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格非他单抗联合吉西他滨和奥沙利铂治疗复发/难治（R/R）弥漫性大b细胞淋巴瘤（DLBCL）： STARGLO的2年随访

IF 3.9 4区医学 Q2 HEMATOLOGY

Hematological Oncology Pub Date : 2025-06-16 DOI:10.1002/hon.70093_76

J. S. Abramson, M. Ku, M. Hertzberg, C. P. Fox, C. Herbaux, H. Huang, D. H. Yoon, W. S. Kim, H. Zhang, H. Abdulhaq, W. Townsend, E. Mulvihill, V. Orellana-Noia, R. Ta, H. Huang, M. J. Kallemeijn, A. Belousov, A. Bottos, L. Lundberg, G. P. Gregory

{"title":"格非他单抗联合吉西他滨和奥沙利铂治疗复发/难治（R/R）弥漫性大b细胞淋巴瘤（DLBCL）： STARGLO的2年随访","authors":"J. S. Abramson, M. Ku, M. Hertzberg, C. P. Fox, C. Herbaux, H. Huang, D. H. Yoon, W. S. Kim, H. Zhang, H. Abdulhaq, W. Townsend, E. Mulvihill, V. Orellana-Noia, R. Ta, H. Huang, M. J. Kallemeijn, A. Belousov, A. Bottos, L. Lundberg, G. P. Gregory","doi":"10.1002/hon.70093_76","DOIUrl":null,"url":null,"abstract":"Introduction: Glofitamab, a CD20:CD3 bispecific antibody, has shown durable responses as fixed duration monotherapy in R/R DLBCL after ≥ 2 prior lines of therapy (LOT; Dickinson et al. NEJM 2022). In the Phase 3 STARGLO trial, Glofit-GemOx demonstrated overall survival (OS) and progression-free survival (PFS) benefits over rituximab (R)-GemOx in autologous stem cell transplant (ASCT)-ineligible R/R DLBCL (Abramson et al. Lancet 2024). Here, we present updated efficacy and safety from the STARGLO trial (NCT04408638), including landmark analyses of patients (pts) in complete remission (CR).Methods: Pts were randomized 2:1 to receive Glofit-GemOx (8 cycles plus 4 cycles glofitamab monotherapy) or R-GemOx (8 cycles) and stratified by number of prior LOT (1 vs. ≥ 2) and refractoriness to their last therapy. After obinutuzumab pretreatment, glofitamab was given in Cycle (C) 1 as weekly step-up doses (2.5/10 mg) then 30 mg target dose every 21 days from C2 Day 1. Pts with only 1 prior LOT must have been ASCT-ineligible. Primary endpoint was OS. Secondary endpoints included independent review committee (IRC)-assessed PFS and CR rate. A landmark analysis of pts in CR at end of treatment (EOT) was performed.Results: Of 274 pts (Glofit-GemOx, n = 183; R-GemOx, n = 91), 172 (62.8%) had 1 prior LOT, 102 (37.2%) had ≥ 2 prior LOT, 153 (55.8%) were primary refractory, and 166 (60.6%) were refractory to their last therapy. Baseline characteristics were unchanged compared with the primary analysis and well balanced across arms.With 2 years (yrs) of follow-up (data cut off: June 17, 2024; median follow-up: 24.7 months [mo]), Glofit-GemOx continued to confer superior OS (median: not evaluable [NE] vs. 13.5 mo; hazard ratio [HR] 0.60, 95% confidence interval [CI]: 0.42–0.85), median IRC-assessed PFS (13.8 vs. 3.6 mo; HR 0.41, 95% CI: 0.29–0.58), and CR rate (58.5 vs. 25.3%) versus R-GemOx. For Glofit-GemOx-treated pts in CR (n = 107), median duration of CR was not reached (95% CI: 27.2–NE; median CR follow-up, 18.2 mo [range: 15.2–19.3]). In pts with a CR at EOT (n = 82), the OS and PFS rates 1 yr after EOT were 89.3% and 82.4%, respectively.The Glofit-GemOx safety profile was unchanged. Cytokine release syndrome (CRS) was the most common adverse event in glofitamab-exposed pts (Grade [Gr] 1, 32.0%; Gr 2, 10.5%; Gr 3, 2.3%). Events consistent with immune effector cell-associated neurotoxicity syndrome occurred in 4 pts (all concurrent with CRS; most Gr 1–2 [n = 3]). Exploratory biomarker and immune recovery data will be presented.Conclusions: With 2 yrs of follow-up, Glofit-GemOx sustained a clinically meaningful benefit in OS and PFS versus R-GemOx in ASCT-ineligible pts with R/R DLBCL, with most (82%) pts in CR at EOT still in remission. The safety profile was consistent with known risks of each drug. The updated analyses demonstrate durable remissions and maintained OS benefit in pts with R/R DLBCL treated with fixed duration Glofit-GemOx.Research funding declaration: STARGLO (GO41944) is sponsored by F. Hoffmann-La Roche Ltd. Third-party editorial assistance, under the direction of all authors, was provided by Roisin Weaver, MSc, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.Encore Abstract: © 2025 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the ASCO 2025 Annual Meeting. All rights reserved.Keywords: