Uemura Marc, Trinh Van A, Haymaker Cara, Jackson Natalie, Kim Dae Won, Allison James P, Sharma Padmanee, Vence Luis, Bernatchez Chantale, Hwu Patrick, Diab Adi
DDepartment of Melanoma Medical Oncology, University of Texas-MD Anderson Cancer Center, 1515 Holcolmbe Blvd., Houston, TX, 77030, USA.
Department of Immunology, University of Texas-MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
J Hematol Oncol. 2016 Sep 5;9(1):81. doi: 10.1186/s13045-016-0309-7.
Novel immunotherapies, or checkpoint inhibitors, targeting programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) have significantly improved outcomes for patients with numerous different cancer types. However, owing to their exclusion from clinical trials and risk for autoimmune exacerbation on these treatments, the impact on safety and degree of toxicity of these potentially life-prolonging therapies is not well characterized in patients with an underlying autoimmune disease or previous organ transplant.
We report a case of a patient with advanced melanoma and refractory Crohn's disease who was treated concurrently with pembrolizumab (anti-PD-1 antibody) and tocilizumab (anti-interluekin-6 receptor antibody). This novel treatment strategy was well tolerated and did not result in Crohn's disease exacerbation for at least 16 weeks. Importantly, this treatment resulted in marked, durable antitumor responses.
This outcome suggests that targeted immunosuppression combined with checkpoint inhibitors may hold promise as a treatment strategy for this unique patient population and may warrant additional study.
针对程序性细胞死亡蛋白-1(PD-1)和细胞毒性T淋巴细胞相关抗原4(CTLA-4)的新型免疫疗法(即检查点抑制剂)已显著改善了多种不同癌症类型患者的治疗结果。然而,由于自身免疫性疾病患者或既往器官移植患者被排除在临床试验之外,且这些治疗存在自身免疫加重的风险,因此这些可能延长生命的疗法对安全性和毒性程度的影响在这类患者中尚未得到充分描述。
我们报告了1例晚期黑色素瘤合并难治性克罗恩病患者,该患者同时接受帕博利珠单抗(抗PD-1抗体)和托珠单抗(抗白细胞介素-6受体抗体)治疗。这种新型治疗策略耐受性良好,至少16周未导致克罗恩病加重。重要的是,该治疗产生了显著、持久的抗肿瘤反应。
这一结果表明,靶向免疫抑制联合检查点抑制剂作为这一特殊患者群体的治疗策略可能具有前景,值得进一步研究。