Characterization and Management of Cytokine Release Syndrome From the MonumenTAL-1 Study of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-10-02 DOI:10.1002/cam4.71276

Niels W. C. J. van de Donk, Ajai Chari, Thomas Martin, Amrita Krishnan, Leo Rasche, Jing Christine Ye, Rakesh Popat, Brea Lipe, Cesar Rodriguez, Carolina Schinke, Sheri Skerget, Deeksha Vishwamitra, Raluca Verona, Jue Gong, Indrajeet Singh, Michela Campagna, Tara Masterson, Brandi Hilder, Jaszianne Tolbert, Thomas Renaud, M. Damiette Smit, Christoph Heuck, Maria-Victoria Mateos

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引用次数: 0

Abstract

Introduction

Cytokine release syndrome (CRS) is a common adverse event associated with T-cell redirection therapies (TCRT), including talquetamab, the first GPRC5D × CD3 bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM). We describe CRS with talquetamab and implications for clinical practice.

Methods

Patients without prior TCRT received talquetamab 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W), with two or three step-up doses, respectively, plus pretreatment with a glucocorticoid, antihistamine, and antipyretic. A separate cohort of patients with prior TCRT received talquetamab at either the QW or Q2W schedule. CRS was graded per American Society for Transplantation and Cellular Therapy criteria and managed per study protocol.

Results

Across talquetamab QW (n = 143), Q2W (n = 145), and prior TCRT (n = 51) cohorts, most CRS events occurred during step-up doses and were grade 1 or 2; grade 3 CRS events were rare. Approximately one-third of patients experienced more than one CRS event. Fewer patients experienced subsequent CRS events if tocilizumab was used versus not used to treat their first CRS event. Overall response rates with talquetamab were similar among patients with and without tocilizumab to manage CRS. Baseline characteristics were not associated with CRS incidence, recurrence, duration, or severity, whereas immune biomarkers showed some trends in association with CRS parameters.

Conclusion

CRS outcomes with talquetamab were consistent with those seen with other TCRT in RRMM, including teclistamab (BCMA×CD3 bispecific antibody), indicating a similar clinical approach, including early vigilance and prompt treatment of CRS.

Trial Registration

NCT03399799/NCT04634552

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塔尔克他单抗治疗复发/难治性多发性骨髓瘤患者的细胞因子释放综合征的特征和管理

细胞因子释放综合征（CRS）是与t细胞重定向治疗（TCRT）相关的常见不良事件，包括talquetamab，第一个批准用于复发/难治性多发性骨髓瘤（RRMM）的GPRC5D × CD3双特异性抗体。我们描述CRS与talquetamab和临床实践的意义。方法：未接受TCRT治疗的患者给予talquetamab每周0.4 mg/kg （QW）和每隔一周0.8 mg/kg (Q2W)，分别给予2次或3次强化剂量，外加糖皮质激素、抗组胺药和退烧药的预处理。另一组先前接受TCRT的患者在QW或Q2W计划中接受了talquetamab。CRS按照美国移植和细胞治疗协会的标准进行分级，并按照研究方案进行管理。结果：在talquetamab QW （n = 143）、Q2W （n = 145）和之前的TCRT （n = 51）队列中，大多数CRS事件发生在增加剂量期间，为1级或2级；3级CRS事件罕见。大约三分之一的患者经历了一次以上的CRS事件。使用托珠单抗治疗第一次CRS事件的患者比不使用托珠单抗治疗的患者发生后续CRS事件的患者少。在使用托珠单抗和不使用托珠单抗治疗CRS的患者中，talquetamab的总缓解率相似。基线特征与CRS发生率、复发、持续时间或严重程度无关，而免疫生物标志物显示出与CRS参数相关的一些趋势。结论：在RRMM中，talquetamab与teclistamab （BCMA×CD3双特异性抗体）等其他TCRT的CRS结果一致，表明临床方法相似，包括早期警惕和及时治疗CRS。试验注册：NCT03399799/NCT04634552。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.