aggressive B-cell non-Hodgkin lymphoma; immunotherapyPotential sources of conflict of interest:J. S. AbramsonConsultant or advisory role: Celgene, Novartis, Abbvie, Kite (a Gilead company), EMD Serono, MorphoSys, Alimera Sciences, Karyopharm Therapeutics, Bristol-Myers Squibb, C4 Therapeutics, BeiGene, AstraZeneca, Incyte, Bluebird Bio, Kymera, Epizyme, Genmab, MustangBio, Ono Pharmaceutical, Century Therapeutics, Lilly, Caribou Biosciences, Janssen, Takeda, Interius Biotherapeutics, Cellectar, Seagen, Roche/Genentech, ADC Therapeutics, Foresight Diagnostics.Honoraria: Regeneron, AstraZeneca, Janssen, Bristol-Myers Squibb/Celgene, Abbvie, Kite (a Gilead company).Other remuneration: Research funding: Seagen, Bristol-Myers Squibb/Celgene, Cellectis, MustangBio, Regeneron, Merck.M. KuConsultant or advisory role: Roche, AbbVie.Other remuneration: Research funding: Roche, BeiGene.M. HertzbergConsultant or advisory role: Roche, Gildead.Honoraria: Pfizer, Takeda, Janssen.C. P. FoxConsultant or advisory role: AbbVie, Arvinas, BMS, GenMab, Gilead/Kite, Incyte, Morphosys, Ono, Roche, SERB, SOBI.Honoraria: AbbVie, Gilead/Kite, Incyte, Roche, SERB.Other remuneration: Speaker's bureau: AbbVie, Roche, Kite/Gilead. Research funding: AbbVie, BeiGene, Genmab, Incyte, Roche.C. HerbauxConsultant or advisory role: Roche, Janssen, Abbvie, Gilead/Kite, Incyte, Novartis.Honoraria: Roche, Janssen, Abbvie, Gilead/Kite, Incyte, Novartis.Educational grants: Roche, Janssen, Abbvie, Gilead/Kite, Incyte, Novartis.Other remuneration: Research funding: AbbVie, Takeda.D. H. YoonConsultant or advisory role: Roche, Janssen, Amgen, Celgene, Novartis, ABclonal, GI cell, Pharos iBio.Honoraria: Roche, Janssen, Celgene, Kirin Pharmaceuticals, Takeda.Other remuneration: Research funding (self): Samyung, Roche/Genentech, Janssen Oncology, Boryung. Research funding (institution): Celltrion.W. S. KimOther remuneration: Research funding: Sanofi, Beigene, Boryong, Roche, Kyowa-Kirin, Donga.H. AbdulhaqConsultant or advisory role: Novartis, BMS, Genentech, Inc., AbbVie, ADC therapeutics, Pfizer.Honoraria: Novartis, BMS, Genentech, Inc., AbbVie, ADC therapeutics, Pfizer.Educational grants: AbbVie, Genentech, Inc., Actrotech, AstraZeneca.Other remuneration: Speaker's bureau: Genentech, Inc., Alexion. Research funding: Novartis, BMS, Acrotech, ADC therapeutics, Genentech, Inc., Pfizer.W. TownsendConsultant or advisory role: Roche, Abbvie, Kite, Sobi.Honoraria: Roche, Abbvie, Kite, Sobi.Educational grants: Roche, AbbVie.Other remuneration: Research funding (institution): University College London (UCL). My institution (UCL) has received research funding from Roche for conduct of a clinical trial.E. MulvihillEmployment or leadership position: F. Hoffmann-La Roche Ltd.Stock ownership: F. Hoffmann-La Roche Ltd.Educational grants: F. Hoffmann-La Roche Ltd.V. Orellana-NoiaEmployment or leadership position: Genentech, Inc.Stock ownership: Genentech, Inc. (Roche).R. TaEmployment or leadership position: Genentech, Inc.Stock ownership: F. Hoffmann-La Roche.Educational grants: Genentech, Inc.Other remuneration: Research funding: Genentech, Inc. (salaried employee).H. HuangEmployment or leadership position: F. Hoffmann-La Roche Ltd.Other remuneration: Patents, royalties, other intellectual property: F. Hoffmann-La Roche Ltd.M. J. KallemeijnEmployment or leadership position: F. Hoffmann-La Roche Ltd.A. BelousovEmployment or leadership position: F. Hoffmann-La Roche Ltd.Stock ownership: F. Hoffmann-La Roche Ltd.Educational grants: F. Hoffmann-La Roche Ltd.A. BottosEmployment or leadership position: F. Hoffmann-La Roche Ltd.Stock ownership: F. Hoffmann-La Roche Ltd.L. LundbergEmployment or leadership position: F. Hoffmann-La Roche Ltd.Stock ownership: F. Hoffmann-La Roche Ltd.Other remuneration: Patents, royalties, other intellectual property: F. Hoffmann-La Roche Ltd.G. P. GregoryConsultant or advisory role: Roche/Genentech, BMS, Gilead/Kite, Prelude Therapeutics, Clinigen, Merck.Educational grants: Novartis.Other remuneration: Speaker's bureau: Roche/Genentech. Research funding: BeiGene, Merck.","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_76","citationCount":"0","resultStr":"{\"title\":\"GLOFITAMAB