Faculté de Médecine Lyon-SudBernard, Hospices Civils De Lyon, Lyon-Sud, Department Of Hematology, Pierre-Bénite France And Université De Lyon, Université Claude , Oullins, France.
Expert Opin Investig Drugs. 2020 Oct;29(10):1079-1088. doi: 10.1080/13543784.2020.1800638. Epub 2020 Aug 12.
New agents for managing B-cell non-Hodgkin lymphomas (NHLs) are needed, particularly for high-risk and relapsed or refractory patients. Antibody-drug conjugates (ADCs) provide targeted drug delivery to tumors with a broaden therapeutic index of cytotoxic agent, reducing their systemic toxicity while increasing intracellular concentrations. Polatuzumab vedotin, an anti-CD79b conjugated to the microtubule inhibitor monomethyl auristatin E (MMAE) raises particular interest.
We discuss here polatuzumab vedotin development, challenges of designing a successful ADC, preclinical studies and recent trials, leading to FDA approval and the ongoing phase III POLARIX trial.
Clinical data from early studies hold promises for polatuzumab vedotin in association with rituximab-bendamustine in relapsed or refractory (R/R) DLBCL and other combinations are investigated in this setting. In first line, with rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHP), promising results lead to develop the phase III POLARIX trial that may represent a new advance for untreated patients. If dosing and scheduling are adequately managed to avoid peripheral neuropathy risk, polatuzumab vedotin might become a key component of DLBCL therapeutic management. This antibody drug conjugate also offers new opportunities of combination with non-cytotoxic agents or immunological interventions that might reshape the treatment of DLBCL in the future.
需要新的药物来治疗 B 细胞非霍奇金淋巴瘤（NHL），尤其是高危和复发/难治性患者。抗体药物偶联物（ADC）为肿瘤提供靶向药物递送，扩大细胞毒性药物的治疗指数，降低其全身毒性，同时增加细胞内浓度。抗 CD79b 的抗体药物偶联物 polatuzumab vedotin 与微管抑制剂单甲基奥瑞他汀 E（MMAE）偶联，引起了特别的关注。
我们在此讨论了 polatuzumab vedotin 的研发，设计成功的 ADC 所面临的挑战，临床前研究和最近的临床试验，最终获得了 FDA 的批准，并正在进行 III 期 POLARIX 试验。
早期研究的临床数据表明，polatuzumab vedotin 联合利妥昔单抗-苯达莫司汀治疗复发/难治性（R/R）弥漫性大 B 细胞淋巴瘤（DLBCL）及其他联合方案具有广阔的前景。在一线治疗中，联合利妥昔单抗、环磷酰胺、多柔比星和泼尼松（R-CHP），有前景的结果促使开展了 III 期 POLARIX 试验，这可能是未治疗患者的新进展。如果剂量和方案得到适当管理以避免外周神经病变风险，polatuzumab vedotin 可能成为 DLBCL 治疗管理的关键组成部分。这种抗体药物偶联物也为与非细胞毒性药物或免疫干预的联合提供了新的机会，这可能会改变未来 DLBCL 的治疗模式。
