Pirtobrutinib: A New and Distinctive Treatment Option for B-Cell Malignancies.

IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Annals of Pharmacotherapy Pub Date : 2024-10-01 Epub Date: 2024-01-18 DOI:10.1177/10600280231223737
Madeline D Schultze, David J Reeves
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引用次数: 0

Abstract

Objective: The objective was to evaluate the efficacy/safety of pirtobrutinib in the treatment of B-cell malignancies and distinguish it from other available Bruton's tyrosine kinase (BTK) inhibitors.

Data sources: A literature search of PubMed (January 2021 through November 2023) and Clinicaltrials.gov was conducted using terms pirtobrutinib, Jaypirca, and LOXO 305. Licensing trials of available BTK inhibitors were also reviewed.

Study selection and data extraction: Relevant English-language clinical trials were evaluated.

Data synthesis: Pirtobrutinib was approved by the US Food and Drug Administration for the treatment of relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) based largely on a phase 1/2 study in B-cell malignancies. Pirtobrutinib demonstrated a 73% overall response rate (ORR) in the CLL population and 58% in MCL. Pirtobrutinib has activity in patients resistant to earlier-generation, covalent BTK inhibitors. In fact, the ORRs were similar in BTK-pretreated and naïve patients. Adverse effects include fatigue, diarrhea, bleeding, and infection. Atrial fibrillation, a class effect of BTK inhibitors, may be less common with pirtobrutinib.

Relevance to patient care and clinical practice in comparison with existing drugs: Compared with earlier-generation BTK inhibitors, pirtobrutinib is more selective for BTK and binds noncovalently to the receptor. Ongoing studies are evaluating pirtobrutinib's use in multiple B-cell malignancies and comparing it with other BTK inhibitors.

Conclusion: The characteristics of pirtobrutinib render it useful in the treatment of B-cell malignancies no longer responding to a previous BTK inhibitor, and results from ongoing clinical trials may support future expanded use.

Pirtobrutinib:治疗 B 细胞恶性肿瘤的独特新疗法。
目的目的是评估吡咯替尼治疗B细胞恶性肿瘤的疗效/安全性,并将其与其他可用的布鲁顿酪氨酸激酶(BTK)抑制剂区分开来:使用术语 pirtobrutinib、Jaypirca 和 LOXO 305 对 PubMed(2021 年 1 月至 2023 年 11 月)和 Clinicaltrials.gov 进行了文献检索。此外,还审查了现有 BTK 抑制剂的许可试验:评估了相关的英文临床试验:美国食品和药物管理局主要根据一项针对B细胞恶性肿瘤的1/2期研究,批准皮罗替尼用于治疗复发/难治性套细胞淋巴瘤(MCL)和慢性淋巴细胞白血病(CLL)。Pirtobrutinib在CLL人群中的总反应率(ORR)为73%,在MCL人群中的总反应率(ORR)为58%。Pirtobrutinib 对早一代共价 BTK 抑制剂耐药的患者具有活性。事实上,BTK 预处理患者和新药患者的 ORR 相似。不良反应包括疲劳、腹泻、出血和感染。心房颤动是BTK抑制剂的一类效应,但皮罗布替尼可能较少见:与早期BTK抑制剂相比,皮罗布替尼对BTK的选择性更强,并能与受体非共价结合。目前正在进行的研究正在评估吡咯替尼在多种B细胞恶性肿瘤中的应用,并将其与其他BTK抑制剂进行比较:结论:皮尔曲替尼的特性使其可用于治疗对之前的BTK抑制剂不再有反应的B细胞恶性肿瘤,正在进行的临床试验结果可能支持其在未来的扩大应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.70
自引率
0.00%
发文量
166
审稿时长
3-8 weeks
期刊介绍: Annals of Pharmacotherapy (AOP) is a peer-reviewed journal that advances pharmacotherapy throughout the world by publishing high-quality research and review articles to achieve the most desired health outcomes.The articles provide cutting-edge information about the most efficient, safe and cost-effective pharmacotherapy for the treatment and prevention of various illnesses. This journal is a member of the Committee on Publication Ethics (COPE). Average time from submission to first decision: 14 days
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