PLUS GEMCITABINE AND OXALIPLATIN (Glofit-GemOx) IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): 2-YEAR FOLLOW-UP OF STARGLO\",\"authors\":\"J. S. Abramson, M. Ku, M. Hertzberg, C. P. Fox, C. Herbaux, H. Huang, D. H. Yoon, W. S. Kim, H. Zhang, H. Abdulhaq, W. Townsend, E. Mulvihill, V. Orellana-Noia, R. Ta, H. Huang, M. J. Kallemeijn, A. Belousov, A. Bottos, L. Lundberg, G. P. Gregory\",\"doi\":\"10.1002/hon.70093_76\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Introduction: Glofitamab, a CD20:CD3 bispecific antibody, has shown durable responses as fixed duration monotherapy in R/R DLBCL after ≥ 2 prior lines of therapy (LOT; Dickinson et al. NEJM 2022). In the Phase 3 STARGLO trial, Glofit-GemOx demonstrated overall survival (OS) and progression-free survival (PFS) benefits over rituximab (R)-GemOx in autologous stem cell transplant (ASCT)-ineligible R/R DLBCL (Abramson et al. Lancet 2024). Here, we present updated efficacy and safety from the STARGLO trial (NCT04408638), including landmark analyses of patients (pts) in complete remission (CR).Methods: Pts were randomized 2:1 to receive Glofit-GemOx (8 cycles plus 4 cycles glofitamab monotherapy) or R-GemOx (8 cycles) and stratified by number of prior LOT (1 vs. ≥ 2) and refractoriness to their last therapy. After obinutuzumab pretreatment, glofitamab was given in Cycle (C) 1 as weekly step-up doses (2.5/10 mg) then 30 mg target dose every 21 days from C2 Day 1. Pts with only 1 prior LOT must have been ASCT-ineligible. Primary endpoint was OS. Secondary endpoints included independent review committee (IRC)-assessed PFS and CR rate. A landmark analysis of pts in CR at end of treatment (EOT) was performed.Results: Of 274 pts (Glofit-GemOx, n = 183; R-GemOx, n = 91), 172 (62.8%) had 1 prior LOT, 102 (37.2%) had ≥ 2 prior LOT, 153 (55.8%) were primary refractory, and 166 (60.6%) were refractory to their last therapy. Baseline characteristics were unchanged compared with the primary analysis and well balanced across arms.With 2 years (yrs) of follow-up (data cut off: June 17, 2024; median follow-up: 24.7 months [mo]), Glofit-GemOx continued to confer superior OS (median: not evaluable [NE] vs. 13.5 mo; hazard ratio [HR] 0.60, 95% confidence interval [CI]: 0.42–0.85), median IRC-assessed PFS (13.8 vs. 3.6 mo; HR 0.41, 95% CI: 0.29–0.58), and CR rate (58.5 vs. 25.3%) versus R-GemOx. For Glofit-GemOx-treated pts in CR (n = 107), median duration of CR was not reached (95% CI: 27.2–NE; median CR follow-up, 18.2 mo [range: 15.2–19.3]). In pts with a CR at EOT (n = 82), the OS and PFS rates 1 yr after EOT were 89.3% and 82.4%, respectively.The Glofit-GemOx safety profile was unchanged. Cytokine release syndrome (CRS) was the most common adverse event in glofitamab-exposed pts (Grade [Gr] 1, 32.0%; Gr 2, 10.5%; Gr 3, 2.3%). Events consistent with immune effector cell-associated neurotoxicity syndrome occurred in 4 pts (all concurrent with CRS; most Gr 1–2 [n = 3]). Exploratory biomarker and immune recovery data will be presented.Conclusions: With 2 yrs of follow-up, Glofit-GemOx sustained a clinically meaningful benefit in OS and PFS versus R-GemOx in ASCT-ineligible pts with R/R DLBCL, with most (82%) pts in CR at EOT still in remission. The safety profile was consistent with known risks of each drug. The updated analyses demonstrate durable remissions and maintained OS benefit in pts with R/R DLBCL treated with fixed duration Glofit-GemOx.Research funding declaration: STARGLO (GO41944) is sponsored by F. Hoffmann-La Roche Ltd. Third-party editorial assistance, under the direction of all authors, was provided by Roisin Weaver, MSc, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.Encore Abstract: © 2025 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the ASCO 2025 Annual Meeting. All rights reserved.Keywords: aggressive B-cell non-Hodgkin lymphoma; immunotherapyPotential sources of conflict of interest:J. S. AbramsonConsultant or advisory role: Celgene, Novartis, Abbvie, Kite (a Gilead company), EMD Serono, MorphoSys, Alimera Sciences, Karyopharm Therapeutics, Bristol-Myers Squibb, C4 Therapeutics, BeiGene, AstraZeneca, Incyte, Bluebird