Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania Health System, Philadelphia.
Department of Radiology, University of Pennsylvania Health System, Philadelphia.
JAMA Netw Open. 2023 Mar 1;6(3):e232526. doi: 10.1001/jamanetworkopen.2023.2526.
Diffuse malignant peritoneal mesothelioma (DMPM) represents a rare and clinically distinct entity among malignant mesotheliomas. Pembrolizumab has activity in diffuse pleural mesothelioma but limited data are available for DMPM; thus, DMPM-specific outcome data are needed.
To evaluate outcomes after the initiation of pembrolizumab monotherapy in the treatment of adults with DMPM.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted in 2 tertiary care academic cancer centers (University of Pennsylvania Hospital Abramson Cancer Center and Memorial Sloan Kettering Cancer Center). All patients with DMPM treated between January 1, 2015, and September 1, 2019, were retrospectively identified and followed until January 1, 2021. Statistical analysis was performed between September 2021 and February 2022.
Pembrolizumab (200 mg or 2 mg/kg every 21 days).
Median progression-free survival (PFS) and median overall survival (OS) were assessed using Kaplan-Meier estimates. The best overall response was determined using RECIST (Response Evaluation Criteria in Solid Tumors) criteria, version 1.1. The association of disease characteristics with partial response was evaluated using the Fisher exact test.
This study included 24 patients with DMPM who received pembrolizumab monotherapy. Patients had a median age of 62 years (IQR, 52.4-70.6 years); 14 (58.3%) were women, 18 (75.0%) had epithelioid histology, and most (19 [79.2%]) were White. A total of 23 patients (95.8%) received systemic chemotherapy prior to pembrolizumab, and the median number of lines of prior therapy was 2 (range, 0-6 lines). Of the 17 patients who underwent programmed death ligand 1 (PD-L1) testing, 6 (35.3%) had positive tumor PD-L1 expression (range, 1.0%-80.0%). Of the 19 evaluable patients, 4 (21.0%) had a partial response (overall response rate, 21.1% [95% CI, 6.1%-46.6%]), 10 (52.6%) had stable disease, and 5 (26.3%) had progressive disease (5 of 24 patients [20.8%] were lost to follow-up). There was no association between a partial response and the presence of a BAP1 alteration, PD-L1 positivity, or nonepithelioid histology. With a median follow-up of 29.2 (95% CI, 19.3 to not available [NA]) months, the median PFS was 4.9 (95% CI, 2.8-13.3) months and the median OS was 20.9 (95% CI, 10.0 to NA) months from pembrolizumab initiation. Three patients (12.5%) experienced PFS of more than 2 years. Among patients with nonepithelioid vs epithelioid histology, there was a numeric advantage in median PFS (11.5 [95% CI, 2.8 to NA] vs 4.0 [95% CI, 2.8-8.8] months) and median OS (31.8 [95% CI, 8.3 to NA] vs 17.5 [95% CI, 10.0 to NA] months); however, this did not reach statistical significance.
The results of this retrospective dual-center cohort study of patients with DMPM suggest that pembrolizumab had clinical activity regardless of PD-L1 status or histology, although patients with nonepithelioid histology may have experienced additional clinical benefit. The partial response rate of 21.0% and median OS of 20.9 months in this cohort with 75.0% epithelioid histology warrants further investigation to identify those most likely to respond to immunotherapy.
弥漫性恶性腹膜间皮瘤（DMPM）是恶性间皮瘤中一种罕见且具有独特临床特征的实体瘤。派姆单抗在弥漫性胸膜间皮瘤中具有活性，但在 DMPM 中可用的数据有限；因此，需要 DMPM 特异性的结果数据。
评估在宾夕法尼亚大学医院 Abramson 癌症中心和纪念斯隆凯特琳癌症中心的 2 个三级癌症护理学术中心接受派姆单抗单药治疗的成人 DMPM 患者的治疗结局。
设计、设置和参与者：这项回顾性队列研究在宾夕法尼亚大学医院 Abramson 癌症中心和纪念斯隆凯特琳癌症中心进行。回顾性确定了 2015 年 1 月 1 日至 2019 年 9 月 1 日期间接受 DMPM 治疗的所有患者，并随访至 2021 年 1 月 1 日。统计分析于 2021 年 9 月至 2022 年 2 月进行。
派姆单抗（200 mg 或 2 mg/kg，每 21 天）。
采用 Kaplan-Meier 估计法评估中位无进展生存期（PFS）和中位总生存期（OS）。使用 RECIST（实体瘤反应评估标准）标准 1.1 确定最佳总体反应。使用 Fisher 精确检验评估疾病特征与部分缓解的关系。
这项研究包括 24 名接受派姆单抗单药治疗的 DMPM 患者。患者的中位年龄为 62 岁（IQR，52.4-70.6 岁）；14 名（58.3%）为女性，18 名（75.0%）为上皮样组织学，大多数（19 名[79.2%]）为白人。23 名患者（95.8%）在接受派姆单抗治疗前接受了全身化疗，中位治疗线数为 2 线（范围，0-6 线）。在 17 名接受程序性死亡配体 1（PD-L1）检测的患者中，6 名（35.3%）肿瘤 PD-L1 表达阳性（范围，1.0%-80.0%）。在 19 名可评估的患者中，4 名（21.0%）有部分缓解（总体缓解率，21.1%[95%CI，6.1%-46.6%]），10 名（52.6%）病情稳定，5 名（26.3%）疾病进展（24 名患者中有 5 名[20.8%]失访）。部分缓解与 BAP1 改变、PD-L1 阳性或非上皮样组织学之间没有关联。中位随访 29.2 个月（95%CI，19.3-无），中位 PFS 为 4.9 个月（95%CI，2.8-13.3），中位 OS 为 20.9 个月（95%CI，10.0-无），从派姆单抗开始治疗。3 名患者（12.5%）的 PFS 超过 2 年。在非上皮样组织学与上皮样组织学患者中，中位 PFS（11.5[95%CI，2.8-无]与 4.0[95%CI，2.8-8.8]个月）和中位 OS（31.8[95%CI，8.3-无]与 17.5[95%CI，10.0-无]个月）存在数值优势；然而，这并没有达到统计学意义。
这项对宾夕法尼亚大学医院 Abramson 癌症中心和纪念斯隆凯特琳癌症中心的 DMPM 患者的回顾性双中心队列研究结果表明，派姆单抗具有临床活性，无论 PD-L1 状态或组织学如何，尽管非上皮样组织学患者可能具有额外的临床获益。在这组 75.0%为上皮样组织学的患者中，部分缓解率为 21.0%，中位 OS 为 20.9 个月，这表明需要进一步研究以确定最有可能对免疫治疗有反应的患者。
