BACKGROUND Preliminary data suggest promising activity of loncastuximab tesirine in follicular lymphoma, and synergistic activity between rituximab-induced cytotoxicity and loncastuximab tesirine. In this study, we evaluated loncastuximab tesirine combined with rituximab for second-line and later treatment of follicular lymphoma. METHODS We did a single-arm, investigator-initiated, phase 2 trial at Sylvester Comprehensive Cancer Center in Miami, FL, USA. We recruited patients aged 18 years or older with histologically confirmed relapsed or refractory follicular lymphoma (grade 1-3A) treated with one or more lines of therapy and presenting with progression or relapse of disease within 24 months (POD24) after the first line of treatment, one or more Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria, or second relapse, and with an Eastern Cooperative Oncology Group performance status of 0-2. Intravenous loncastuximab tesirine was administered on day 1 of a 21-day cycle, at 0·15 mg/kg for two cycles, then 0·075 mg/kg thereafter. Intravenous rituximab was administered on day 1 of cycle 1, at 375 mg/m2 for four once-weekly doses, followed by one dose every 8 weeks on cycles 5, 6, and 7. At week 21, patients with a complete response discontinued loncastuximab tesirine and received two more doses of rituximab once every 8 weeks. Patients with a partial response at week 21 continued both agents for 18 more weeks. The primary endpoint was complete response rate at week 12 assessed by the Lugano 2014 classification in patients who had received at least three doses of loncastuximab tesirine. The safety analysis included all patients who received one or more doses of loncastuximab tesirine. The trial is registered with ClinicalTrials.gov, NCT04998669, and is ongoing (open to recruitment); the data cutoff for this analysis was Sept 13, 2024. FINDINGS Between Jan 28, 2022, and June 3, 2024, we enrolled 39 patients (median age 68 years [IQR 58-77]; 21 [54%] male patients and 18 [46%] female patients). All patients presented with one or more GELF criteria (n=36 [92%]) or POD24 after the first line of treatment (n=20 [51%]) at baseline. As of Sept 13, 2024, the median follow-up was 18·2 months (95% CI 12·0-19·3). Week 12 complete response rate was 67% (n=26 of 39). The most common grade 3 or worse treatment-emergent adverse events (TEAEs) were lymphopenia (eight [21%] of 39 patients) and neutropenia (five [13%] patients; one of whom had a serious grade 3 TEAE of febrile neutropenia that was considered to be related to study treatment). Generalised and peripheral oedema was predominantly grade 1-2 and all cases of oedema were treatable with diuretics. Serious TEAEs that were considered to be related to study drugs occurred in four (10%) of 39 patients. No fatal TEAEs occurred. INTERPRETATION Loncastuximab tesirine with rituximab showed clinically meaningful activity in relapsed or refractory follicular lymphoma, and had a manageable safety profile. FUNDING ADC Therapeutics and Sylvester Comprehensive Cancer Center.

中文翻译：

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Loncastuximab tesirine 联合利妥昔单抗治疗复发或难治性滤泡性淋巴瘤患者：一项单中心、单臂、2 期试验。


背景初步数据表明 loncastuximab tesirine 在滤泡性淋巴瘤中的活性很有希望，以及利妥昔单抗诱导的细胞毒性与 loncastuximab tesirine 之间的协同活性。在这项研究中，我们评估了 loncastuximab tesirine 联合利妥昔单抗用于滤泡性淋巴瘤的二线和后续治疗。方法 我们在美国佛罗里达州迈阿密的 Sylvester 综合癌症中心进行了一项单臂、研究者发起的 2 期试验。我们招募了 18 岁或以上的患者，这些患者患有经组织学证实的复发或难治性滤泡性淋巴瘤（1-3A 级），接受一种或多种治疗，并在一线治疗后 24 个月内 （POD24） 出现疾病进展或复发，一种或多项 Groupe d'Etude des Lymphomes 毛囊炎 （GELF） 标准，或第二次复发， 并且 Eastern Cooperative Oncology Group 表现状态为 0-2。静脉注射 loncastuximab tesirine 在 21 天周期的第 1 天给药，以 0·15 mg/kg 持续两个周期，然后以 0·075 mg/kg 给药。静脉注射利妥昔单抗在第 1 周期的第 1 天给药，剂量为 375 mg/m2，每周给药 4 次，随后在第 5、6 和 7 周期每 8 周给药 1 剂。在第 21 周，完全反应的患者停用 loncastuximab tesirine，并每 8 周一次再接受两剂利妥昔单抗。第 21 周时部分缓解的患者继续两种药物 18 周。主要终点是第 12 周的完全缓解率，根据 Lugano 2014 分类评估了接受至少 3 剂 loncastuximab tesirine 的患者。安全性分析包括所有接受一剂或多剂 loncastuximab tesirine 的患者。该试验已在 ClinicalTrials 注册。gov、NCT04998669 和 is running（开放招聘）;该分析的数据截止日期为 2024 年 9 月 13 日。结果在 2022 年 1 月 28 日至 2024 年 6 月 3 日期间，我们招募了 39 名患者 （中位年龄 68 岁 [IQR 58-77];21 名 [54%] 男性患者和 18 名 [46%] 女性患者）。所有患者在基线时在一线治疗后出现一个或多个 GELF 标准 （n=36 [92%]） 或 POD24 （n=20 [51%]）。截至 2024 年 9 月 13 日，中位随访时间为 18·2 个月 （95% CI 12·0-19·3）。第 12 周完全缓解率为 67% （n=26/39）。最常见的 3 级或更严重的治疗中出现的不良事件 （TEAE） 是淋巴细胞减少症（39 名患者中有 8 名 [21%]）和中性粒细胞减少症（5 名 [13%] 患者;其中一名患者患有严重的 3 级发热性中性粒细胞减少症 TEAE，被认为与研究治疗有关）。全身性和外周性水肿主要为 1-2 级，所有水肿病例均可使用利尿剂治疗。被认为与研究药物相关的严重 TEAE 发生在 39 例患者中的 4 例 （10%） 中。未发生致命的 TEAE。解释 Loncastuximab tesirine 联合利妥昔单抗在复发或难治性滤泡性淋巴瘤中显示出具有临床意义的活性，并且具有可控的安全性。资助 ADC Therapeutics 和 Sylvester 综合癌症中心。