Bio, Kymera, Epizyme, Genmab, MustangBio, Ono Pharmaceutical, Century Therapeutics, Lilly, Caribou Biosciences, Janssen, Takeda, Interius Biotherapeutics, Cellectar, Seagen, Roche/Genentech, ADC Therapeutics, Foresight Diagnostics.Honoraria: Regeneron, AstraZeneca, Janssen, Bristol-Myers Squibb/Celgene, Abbvie, Kite (a Gilead company).Other remuneration: Research funding: Seagen, Bristol-Myers Squibb/Celgene, Cellectis, MustangBio, Regeneron, Merck.M. KuConsultant or advisory role: Roche, AbbVie.Other remuneration: Research funding: Roche, BeiGene.M. HertzbergConsultant or advisory role: Roche, Gildead.Honoraria: Pfizer, Takeda, Janssen.C. P. FoxConsultant or advisory role: AbbVie, Arvinas, BMS, GenMab, Gilead/Kite, Incyte, Morphosys, Ono, Roche, SERB, SOBI.Honoraria: AbbVie, Gilead/Kite, Incyte, Roche, SERB.Other remuneration: Speaker's bureau: AbbVie, Roche, Kite/Gilead. Research funding: AbbVie, BeiGene, Genmab, Incyte, Roche.C. HerbauxConsultant or advisory role: Roche, Janssen, Abbvie, Gilead/Kite, Incyte, Novartis.Honoraria: Roche, Janssen, Abbvie, Gilead/Kite, Incyte, Novartis.Educational grants: Roche, Janssen, Abbvie, Gilead/Kite, Incyte, Novartis.Other remuneration: Research funding: AbbVie, Takeda.D. H. YoonConsultant or advisory role: Roche, Janssen, Amgen, Celgene, Novartis, ABclonal, GI cell, Pharos iBio.Honoraria: Roche, Janssen, Celgene, Kirin Pharmaceuticals, Takeda.Other remuneration: Research funding (self): Samyung, Roche/Genentech, Janssen Oncology, Boryung. Research funding (institution): Celltrion.W. S. KimOther remuneration: Research funding: Sanofi, Beigene, Boryong, Roche, Kyowa-Kirin, Donga.H. AbdulhaqConsultant or advisory role: Novartis, BMS, Genentech, Inc., AbbVie, ADC therapeutics, Pfizer.Honoraria: Novartis, BMS, Genentech, Inc., AbbVie, ADC therapeutics, Pfizer.Educational grants: AbbVie, Genentech, Inc., Actrotech, AstraZeneca.Other remuneration: Speaker's bureau: Genentech, Inc., Alexion. Research funding: Novartis, BMS, Acrotech, ADC therapeutics, Genentech, Inc., Pfizer.W. TownsendConsultant or advisory role: Roche, Abbvie, Kite, Sobi.Honoraria: Roche, Abbvie, Kite, Sobi.Educational grants: Roche, AbbVie.Other remuneration: Research funding (institution): University College London (UCL). My institution (UCL) has received research funding from Roche for conduct of a clinical trial.E. MulvihillEmployment or leadership position: F. Hoffmann-La Roche Ltd.Stock ownership: F. Hoffmann-La Roche Ltd.Educational grants: F. Hoffmann-La Roche Ltd.V. Orellana-NoiaEmployment or leadership position: Genentech, Inc.Stock ownership: Genentech, Inc. (Roche).R. TaEmployment or leadership position: Genentech, Inc.Stock ownership: F. Hoffmann-La Roche.Educational grants: Genentech, Inc.Other remuneration: Research funding: Genentech, Inc. (salaried employee).H. HuangEmployment or leadership position: F. Hoffmann-La Roche Ltd.Other remuneration: Patents, royalties, other intellectual property: F. Hoffmann-La Roche Ltd.M. J. KallemeijnEmployment or leadership position: F. Hoffmann-La Roche Ltd.A. BelousovEmployment or leadership position: F. Hoffmann-La Roche Ltd.Stock ownership: F. Hoffmann-La Roche Ltd.Educational grants: F. Hoffmann-La Roche Ltd.A. BottosEmployment or leadership position: F. Hoffmann-La Roche Ltd.Stock ownership: F. Hoffmann-La Roche Ltd.L. LundbergEmployment or leadership position: F. Hoffmann-La Roche Ltd.Stock ownership: F. Hoffmann-La Roche Ltd.Other remuneration: Patents, royalties, other intellectual property: F. Hoffmann-La Roche Ltd.G. P. GregoryConsultant or advisory role: Roche/Genentech, BMS, Gilead/Kite, Prelude Therapeutics, Clinigen, Merck.Educational grants: Novartis.Other remuneration: Speaker's bureau: Roche/Genentech. Research funding: BeiGene, Merck.\",\"PeriodicalId\":12882,\"journal\":{\"name\":\"Hematological Oncology\",\"volume\":\"43 S3\",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-06-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_76\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematological Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/hon.70093_76\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70093_76","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}

