Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis.
Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis.
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免疫治疗每日输注时间对转移性肾细胞癌患者生存和免疫相关性的影响：多中心队列分析。
DOI：
10.1136/jitc-2023-008011
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发表时间：
2024
影响因子：
10.9
通讯作者：
Qian,Da
中科院分区：
文献类型：
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作者：
Patel,JimmyS;Woo,Yena;Draper,Amber;Jansen,CarolineS;Carlisle,JenniferW;Innominato,PasqualeF;Lévi,FrancisA;Dhabaan,Layla;Master,VirajA;Bilen,MehmetA;Khan,MohammadK;Lowe,MichaelC;Kissick,Haydn;Buchwald,ZacharyS;Qian,Da
背景最近的研究表明，在转移性黑色素瘤和非小细胞肺癌患者中，较早输注免疫检查点抑制剂（ICIs）与较长的无进展生存期（PFS）和总生存期（OS）相关。这些数据与越来越多的临床前证据相一致，即适应性免疫反应可能在当天早些时候得到更有效的刺激。我们试图确定每日不同时间 ICI 输注对转移性肾细胞癌 (mRCC) 患者预后的影响。方法回顾 2015 年至 2020 年间在多中心学术医院系统内开始 ICI 治疗的所有 IV 期 RCC 患者的治疗记录。使用单变量和多变量 Cox 比例风险回归评估中午之前进行的 ICI 输注比例（表示早晨输注）与 PFS 和 OS 之间的关联。结果 在这项研究中，201 名 mRCC 患者（28% 为女性）接受了 ICI 治疗，并接受了中位 18 个月的随访（IQR 5-30）。开始 ICI 时的中位年龄为 63 岁（IQR 56-70）。 101 名患者 (50%) 在中午之前接受了 ≥20% 的 ICI 输注（A 组），100 名患者 (50%) 在中午之前接受了 <20% 的输注（B 组）。在两个比较组中，初始 ICI 药物包括纳武单抗 (58%)、纳武单抗加伊匹单抗 (34%) 和派姆单抗 (8%)。单变量分析显示，与 B 组相比，A 组患者的 PFS 和 OS 更长（PFS HR 0.67，95%CI 0.48 至 0.94，Punivar=0.020；OS HR 0.57，95%CI 0.34 至 0.95，Punivar=0.033）。对年龄、性别、体能状态、国际转移性肾细胞癌数据库联盟风险评分、治疗前乳酸脱氢酶、组织学以及骨、脑和肝转移的存在进行多变量调整后，这些显着的发现仍然存在（PFS HR 0.70，95%CI 0.50 至 0.98，Pmultivar=0.040；OS HR 0.57，95%CI 0.33 至0.98，Pmultivar=0.043）。结论 转移性肾细胞癌 (mRCC) 患者可能会受益于较早接受 ICI。我们的研究结果与时间免疫学的既定机制以及之前黑色素瘤和肺癌的类似研究一致。需要进行额外的前瞻性随机试验。
Background Recent studies have demonstrated that earlier time-of-day infusion of immune checkpoint inhibitors (ICIs) is associated with longer progression-free survival (PFS) and overall survival (OS) among patients with metastatic melanoma and non-small cell lung cancer. These data are in line with growing preclinical evidence that the adaptive immune response may be more effectively stimulated earlier in the day. We sought to determine the impact of time-of-day ICI infusions on outcomes among patients with metastatic renal cell carcinoma (mRCC). Methods The treatment records of all patients with stage IV RCC who began ICI therapy within a multicenter academic hospital system between 2015 and 2020 were reviewed. The associations between the proportion of ICI infusions administered prior to noon (denoting morning infusions) and PFS and OS were evaluated using univariate and multivariable Cox proportional hazards regression. Results In this study, 201 patients with mRCC (28% women) received ICIs and were followed over a median of 18 months (IQR 5–30). The median age at the time of ICI initiation was 63 years (IQR 56–70). 101 patients (50%) received ≥20% of their ICI infusions prior to noon (Group A) and 100 patients (50%) received <20% of infusions prior to noon (Group B). Across the two comparison groups, initial ICI agents consisted of nivolumab (58%), nivolumab plus ipilimumab (34%), and pembrolizumab (8%). On univariate analysis, patients in Group A had longer PFS and OS compared with those in Group B (PFS HR 0.67, 95% CI 0.48 to 0.94, Punivar=0.020; OS HR 0.57, 95% CI 0.34 to 0.95, Punivar=0.033). These significant findings persisted following multivariable adjustment for age, sex, performance status, International Metastatic RCC Database Consortium risk score, pretreatment lactate dehydrogenase, histology, and presence of bone, brain, and liver metastases (PFS HR 0.70, 95% CI 0.50 to 0.98, Pmultivar=0.040; OS HR 0.57, 95% CI 0.33 to 0.98, Pmultivar=0.043). Conclusions Patients with mRCC may benefit from earlier time-of-day receipt of ICIs. Our findings are consistent with established mechanisms of chrono-immunology, as well as with preceding analogous studies in melanoma and lung cancer. Additional prospective randomized trials are warranted.