Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial,The Lancet

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Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial
The Lancet ( IF 98.4 ) Pub Date : 2024-11-14 , DOI: 10.1016/s0140-6736(24)01774-4
Jeremy S Abramson, Matthew Ku, Mark Hertzberg, Hui-Qiang Huang, Christopher P Fox, Huilai Zhang, Dok Hyun Yoon, Won-Seog Kim, Haifaa Abdulhaq, William Townsend, Charles Herbaux, Jan M Zaucha, Qing-Yuan Zhang, Hung Chang, Yanyan Liu, Chan Yoon Cheah, Herve Ghesquieres, Stephen Simko, Victor Orellana-Noia, Richard Ta, Gareth P Gregory

Background

Glofitamab monotherapy induces durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma after two or more previous therapies, but has not previously been assessed as a second-line therapy. We investigated the efficacy and safety of glofitamab plus gemcitabine–oxaliplatin (Glofit-GemOx) versus rituximab (R)-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma.

Methods

The phase 3, randomised, open-label STARGLO trial was done at 62 centres in 13 countries in Asia and Australia, Europe, and North America. We recruited transplant-ineligible patients (aged ≥18 years) with histologically confirmed relapsed or refractory diffuse large B-cell lymphoma after one or more previous therapies. Patients were randomly assigned in permuted blocks (block size of six) via an interactive voice or web response system (2:1; stratified by 1 vs ≥2 previous lines of therapy and relapsed vs refractory status) to Glofit-GemOx (intravenous gemcitabine 1000 mg/m² and oxaliplatin 100 mg/m² plus glofitamab step-up dosing to 30 mg; for a total of eight cycles, plus four additional cycles of glofitamab monotherapy) or R-GemOx (intravenous gemcitabine 1000 mg/m² and oxaliplatin 100 mg/m² plus rituximab 375 mg/m²; for a total of eight cycles). The trial independent review committee, which evaluated all response-based endpoints, was masked to treatment assignment. The primary endpoint was overall survival. Efficacy analyses were by intention to treat in all randomly assigned patients. We present results from both the primary analysis (cutoff: March 29, 2023) and updated analysis after all patients had completed study therapy (cutoff: Feb 16, 2024). Safety analyses included all patients who received any study treatment. This study is registered with ClinicalTrials.gov, NCT04408638, and is ongoing (closed to recruitment).

Findings

From Feb 23, 2021, to March 14, 2023, 274 patients were enrolled and randomly assigned to receive Glofit-GemOx (n=183) or R-GemOx (n=91). 158 (58%) patients were male and 116 (42%) were female; median age was 68 years (IQR 58–74). At the primary analysis after a median follow-up of 11·3 months (95% CI 9·6–12·7), overall survival was significantly improved with Glofit-GemOx versus R-GemOx (median not estimable [NE; 95% CI 13·8 months–NE] vs 9·0 months [7·3–14·4]; hazard ratio [HR] 0·59 [95% CI 0·40–0·89]; p=0·011). At the updated analysis after a median follow-up of 20·7 months (19·9–23·3), a consistent improvement in overall survival was observed with Glofit-GemOx versus R-GemOx (median 25·5 months [18·3–NE] vs 12·9 months [7·9–18·5]; HR 0·62 [0·43–0·88]). In the safety sets, 180 (100%) patients in the Glofit-GemOx group and 84 (96%) of 88 patients in the R-GemOx group had at least one adverse event during the study period. Cytokine release syndrome occurred in 76 (44%) of 172 glofitamab-exposed patients and was predominantly low grade. Deaths related to glofitamab or rituximab occurred in five (3%) patients in the Glofit-GemOx group and in one (1%) patient in the R-GemOx group.

Interpretation

Glofit-GemOx had a significant overall survival benefit compared with R-GemOx, supporting its use in transplant-ineligible patients with relapsed or refractory diffuse large B-cell lymphoma after one or more previous lines of therapy.

Funding

F Hoffmann-La Roche.

中文翻译：

Glofitamab 联合吉西他滨和奥沙利铂（GemOx）与利妥昔单抗-GemOx 治疗复发或难治性弥漫性大 B 细胞淋巴瘤（STARGLO）：一项全球 3 期、随机、开放标签试验

背景

Glofitamab 单药治疗可诱导既往 2 次或多种治疗后复发或难治性弥漫性大 B 细胞淋巴瘤患者的持久缓解，但之前未被评估为二线治疗。我们研究了 glofitamab 联合吉西他滨-奥沙利铂（Glofit-GemOx）与利妥昔单抗（R）-GemOx 在复发或难治性弥漫性大 B 细胞淋巴瘤患者中的疗效和安全性。

方法

3 期、随机、开放标签 STARGLO 试验在亚洲、澳大利亚、欧洲和北美 13 个国家的 62 个中心进行。我们招募了不适合移植的患者（年龄 ≥18 岁），这些患者在一种或多种既往治疗后经组织学证实为复发或难治性弥漫性大 B 细胞淋巴瘤。通过交互式语音或网络响应系统（2：1;按 1 线与 ≥2 线既往治疗和复发与难治状态分层）将患者随机分配到 Glofit-GemOx（静脉注射吉西他滨 1000 mg/m² 和奥沙利铂 100 mg/m² 加 glofitamab 升压给药至 30 mg;总共八个周期，加上四个额外的 glofitamab 单药治疗周期）或 R-GemOx（静脉注射吉西他滨 1000 mg/m² 和奥沙利铂 100 mg/m² 加利妥昔单抗 375 mg/m²;总共八个周期）。评估所有基于反应的终点的试验独立审查委员会对治疗分配不设盲。主要终点是总生存期。疗效分析按意向治疗对所有随机分配的患者进行。我们展示了主要分析（截止日期：2023 年 3 月 29 日）和所有患者完成研究治疗后的最新分析（截止日期：2024 年 2 月 16 日）的结果。安全性分析包括所有接受任何研究治疗的患者。这项研究已在 ClinicalTrials.gov， NCT04408638 注册，并且正在进行中（已停止招募）。

发现

从 2021 年 2 月 23 日至 2023 年 3 月 14 日，共招募了 274 例患者，并随机分配接受 Glofit-GemOx （n=183）或 R-GemOx （n=91）。158 例（58%）患者为男性，116 例（42%）为女性;中位年龄为 68 岁（IQR 58-74）。在中位随访 11·3 个月后的初步分析中（95% CI 9·6–12·7），Glofit-GemOx 与 R-GemOx 相比，总生存期显著改善（中位不可估计 [NE;95% CI 13·8 个月–NE] vs 9·0 个月 [7·3–14·4];风险比 [HR] 0·59 [95% CI 0·40–0·89];p=0·011）。在中位随访 20·7 个月（19·9–23·3）后的更新分析中，观察到 Glofit-GemOx 与 R-GemOx 的总生存期持续改善（中位 25·5 个月 [18·3–NE] vs 12·9 个月 [7·9–18·5];HR 0·62 [0·43–0·88]）。在安全组中，Glofit-GemOx 组的 180 名（100%）患者和 R-GemOx 组 88 名患者中的 84 名（96%）在研究期间至少发生了一次不良事件。细胞因子释放综合征发生在 172 例 glofitamab 暴露患者中的 76 例（44%）中，并且主要是低级别。与 glofitamab 或利妥昔单抗相关的死亡发生在 Glofit-GemOx 组的 5 例（3%）患者和 R-GemOx 组的 1 例（1%）患者中。