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摘要

Glofitamab是一种CD20:CD3双特异性抗体，在R/R DLBCL治疗≥2个既往治疗线(LOT；Dickinson等人。NEJM 2022)。在3期STARGLO试验中，glofitgemox在自体干细胞移植(ASCT)-不符合条件的R/R DLBCL （Abramson等）中显示了比利妥昔单抗(R)-GemOx的总生存期（OS）和无进展生存期（PFS）的益处。《柳叶刀》2024年)。在这里，我们展示了STARGLO试验（NCT04408638）的最新疗效和安全性，包括对完全缓解（CR）患者（pts）的里程碑式分析。方法：患者以2:1随机分组，接受glofitt - gemox（8个周期加4个周期glofitumab单药治疗）或R-GemOx（8个周期），并根据先前LOT的数量（1 vs.≥2）和最后一次治疗的难治性进行分层。在obinutuzumab预处理后，glofitamab在Cycle (C) 1中作为每周加强剂量（2.5/ 10mg）给予，然后从C2 Day 1开始每21天给予30mg靶剂量。先前只有1次LOT的患者必须是不符合asct条件的。主要终点为OS。次要终点包括独立审查委员会（IRC）评估的PFS和CR率。对治疗结束时CR （EOT）的pts进行了里程碑式分析。结果：274例患者(Glofit-GemOx, n = 183；R-GemOx, n = 91)， 172例（62.8%）既往有1次LOT， 102例（37.2%）既往有≥2次LOT， 153例（55.8%）为原发性难治性，166例（60.6%）对其最后一次治疗难治性。与初步分析相比，基线特征没有变化，各组之间平衡良好。随访2年(截止日期：2024年6月17日；中位随访时间：24.7个月[mo])， Glofit-GemOx继续提供优越的OS(中位：不可评估[NE] vs. 13.5个月；风险比[HR] 0.60, 95%可信区间[CI]: 0.42-0.85)， irc评估的中位PFS (13.8 vs. 3.6个月；相对于R-GemOx， HR 0.41, 95% CI: 0.29-0.58)和CR率（58.5比25.3%）。对于glofit - gemox治疗的CR患者（n = 107）， CR的中位持续时间未达到(95% CI: 27.2 ne；中位CR随访时间为18.2个月[范围：15.2-19.3])。在EOT时有CR的患者中（n = 82）， EOT后1年的OS和PFS率分别为89.3%和82.4%。Glofit-GemOx的安全性没有变化。细胞因子释放综合征（CRS）是格非他单抗暴露患者中最常见的不良事件(Grade [Gr] 1, 32.0%；Gr 2, 10.5%；3年级，2.3%)。4例患者发生与免疫效应细胞相关神经毒性综合征相符的事件(均伴有CRS；大多数Gr 1-2 [n = 3])。探索性生物标志物和免疫恢复数据将被提出。结论：经过2年的随访，与R- gemox相比，Glofit-GemOx对asct不合格的R/R DLBCL患者的OS和PFS具有临床意义的益处，大多数（82%）EOT时CR患者仍处于缓解期。安全性概况与每种药物的已知风险一致。最新的分析表明，在接受固定时间Glofit-GemOx治疗的R/R DLBCL患者中，持续的缓解和持续的OS获益。研究经费声明：STARGLO （GO41944）由F. Hoffmann-La Roche Ltd.赞助。第三方编辑协助，在所有作者的指导下，由Inizio公司Ashfield MedComms的Roisin Weaver硕士提供，并由F. Hoffmann-La Roche ltd .资助。encore摘要：©2025 American Society of Clinical Oncology， Inc.。在获得许可的情况下重用。该摘要已被接受并在ASCO 2025年年会上提交。版权所有。关键词：侵袭性b细胞非霍奇金淋巴瘤；潜在的利益冲突来源：J。顾问或顾问角色：Celgene， Novartis, Abbvie, Kite（吉利德公司），EMD Serono, MorphoSys, Alimera Sciences, Karyopharm Therapeutics, Bristol-Myers Squibb, C4 Therapeutics, BeiGene, AstraZeneca, Incyte, Bluebird Bio, Kymera, Epizyme, Genmab, MustangBio, Ono Pharmaceutical, Century Therapeutics, Lilly, Caribou Biosciences, Janssen, Takeda, Interius biotheraptics, Cellectar, Seagen, Roche/Genentech, ADC Therapeutics, Foresight Diagnostics。