To the Editor:Bispecific antibodies [bsAb] targeting B-cell maturation antigen [BCMA] and G-protein-coupled receptor class C group 5 member D [GPRC5D] have demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma [MM], with single-agent response rates from 57–71% [1,2,3,4,5,6].

致编辑：靶向B细胞成熟抗原（BCMA）和G蛋白偶联受体C组5成员D（GPRC5D）的双特异性抗体（bsAb）在复发/难治性多发性骨髓瘤（MM）患者中表现出深度和持久的反应，单药反应率为57-71%[1,2,3,4,5,6]。

Currently, two BCMA- and one GPRC5D-targeting bsAb—teclistamab, elranatamab, and talquetamab, respectively—have received FDA accelerated approval in patients with relapsed/refractory MM after four or more prior lines of therapy. Notably, in their pivotal trials, the bsAb was administered continuously until disease progression or intolerance.

目前，针对bsAb-teclistamab，elranatamab和talquetamab的两种BCMA和一种GPRC5D分别在四种或更多种先前治疗方案后复发/难治性MM患者中获得FDA加速批准。值得注意的是，在他们的关键试验中，bsAb持续给药直至疾病进展或不耐受。

However, fixed-duration dosing with treatment-free interval(s) is being explored [7, 8] and maybe a preferred approach from both efficacy and safety standpoints for several reasons. First, continuous exposure to T-cell engaging bsAb can lead to T-cell exhaustion, as highlighted in preclinical studies, and treatment-free intervals are associated with transcriptional reprogramming and functional reinvigoration of T-cells [9].

然而，正在探索无治疗间隔的固定持续时间给药[7，8]，并且出于几个原因，可能是从疗效和安全性角度来看的首选方法。首先，如临床前研究所强调的，持续暴露于T细胞参与bsAb可导致T细胞耗竭，无治疗间隔与T细胞的转录重编程和功能恢复有关。

T-cell exhaustion from continuous dosing may lead to lower efficacy of subsequent T-cell redirecting therapies, as potentially suggested by lower response rates to cilta-cel among patients with prior bsAb exposure [10]. Second, continuous exposure may drive some mechanisms of relapse. Correlative studies on plasma cells at relapse have shown a higher incidence of mutational events or biallelic loss affecting the BCMA-encoding gene TNFRSF17 following bsAb than after CAR T-cells (43% vs 6%, respectively) [11].

连续给药的T细胞耗竭可能导致随后的T细胞重定向疗法的疗效降低，这可能是由于先前bsAb暴露的患者对cilta-cel的反应率较低所致。其次，持续暴露可能会导致某些复发机制。复发时浆细胞的相关研究表明，bsAb后影响BCMA编码基因TNFRSF17的突变事件或双等位基因丢失的发生率高于CAR T细胞（分别为43%和6%）[11]。

Third, infection-related morbidity and mortality have emerged as one of the key toxicities with BCMA bsAb in MM [12,13,14], with the depth and duration of immunosuppression likely to correlate stron.

第三，感染相关的发病率和死亡率已成为MM中BCMA-bsAb的关键毒性之一[12，13，14]，免疫抑制的深度和持续时间可能与stron相关。

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Download referencesAcknowledgementsMedical College of Wisconsin, Advancing a Healthier Wisconsin Endowment-CTSI KL2 award and pilot grant (MM).Author informationAuthors and AffiliationsColumbia University Irving Medical Center, New York, NY, USARajshekhar Chakraborty & Suzanne LentzschMedical College of Wisconsin, Milwaukee, WI, USAHeloise Cheruvalath, Anannya Patwari, Aniko Szabo, Binod Dhakal, Anita D’Souza & Meera MohanUniversity of Arkansas for Medical Sciences, Little Rock, AR, USACarolina SchinkeHuntsman Cancer Center, University of Utah, Salt Lake City, UT, USAGhulam Rehman Mohyuddin & Kelley JulianDana Farber Cancer Institute and Harvard Medical School, Boston, MA, USAShonali Midha & Patrick CostelloThe Institute of Cancer Research, London, UKMartin KaiserSir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, AustraliaMelissa Ng Liet Hing, Simon J.

下载参考文献致谢威斯康星州医学院，推进更健康的威斯康星州捐赠CTSI KL2奖和试点拨款（MM）。作者信息作者和附属机构哥伦比亚大学欧文医学中心，纽约州，威斯康星州密尔沃基，威斯康星州，威斯康星州，威斯康星州，威斯康星州，威斯康星州，威斯康星州，威斯康星州，乌萨海伦·切鲁瓦拉，阿纳尼亚·帕特瓦里，阿肯色州阿尼科·萨博，比诺德·达卡尔，安妮塔·德索扎和米拉·莫汉纳大学医学院，阿肯色州小石城，美国卡罗莱纳州辛克亨茨曼癌症中心，犹他大学，盐湖城，犹他州，乌萨古拉姆·雷赫曼·莫尤丁和凯利·朱利安·达纳·法伯癌症研究所和哈佛医学院，波士顿，马萨诸塞州，美国Shonali Midha＆Patrick Costelloth伦敦癌症研究所，UKMartin KaiserSir Peter MacCallum澳大利亚帕克维尔墨尔本大学肿瘤学系Alissa Ng Liet Hing，Simon J。

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PubMed Google ScholarContributionsAD, MM, and RC conceived the study design. RC, HC, AP, CS, GRM, KJ, SM, PC, MNLH, and MM extracted clinical data from medical records. AS performed statistical analysis. RC, ERSC, and MM wrote the first draft of the manuscript. All authors provided critical feedback on the first draft and approved the final draft of the manuscript.Corresponding authorCorrespondence to.

