Mayo Clinic, 5881 E. Mayo Boulevard, Phoenix, AZ, 85054, USA.
Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Target Oncol. 2021 May;16(3):295-308. doi: 10.1007/s11523-021-00802-9. Epub 2021 Mar 9.
Dysregulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin signaling is common in both indolent and aggressive forms of malignant lymphoma, for which several targeted therapies have been developed. Copanlisib is a highly selective and potent intravenous pan-class I PI3K inhibitor that has demonstrated durable objective responses and a manageable safety profile in heavily pre-treated patients with indolent lymphomas. As a result, copanlisib monotherapy received accelerated approval from the US Food and Drug Administration for the treatment of adults with relapsed follicular lymphoma who have received at least two systemic therapies, and breakthrough designation for patients with pre-treated relapsed or refractory marginal zone lymphoma. Hyperglycemia and hypertension are among the most frequently reported adverse events with copanlisib monotherapy, and are infusion-related, transient, and manageable with standard therapies. Mild diarrhea is also a common adverse event with copanlisib monotherapy; there is no evidence of worsening severity of diarrhea, or serious gastrointestinal toxicities such as colitis or severe liver enzyme elevations, which have been reported with orally administered PI3K inhibitors. The intravenous route of administration and intermittent dosing schedule of copanlisib may support a favorable tolerability profile over continually administered oral alternatives. Ongoing studies of copanlisib in combination with rituximab and standard-of-care chemotherapy in patients with relapsed indolent lymphoma have the potential to support the use of copanlisib in the second-line setting, providing a much-needed additional therapeutic option in this underserved patient population.
磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B/雷帕霉素哺乳动物靶蛋白信号转导失调在惰性和侵袭性恶性淋巴瘤中都很常见，为此已经开发了几种靶向治疗方法。Copanlisib 是一种高度选择性和强效的静脉内泛 I 类 PI3K 抑制剂，在经过大量预处理的惰性淋巴瘤患者中，已证明其具有持久的客观缓解和可管理的安全性。因此，Copanlisib 单药治疗获得了美国食品和药物管理局的加速批准，用于治疗至少接受过两种全身治疗的复发性滤泡性淋巴瘤成人患者，以及用于治疗经过预处理的复发性或难治性边缘区淋巴瘤患者的突破性治疗药物认定。高血糖和高血压是 Copanlisib 单药治疗最常报告的不良事件，与输液相关，是短暂的，可以用标准疗法进行管理。轻度腹泻也是 Copanlisib 单药治疗的常见不良事件；没有证据表明腹泻严重程度恶化，也没有报道过口服 PI3K 抑制剂所报告的结肠炎或严重肝酶升高等严重胃肠道毒性。Copanlisib 的静脉给药途径和间歇性给药方案可能比连续口服替代方案具有更好的耐受性。Copanlisib 联合利妥昔单抗和标准护理化疗治疗复发性惰性淋巴瘤的研究有可能支持在二线治疗中使用 Copanlisib，为这一未满足需求的患者群体提供急需的额外治疗选择。