包括：Regeneron， AstraZeneca, Janssen, Bristol-Myers Squibb/Celgene, Abbvie, Kite（吉利德公司）。其他报酬：研究经费：Seagen， Bristol-Myers Squibb/Celgene, Cellectis, MustangBio, Regeneron, Merck.M。顾问或顾问角色：罗氏，艾伯维。其他报酬：研究经费：Roche， beigene m。顾问或顾问角色：罗氏，吉尔迪姆。辉瑞，武田，杨森。c。顾问或顾问角色：AbbVie、Arvinas、BMS、GenMab、Gilead/Kite、Incyte、Morphosys、Ono、Roche、SERB、SOBI。荣誉：艾伯维，吉利德/凯特，Incyte，罗氏，塞尔维亚。其他报酬：演讲者办公室：艾伯维、罗氏、凯特/吉利德。研究经费：艾伯维、百济神州、Genmab、Incyte、罗氏公司。顾问或顾问角色：罗氏、杨森、艾伯维、吉利德/Kite、Incyte、诺华。荣誉：罗氏，杨森，艾伯维，吉利德/Kite， Incyte，诺华。教育资助：罗氏、杨森、艾伯维、吉利德/Kite、Incyte、诺华。其他报酬：研究经费：AbbVie， Takeda.D。顾问或顾问角色：罗氏，杨森，安进，Celgene，诺华，ABclonal, GI cell, Pharos iBio。罗氏，杨森，新基，麒麟制药，武田。其他报酬：研究经费（自我）：三明、罗氏/基因泰克、杨森肿瘤、宝宁。研究经费（单位）：Celltrion.W。研究经费：赛诺菲、百济神州、博宁、罗氏、京和麒麟、Donga.H。abdulhaq顾问或顾问角色：诺华，BMS, Genentech, Inc., AbbVie, ADC therapeutics，辉瑞。荣誉：诺华，BMS，基因泰克，艾伯维，ADC治疗，辉瑞。教育资助：AbbVie， Genentech, Inc, Actrotech, AstraZeneca。其他报酬：演讲者办公室：基因泰克公司，亚历克西翁。研究经费：诺华，BMS, Acrotech, ADC therapeutics, Genentech, Inc.，辉瑞。顾问或顾问角色：罗氏，艾伯维，Kite, Sobi。罗氏、艾伯维、凯特、索比。教育资助：罗氏，艾伯维。研究经费（机构）：伦敦大学学院（UCL）。我所在的机构（UCL）已经获得了罗氏公司的研究经费，用于进行一项临床试验。任职或领导职务：F. Hoffmann-La Roche ltd .持股：F. Hoffmann-La Roche ltd .教育资助：F. Hoffmann-La Roche Ltd.V。任职或领导职务：Genentech， Inc.股份：Genentech， Inc. (Roche). r。任职或领导职务：Genentech， inc .股份：F. Hoffmann-La Roche。其他报酬：研究经费：Genentech， Inc.（受薪员工）。任职或领导职务：F. Hoffmann-La Roche ltd .其他报酬：专利、特许权使用费、其他知识产权：F. Hoffmann-La Roche ltd .任职或领导职务：F. Hoffmann-La Roche ltd .。任职或领导职务：F. Hoffmann-La Roche ltd .持有股份：F. Hoffmann-La Roche ltd .教育资助：F. Hoffmann-La Roche Ltd.A。任职或领导职务：F. Hoffmann-La Roche ltd .股权：F. Hoffmann-La Roche Ltd.L任职或领导职务：F. Hoffmann-La Roche ltd .股权：F. Hoffmann-La Roche ltd .其他报酬：专利，版税，其他知识产权：F. Hoffmann-La Roche ltd .顾问或顾问角色：罗氏/基因泰克、BMS、吉利德/Kite、Prelude Therapeutics、Clinigen、默克。教育资助：诺华。其他报酬：演讲局：罗氏/基因泰克。研究经费：百济神州，默克。

