 days of ibrutinib 560 mg once daily, with 4 doses of weekly rituximab. Treatment response on interim scan and baseline International Prognostic Index were used to allocate patients to either a low-risk arm (who continued ibrutinib, alongside 4 further doses of 3-weekly rituximab) or high-risk (escalation to R-CHOP immunochemotherapy, with ibrutinib continuing in patients aged <65 years). The primary outcome was complete response on interim scan, achieved by 11 of 38 patients (29%; 95% confidence interval [CI], 15-46). This did not reach the prespecified threshold for clinically significant activity. Secondary outcomes included allocation to the low-risk arm (41% of patients), 2-year progression-free survival (58%; 95% CI, 44-76), and 2-year overall survival (76%; 95% CI, 63-91). Adverse events were mostly hematological, gastrointestinal, and infective. Although TIDaL does not support adding ibrutinib into first-line treatment of PTLD, increasing the proportion of patients who can be treated without cytotoxic chemotherapy remains an important aim of future research. This trial was registered at as # ISRCTN32667607.

中文翻译：

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依鲁替尼作为移植后淋巴增殖性疾病风险分层治疗的一部分：2 期 TIDaL 试验

移植后淋巴增殖性疾病（PTLD）是实体器官移植的罕见并发症，细胞毒性化疗与治疗相关的发病率和死亡率相关。目前的治疗采用序贯、风险分层的方法，初始免疫治疗后患有低风险疾病的患者可以避免升级为免疫化疗。 TIDaL 是一项前瞻性、单组 2 期试验，研究依鲁替尼联合风险分层疗法一线治疗 PTLD 的活性和耐受性。符合条件的患者是实体器官移植后新诊断的 CD20 B 细胞 PTLD 且体力状态为 0 至 2 的成人。初始治疗包括 49 天的依鲁替尼 560 毫克每天一次，每周 4 剂利妥昔单抗。中期扫描的治疗反应和基线国际预后指数用于将患者分配至低风险组（继续使用依鲁替尼，同时每 3 周再接受 4 剂利妥昔单抗）或高风险组（升级至 R-CHOP 免疫化疗，依鲁替尼继续用于年龄 <65 岁的患者）。主要结局是中期扫描完全缓解，38 名患者中有 11 名达到完全缓解（29%；95% 置信区间 [CI]，15-46）。这没有达到临床显着活性的预定阈值。次要结局包括分配至低风险组（41% 的患者）、2 年无进展生存期（58%；95% CI，44-76）和 2 年总生存期（76%；95% CI） ，63-91）。不良事件主要是血液学、胃肠道和感染性事件。尽管TIDaL不支持将依鲁替尼添加到PTLD一线治疗中，但增加无需细胞毒性化疗即可治疗的患者比例仍然是未来研究的重要目标。该试验注册号为#ISRCTN32667607。