University of Washington.
Fred Hutchinson Cancer Research Center, and.
J Natl Compr Canc Netw. 2022 Apr;20(4):406-416.e11. doi: 10.6004/jnccn.2022.7009.
Chronic immunosuppression in solid organ transplant recipients (SOTRs) leads to an increased risk of a wide variety of cancers. Immune checkpoint inhibitor (ICI) therapy is indicated for many of these; however, the risks and benefits of ICI use in the SOTR population have not been well characterized. We performed a systematic literature review identifying 119 reported cases of ICI use among SOTRs. Treatments used included PD-1 inhibition (75.6%), CTLA-4 inhibition (12.6%), PD-L1 inhibition (1.7%), and combination and/or sequential ICI therapy (10.1%). The most common cancers included cutaneous melanoma (35.3%), hepatocellular carcinoma (22.7%), and cutaneous squamous cell carcinoma (18.5%). The overall objective response rate (ORR) was 34.5%, with a median duration of response of 8.0 months. Ongoing response was seen in 21.0%. Cutaneous squamous cell carcinoma had significantly better ORR compared with other cancer types (68.2% vs 26.8%; odds ratio [OR], 5.85; P =.0006). Factors associated with improved ORR included increasing time from transplant to ICI (OR, 1.09; P =.008) and preemptive reduction in intensity of the graft maintenance immunosuppressive regimen (50.0% vs 18.5%; OR, 4.40; P =.0088). Rejection occurred in 41.2%, graft failure in 23.5%, and immune-related adverse events in 18.5%. Factors significantly associated with allograft rejection included allograft PD-L1 positivity (100% vs 0%; P<.0001) and absence of tacrolimus in the immunosuppressive regimen (48.7% vs 25.6%; OR, 0.36; P =.019). The most common cause of death was progressive malignancy (64.0%), followed by graft failure (24.0%). Our analysis provides current benchmark data to help inform management of SOTRs with advanced cancers that are reflected by our patient cohort. Biomarker development, more robust datasets, and prospective study of concomitant immunosuppression management may help refine decision-making in this complex scenario in the future. Close coordination of care between the medical oncologist and transplant specialist is encouraged to help optimize treatment outcomes.
实体器官移植受者（SOTR）的慢性免疫抑制会导致多种癌症的风险增加。免疫检查点抑制剂（ICI）治疗适用于其中许多癌症；然而，ICI 在 SOTR 人群中的风险和益处尚未得到充分描述。我们进行了系统的文献回顾，确定了 119 例 SOTR 使用 ICI 的报告病例。使用的治疗方法包括 PD-1 抑制（75.6%）、CTLA-4 抑制（12.6%）、PD-L1 抑制（1.7%）以及联合和/或序贯 ICI 治疗（10.1%）。最常见的癌症包括皮肤黑色素瘤（35.3%）、肝细胞癌（22.7%）和皮肤鳞状细胞癌（18.5%）。总体客观缓解率（ORR）为 34.5%，中位缓解持续时间为 8.0 个月。持续缓解率为 21.0%。与其他癌症类型相比，皮肤鳞状细胞癌的 ORR 显著更好（68.2% vs 26.8%；比值比[OR]，5.85；P =.0006）。与改善 ORR 相关的因素包括从移植到 ICI 的时间增加（OR，1.09；P =.008）和预先减少移植物维持免疫抑制方案的强度（50.0% vs 18.5%；OR，4.40；P =.0088）。41.2%的患者发生排斥反应，23.5%的患者发生移植物失功，18.5%的患者发生免疫相关不良事件。与移植物排斥反应显著相关的因素包括移植物 PD-L1 阳性（100% vs 0%；P<.0001）和免疫抑制方案中无他克莫司（48.7% vs 25.6%；OR，0.36；P =.019）。死亡的最常见原因是进展性恶性肿瘤（64.0%），其次是移植物失功（24.0%）。我们的分析提供了当前的基准数据，以帮助为晚期癌症的 SOTR 提供管理信息，这反映在我们的患者队列中。生物标志物的开发、更强大的数据集和对伴随免疫抑制管理的前瞻性研究可能有助于在未来进一步完善这种复杂情况下的决策。鼓励医学肿瘤学家和移植专家之间密切协调护理，以帮助优化治疗结果。