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GLOFITAMAB PLUS GEMCITABINE AND OXALIPLATIN (Glofit-GemOx) IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): 2-YEAR FOLLOW-UP OF STARGLO

Introduction: Glofitamab, a CD20:CD3 bispecific antibody, has shown durable responses as fixed duration monotherapy in R/R DLBCL after ≥ 2 prior lines of therapy (LOT; Dickinson et al. NEJM 2022). In the Phase 3 STARGLO trial, Glofit-GemOx demonstrated overall survival (OS) and progression-free survival (PFS) benefits over rituximab (R)-GemOx in autologous stem cell transplant (ASCT)-ineligible R/R DLBCL (Abramson et al. Lancet 2024). Here, we present updated efficacy and safety from the STARGLO trial (NCT04408638), including landmark analyses of patients (pts) in complete remission (CR).

Methods: Pts were randomized 2:1 to receive Glofit-GemOx (8 cycles plus 4 cycles glofitamab monotherapy) or R-GemOx (8 cycles) and stratified by number of prior LOT (1 vs. ≥ 2) and refractoriness to their last therapy. After obinutuzumab pretreatment, glofitamab was given in Cycle (C) 1 as weekly step-up doses (2.5/10 mg) then 30 mg target dose every 21 days from C2 Day 1. Pts with only 1 prior LOT must have been ASCT-ineligible. Primary endpoint was OS. Secondary endpoints included independent review committee (IRC)-assessed PFS and CR rate. A landmark analysis of pts in CR at end of treatment (EOT) was performed.

Results: Of 274 pts (Glofit-GemOx, n = 183; R-GemOx, n = 91), 172 (62.8%) had 1 prior LOT, 102 (37.2%) had ≥ 2 prior LOT, 153 (55.8%) were primary refractory, and 166 (60.6%) were refractory to their last therapy. Baseline characteristics were unchanged compared with the primary analysis and well balanced across arms.

With 2 years (yrs) of follow-up (data cut off: June 17, 2024; median follow-up: 24.7 months [mo]), Glofit-GemOx continued to confer superior OS (median: not evaluable [NE] vs. 13.5 mo; hazard ratio [HR] 0.60, 95% confidence interval [CI]: 0.42–0.85), median IRC-assessed PFS (13.8 vs. 3.6 mo; HR 0.41, 95% CI: 0.29–0.58), and CR rate (58.5 vs. 25.3%) versus R-GemOx. For Glofit-GemOx-treated pts in CR (n = 107), median duration of CR was not reached (95% CI: 27.2–NE; median CR follow-up, 18.2 mo [range: 15.2–19.3]). In pts with a CR at EOT (n = 82), the OS and PFS rates 1 yr after EOT were 89.3% and 82.4%, respectively.

The Glofit-GemOx safety profile was unchanged. Cytokine release syndrome (CRS) was the most common adverse event in glofitamab-exposed pts (Grade [Gr] 1, 32.0%; Gr 2, 10.5%; Gr 3, 2.3%). Events consistent with immune effector cell-associated neurotoxicity syndrome occurred in 4 pts (all concurrent with CRS; most Gr 1–2 [n = 3]). Exploratory biomarker and immune recovery data will be presented.

Conclusions: With 2 yrs of follow-up, Glofit-GemOx sustained a clinically meaningful benefit in OS and PFS versus R-GemOx in ASCT-ineligible pts with R/R DLBCL, with most (82%) pts in CR at EOT still in remission. The safety profile was consistent with known risks of each drug. The updated analyses demonstrate durable remissions and maintained OS benefit in pts with R/R DLBCL treated with fixed duration Glofit-GemOx.

Research funding declaration: STARGLO (GO41944) is sponsored by F. Hoffmann-La Roche Ltd. Third-party editorial assistance, under the direction of all authors, was provided by Roisin Weaver, MSc, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.

Encore Abstract: © 2025 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the ASCO 2025 Annual Meeting. All rights reserved.

Keywords: aggressive B-cell non-Hodgkin lymphoma; immunotherapy

Potential sources of conflict of interest:

J. S. Abramson

Consultant or advisory role: Celgene, Novartis, Abbvie, Kite (a Gilead company), EMD Serono, MorphoSys, Alimera Sciences, Karyopharm Therapeutics, Bristol-Myers Squibb, C4 Therapeutics, BeiGene, AstraZeneca, Incyte, Bluebird Bio, Kymera, Epizyme, Genmab, MustangBio, Ono Pharmaceutical, Century Therapeutics, Lilly, Caribou Biosciences, Janssen, Takeda, Interius Biotherapeutics, Cellectar, Seagen, Roche/Genentech, ADC Therapeutics, Foresight Diagnostics.

Honoraria: Regeneron, AstraZeneca, Janssen, Bristol-Myers Squibb/Celgene, Abbvie, Kite (a Gilead company).