PubMed Google ScholarContributionsAD，MM和RC构思了研究设计。RC，HC，AP，CS，GRM，KJ，SM，PC，MNLH和MM从病历中提取临床数据。进行统计分析。RC，ERSC和MM撰写了手稿的初稿。所有作者都对初稿提供了批判性反馈，并批准了稿件的最终草稿。对应作者对应。

Rajshekhar Chakraborty.Ethics declarations

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Competing interests

相互竞争的利益

RC: Consulting/Advisory Board-Janssen, Sanofi, Adaptive Biotech. SL: Consultant and/or Advisor for Adaptive Biotechnologies, Alexion Therapeutics, Bristol-Meyers-Squibb, Caelum Biosciences, Janssen Pharmaceuticals, Karyopharm Therapeutics, Oncopeptides AB, GSK, Abbvie, Janssen, Pfizer, and Takeda Pharmaceutical Company; receives research funding from Celgene, Inc., Sanofi, Zentalis; received honoraria from Clinical Care Options and Regeneron Pharmaceuticals; and has Royalties/Patents with Caelum Biosciences.

RC：咨询/顾问委员会Janssen，赛诺菲，Adaptive Biotech。SL：适应性生物技术，Alexion Therapeutics，Bristol Meyers Squibb，Caelum Biosciences，Janssen Pharmaceuticals，Karyopharm Therapeutics，Oncopeptides AB，GSK，Abbvie，Janssen，Pfizer和武田制药公司的顾问和/或顾问；获得Celgene，Inc.，赛诺菲，Zentalis的研究资金；获得了Clinical Care Options和Regeneron Pharmaceuticals的酬金；并拥有Caelum Biosciences的版税/专利。

In addition, SL has a patent CAEL-101 with royalties paid to Columbia University. AD: Institutional research funding from AbbVie, Caelum, Janssen, Novartis, Prothena, Sanofi, Takeda, and TeneoBio; advisory board fees from BMS, Pfizer, and Janssen; and consulting fees from Prothena and Janssen. BD: Consultant-BMS, Genentech, Janssen, Karyopharm, Natera, Pfozer.

此外，SL拥有CAEL-101专利，并向哥伦比亚大学支付了版税。广告：来自AbbVie，Caelum，Janssen，Novartis，Prothena，Sanofi，Takeda和TeneoBio的机构研究资金；BMS，辉瑞和杨森的咨询委员会费用；以及Prothena和Janssen的咨询费。BD：顾问BMS，Genentech，Janssen，Karyopharm，Natera，Pfozer。

SH: Consultant-Celgene, Genentech, Janssen, Novartis. MK: Honoraria: Janssen, Takeda, AbbVie, and Sanofi; consulting or advisory role: AbbVie, GSK, Janssen, Pfizer, Seattle Genetics, Takeda, Adaptive and Poolbeg Pharma. Research funding: BMS/Celgene (to institution) and Janssen (to institution). MM: Institutional Research Funding: Sanofi S.A, GlaxoSmithKline plc, Takeda Pharmaceutical Company, Ionis Pharmaceuticals, Bristol-Myers Squibb Company, Celgene Corporation, Sanofi S.A, and Amgen Inc; Consultancy: Sanofi S.A, Bristol-Myers Squibb Company, and Pfizer; Honorarium: Blood Cancer Today, MJH life sciences.

SH：顾问Celgene，Genentech，Janssen，Novartis。MK：酬金：杨森，武田，艾伯维和赛诺菲；咨询或顾问角色：AbbVie，GSK，Janssen，辉瑞，西雅图遗传学，武田，Adaptive和Poolbeg Pharma。研究资金：BMS/Celgene（机构）和Janssen（机构）。MM：机构研究资金：赛诺菲公司，葛兰素史克公司，武田制药公司，Ionis制药公司，百时美施贵宝公司，Celgene公司，赛诺菲公司和安进公司；咨询公司：赛诺菲公司，百时美施贵宝公司和辉瑞公司；荣誉：今日血癌，MJH生命科学。

The remaining authors declare no relevant financial conflicts of interest..

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Reprints and permissionsAbout this articleCite this articleChakraborty, R., Cheruvalath, H., Patwari, A. et al. Sustained remission following finite duration bispecific antibody therapy in patients with relapsed/refractory myeloma.

转载和许可本文引用本文Chakraborty，R.，Cheruvalath，H.，Patwari，A。等人。复发/难治性骨髓瘤患者在有限时间双特异性抗体治疗后持续缓解。

Blood Cancer J. 14, 137 (2024). https://doi.org/10.1038/s41408-024-01114-7Download citationReceived: 23 April 2024Revised: 27 June 2024Accepted: 26 July 2024Published: 12 August 2024DOI: https://doi.org/10.1038/s41408-024-01114-7Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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