Tafasitamab, lenalidomide, and rituximab in relapsed or refractory follicular lymphoma (inMIND): a global, phase 3, randomised controlled trial.

Lenalidomide plus rituximab is a commonly used immunotherapy combination in patients with relapsed or refractory follicular lymphoma.

在复发或难治性滤泡性淋巴瘤患者中，来那度胺联合利妥昔单抗是一种常用的免疫治疗组合。

We aimed to assess the efficacy and safety of adding tafasitamab, a CD19-targeted Fc-enhanced monoclonal antibody, to lenalidomide and rituximab in this setting.

我们旨在评估将靶向CD19的Fc增强型单克隆抗体tafasitamab添加到来那度胺和利妥昔单抗中的疗效和安全性。

Methods

This phase 3, double-blind, randomised, placebo-controlledtrial (inMIND) was done in 210 centres (including community-based haematology clinics, major hospitals, and academic institutions) in North America, Europe, and the Asia-Pacific region.

这项第三阶段、双盲、随机、安慰剂对照试验（inMIND）在美国、欧洲和亚太地区的210个中心（包括社区血液科诊所、主要医院和学术机构）进行。

Adults with relapsed or refractory follicular lymphoma, who had received at least one previous line of systemic therapy, were eligible for enrolment and randomly assigned (1:1) to receive treatment with up to 12 cycles (28-day cycle length) of tafasitamab (12 mg/kg by intravenous infusion on days 1, 8, 15, and 22 of cycles 1-3 and days 1 and 15 of cycles 4-12) or placebo, both with lenalidomide (20 mg/day orally on days 1-21 of cycles 1-12) and rituximab (375 mg/m2 by intravenous infusion on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-5).

复发或难治性滤泡性淋巴瘤的成人患者，如果之前至少接受过一种系统性治疗，就有资格入组并随机分配（1:1），接受最多12个周期（28天为一个周期长度）的tafasitamab治疗（第1-3周期的第1、8、15和22天以及第4-12周期的第1和15天通过静脉输注12 mg/kg）或安慰剂，两种治疗均与来那度胺（第1-12周期的第1-21天每天口服20 mg）和利妥昔单抗（第1周期的第1、8、15和22天以及第2-5周期的第1天通过静脉输注375 mg/m2）联合使用。

Treatment assignment was achieved via an interactive voice or web response system; patients, investigators, and the funder were masked until the primary analysis.

治疗分配是通过交互式语音或网络响应系统实现的；患者、研究人员和资助者在主要分析之前都处于盲态。

Study endpoints were investigator assessed unless otherwise specified.

除非另有说明，研究终点由研究者评估。

The primary endpoint was progression-free survivalin the intention-to-treatpopulation of all randomised patients; safety was assessed in all randomised patients who received at least one dose of study drug.

主要终点是在所有随机患者中意向治疗人群中无进展生存期；安全性评估是在所有至少接受一次研究药物治疗的随机患者中进行。

The trial is registered with ClinicalTrials.gov (NCT04680052) and EUDRA-CT (2020-004407-13) and is active but no longer enrolling.

该试验已在ClinicalTrials.gov (NCT04680052)和EUDRA-CT (2020-004407-13)注册，目前仍在进行中，但不再招募新患者。

Results

Between April 16, 2021, and Aug 10, 2023, a total of 817 patients were assessed for eligibility; 548 patients with relapsed or refractory follicular lymphoma were enrolled and randomly assigned to treatment with either tafasitamab (n=273) or placebo (n=275). 299 (55%) of all randomised patients were male and 249 (45%) were female.

2021年4月16日至2023年8月10日期间，共有817名患者接受了资格评估；其中548名复发或难治性滤泡性淋巴瘤患者被纳入研究，并随机分配接受tafasitamab治疗（n=273）或安慰剂治疗（n=275）。所有随机患者中，299名（55%）为男性，249名（45%）为女性。

The addition of tafasitamab to lenalidomide and rituximab resulted in significantly lower risk of progression, relapse, or death versus placebo (median progression-free survivalby investigator 22·4 months [95% CI 19·2 to not evaluable] in the tafasitamab group vs 13·9 months [11·5-16·4] in the placebo group; hazard ratio0·43 [95% CI 0·32-0·58]; p<0·0001) in the planned primary analysis.

将tafasitamab加入lenalidomide和rituximab治疗中，与安慰剂相比，显著降低了疾病进展、复发或死亡的风险（研究者评估的无进展生存期中位数在tafasitamab组为22.4个月[95% 置信区间 19.2至未评估]，而在安慰剂组为13.9个月[11.5-16.4]；风险比为0.43[95% 置信区间 0.32-0.58]；p<0.0001），这是计划中的主要分析结果。

Improvement in progression-free survivalwas confirmed by independent review committee.

独立审查委员会确认了无进展生存期的改善。

Adverse events were reported in 272 (99%) of 274 patients in the tafasitamab group and 270 (99%) of 272 patients in the placebo group.

在接受tafasitamab治疗的274名患者中，有272名（99%）报告了不良事件，在接受安慰剂治疗的272名患者中，有270名（99%）报告了不良事件。

Most common adverse events occurring in either the tafasitamab group or placebo group were neutropenia (133 [49%] vs 123 [45%]) and diarrhoea (103 [38%] vs 77 [28%]).

在tafasitamab组或安慰剂组中最常见的不良事件是中性粒细胞减少症（133名[49%]对比123名[45%]）和腹泻（103名[38%]对比77名[28%]）。

There were no deaths due to treatment-related adverse events in the tafasitamab group; two (1%) patients had fatal adverse events related to treatment in the placebo group.

在 tafasitamab 组中，没有患者因治疗相关不良事件死亡；在安慰剂组中，有两名（1%）患者因治疗相关的不良事件死亡。

interpretation

The addition of tafasitamab to lenalidomide and rituximab resulted in a statistically significant and clinically meaningful improvement in progression-free survival, with an acceptable safety profile in patients with relapsed or refractory follicular lymphoma.

将 tafasitamab 添加到来那度胺和利妥昔单抗中，对于复发或难治性滤泡性淋巴瘤患者，导致了无进展生存期的统计学上显著且具有临床意义的改善，且安全性可接受。

This combination represents a potential new standard-of-care treatment.

这种联合疗法代表了一种潜在的新治疗标准。

funding

Incyte.

Incyte 公司。