Other remuneration: Research funding: Seagen, Bristol-Myers Squibb/Celgene, Cellectis, MustangBio, Regeneron, Merck.

M. Ku

Consultant or advisory role: Roche, AbbVie.

Other remuneration: Research funding: Roche, BeiGene.

M. Hertzberg

Consultant or advisory role: Roche, Gildead.

Honoraria: Pfizer, Takeda, Janssen.

C. P. Fox

Consultant or advisory role: AbbVie, Arvinas, BMS, GenMab, Gilead/Kite, Incyte, Morphosys, Ono, Roche, SERB, SOBI.

Honoraria: AbbVie, Gilead/Kite, Incyte, Roche, SERB.

Other remuneration: Speaker's bureau: AbbVie, Roche, Kite/Gilead. Research funding: AbbVie, BeiGene, Genmab, Incyte, Roche.

C. Herbaux

Consultant or advisory role: Roche, Janssen, Abbvie, Gilead/Kite, Incyte, Novartis.

Honoraria: Roche, Janssen, Abbvie, Gilead/Kite, Incyte, Novartis.

Educational grants: Roche, Janssen, Abbvie, Gilead/Kite, Incyte, Novartis.

Other remuneration: Research funding: AbbVie, Takeda.

D. H. Yoon

Consultant or advisory role: Roche, Janssen, Amgen, Celgene, Novartis, ABclonal, GI cell, Pharos iBio.

Honoraria: Roche, Janssen, Celgene, Kirin Pharmaceuticals, Takeda.

Other remuneration: Research funding (self): Samyung, Roche/Genentech, Janssen Oncology, Boryung. Research funding (institution): Celltrion.

W. S. Kim

Other remuneration: Research funding: Sanofi, Beigene, Boryong, Roche, Kyowa-Kirin, Donga.

H. Abdulhaq

Consultant or advisory role: Novartis, BMS, Genentech, Inc., AbbVie, ADC therapeutics, Pfizer.

Honoraria: Novartis, BMS, Genentech, Inc., AbbVie, ADC therapeutics, Pfizer.

Educational grants: AbbVie, Genentech, Inc., Actrotech, AstraZeneca.

Other remuneration: Speaker's bureau: Genentech, Inc., Alexion. Research funding: Novartis, BMS, Acrotech, ADC therapeutics, Genentech, Inc., Pfizer.

W. Townsend

Consultant or advisory role: Roche, Abbvie, Kite, Sobi.

Honoraria: Roche, Abbvie, Kite, Sobi.

Educational grants: Roche, AbbVie.

Other remuneration: Research funding (institution): University College London (UCL). My institution (UCL) has received research funding from Roche for conduct of a clinical trial.

E. Mulvihill

Employment or leadership position: F. Hoffmann-La Roche Ltd.

Stock ownership: F. Hoffmann-La Roche Ltd.

Educational grants: F. Hoffmann-La Roche Ltd.

V. Orellana-Noia

Employment or leadership position: Genentech, Inc.

Stock ownership: Genentech, Inc. (Roche).

R. Ta

Employment or leadership position: Genentech, Inc.

Stock ownership: F. Hoffmann-La Roche.

Educational grants: Genentech, Inc.

Other remuneration: Research funding: Genentech, Inc. (salaried employee).

H. Huang

Employment or leadership position: F. Hoffmann-La Roche Ltd.

Other remuneration: Patents, royalties, other intellectual property: F. Hoffmann-La Roche Ltd.

M. J. Kallemeijn

Employment or leadership position: F. Hoffmann-La Roche Ltd.

A. Belousov

Employment or leadership position: F. Hoffmann-La Roche Ltd.

Stock ownership: F. Hoffmann-La Roche Ltd.

Educational grants: F. Hoffmann-La Roche Ltd.

A. Bottos

Employment or leadership position: F. Hoffmann-La Roche Ltd.

Stock ownership: F. Hoffmann-La Roche Ltd.

L. Lundberg

Employment or leadership position: F. Hoffmann-La Roche Ltd.

Stock ownership: F. Hoffmann-La Roche Ltd.

Other remuneration: Patents, royalties, other intellectual property: F. Hoffmann-La Roche Ltd.

G. P. Gregory

Consultant or advisory role: Roche/Genentech, BMS, Gilead/Kite, Prelude Therapeutics, Clinigen, Merck.

Educational grants: Novartis.

Other remuneration: Speaker's bureau: Roche/Genentech. Research funding: BeiGene, Merck.

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来源期刊

Hematological Oncology 医学-血液学

CiteScore

4.20

自引率

6.10%

发文量

147

审稿时长

>12 weeks

期刊介绍： Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged: -Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders -Diagnostic investigations, including imaging and laboratory assays -Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases -Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies -Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems. Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.