National Institute for Health Research University College London Hospitals Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK.
Am J Hematol. 2023 Mar;98 Suppl 2:S22-S34. doi: 10.1002/ajh.26750. Epub 2022 Oct 24.
The treatment landscape of multiple myeloma (MM) has evolved substantially, but it remains largely incurable so new treatment options are required. Antibody drug conjugates (ADCs) are an emerging therapeutic class used in Cancer to deliver targeted therapy. ADCs are composed of three components, an antibody, a chemical linker and a payload which must be chosen carefully to be effective and safe. This alternative mechanism of action to standard treatments makes ADCs an attractive class for further development. However, several ADCs have been investigated but many have not moved further than phase 1 trials, highlighting the challenges in designing an effective and tolerable ADC. Belantamab Mafodotin is currently the only ADC licensed for MM although others are currently under evaluation. Belantamab Mafodotin demonstrated efficacy as monotherapy in triple class exposed patients and combinations are under development which maintain safety with encouraging efficacy particularly at earlier lines of therapy. Retaining an acceptable adverse event profile for ADCs remains vital for their success. Strategies to mitigate ocular events for Belantamab Mafodotin involve lower and less frequent dosing as well as the use of gamma secretase inhibitors. The optimal sequencing of ADCs within the treatment pathway including novel immunotherapies is now under evaluation.
多发性骨髓瘤（MM）的治疗格局已经发生了重大变化，但该病仍然基本上无法治愈，因此需要新的治疗选择。抗体药物偶联物（ADC）是一种新兴的治疗类别，用于癌症的靶向治疗。ADC 由三个组成部分组成，抗体、化学连接子和有效载荷，必须仔细选择以确保其有效和安全。与标准治疗方法相比，这种作用机制的替代方法使 ADC 成为进一步开发的一个有吸引力的类别。然而，已经研究了几种 ADC，但许多都没有超过 1 期临床试验，这突显了设计有效和耐受的 ADC 的挑战。Belantamab Mafodotin 是目前唯一获准用于 MM 的 ADC，尽管其他 ADC 目前正在评估中。Belantamab Mafodotin 作为三线暴露患者的单药治疗显示出疗效，正在开发联合治疗方案，这些方案在早期治疗中保持安全性和令人鼓舞的疗效。对于 ADC 而言，保持可接受的不良事件谱对于其成功仍然至关重要。降低和减少 Belantamab Mafodotin 的眼部事件的策略包括降低剂量和减少用药频率，以及使用γ分泌酶抑制剂。ADC 在治疗途径中的最佳排序，包括新型免疫疗法，目前正在评估中。
