Efficacy of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma in Patients with Concomitant Chronic Lymphocytic Leukemia.
Efficacy of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma in Patients with Concomitant Chronic Lymphocytic Leukemia.
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DOI：
10.1016/j.annonc.2023.06.007
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发表时间：
2023-07
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通讯作者：
S. Cass;J. Tobin;Y. D. Seo;G. Gener-Ricos;E. Keung;E. Burton;M. Davies;J. McQuade;A. Lazar;R. Mason;M. Millward;S. Sandhu;C. Khoo;L. Warburton;V. Guerra;A. Haydon;H. Dearden;A. Menzies;M. Carlino;J. Smith;P. Mollee;M. Burgess;S. Mapp;C. Keane;V. Atkinson;S. Parikh;S. Markovic;W. Ding;T. Call;P. Hampel;G. Long;J. Wargo;A. Ferrajoli
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作者：
S. Cass;J. Tobin;Y. D. Seo;G. Gener-Ricos;E. Keung;E. Burton;M. Davies;J. McQuade;A. Lazar;R. Mason;M. Millward;S. Sandhu;C. Khoo;L. Warburton;V. Guerra;A. Haydon;H. Dearden;A. Menzies;M. Carlino;J. Smith;P. Mollee;M. Burgess;S. Mapp;C. Keane;V. Atkinson;S. Parikh;S. Markovic;W. Ding;T. Call;P. Hampel;G. Long;J. Wargo;A. Ferrajoli
背景免疫检查点抑制剂（ICIs）彻底改变了晚期黑色素瘤（AM）的治疗。然而，关于 ICI 有效性的数据很大程度上仅限于临床试验，因此排除了合并恶性肿瘤的患者。慢性淋巴细胞白血病（CLL）是最常见的成人白血病，与黑色素瘤的风险增加有关。 CLL 会改变全身免疫力，并可诱导 T 细胞耗竭，这可能会限制 ICI 对 CLL 患者的疗效。因此，我们试图检查 ICI 对这些同时发生的诊断的患者的疗效。患者和方法在这项国际多中心研究中，对临床数据库进行回顾性审查，确定了同时诊断为 CLL 和 AM 并接受 ICI 治疗的患者（美国 MD 安德森癌症中心，N = 24；美国梅奥诊所，N = 15；澳大利亚，N = 19）。评估了 CLL 和 AM 患者的客观缓解率 (ORR)（按 RECIST v1.1 评估）和生存结果 [总生存期 (OS) 和无进展生存期 (PFS)]。探讨了与改善 ORR 和生存相关的临床因素。此外，还比较了澳大利亚 CLL/AM 队列和由 148 名仅患有 AM 的澳大利亚患者组成的对照队列之间的 ORR 和生存结果。结果 1997 年至 2020 年间，58 名同时患有 CLL 和 AM 的患者接受了 ICI 治疗。 AUS-CLL/AM 和 AM 对照队列之间的 ORR 相当（53% 对比 48%，P = 0.81）。 ICI 启动后的 PFS 和 OS 在队列之间也具有可比性。在 CLL/AM 患者中，大多数 (64%) 在 ICI 时未接受 CLL 治疗。既往接受过 CLL 化学免疫治疗史的患者 (19%) 的 ORR、PFS 和 OS 显着降低。 结论 我们的并发 CLL 和黑色素瘤患者的病例系列显示出对 ICI 频繁、持久的临床反应。然而，那些先前接受过化学免疫疗法治疗 CLL 的患者的结果明显较差。我们发现 ICI 治疗后 CLL 病程在很大程度上没有改变。
BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses.Patients and methodsIn this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center,N= 24; US-Mayo Clinic,N= 15; AUS,N= 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone.ResultsBetween 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%,P= 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS.ConclusionsOur case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.