Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Burning Rock Biotech, Guangzhou, China.
Medicine (Baltimore). 2023 Jan 20;102(3):e32508. doi: 10.1097/MD.0000000000032508.
Membranous nephropathy (MN) is an autoimmune disease, which is classified into primary and secondary MN. Malignancy-associated MN (M-MN) accounts for about 10% of secondary MN cases. Lung cancer is the most common type of malignancy among M-MN patients. Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) have showed promising efficacy and good safety in many types of solid tumors, including non-small cell lung cancer. To date, whether ICIs could be a treatment option for M-MN patients with PD-L1 expression and or high tumor mutation burden (TMB) level has not been documented.
A 68-year-old male patient presented with edema of the lower limbs with increased urine foam in August 2018. Biopsy on the right kidney showed MN at stage I with subepithelially localized immune deposits.
Lung squamous cell carcinoma (LSCC)-associated MN with PD-L1 expression (20%) and high TMB level (26.2 mutations/Mb).
The patient received immunosuppressive therapy targeting the initially diagnosed primary MN as first-line treatment plus surgery and radiochemotherapy following pembrolizumab targeting the definitively diagnosed lung cancer as second-line treatment.
The patient benefited from radiochemotherapy following pembrolizumab (lasting more than 38 months) rather than immunosuppressive therapy.
Our work suggests that combined ICIs might be an effective treatment option for M-MN patients who harbor PD-L1 expression. Our work highlights that the presence of malignancy should not be neglected at the initial diagnosis of MN.
膜性肾病(MN)是一种自身免疫性疾病,可分为原发性和继发性 MN。恶性肿瘤相关性 MN(M-MN)约占继发性 MN 病例的 10%。肺癌是 M-MN 患者中最常见的恶性肿瘤类型。针对程序性细胞死亡受体 1(PD-1)或程序性细胞死亡配体 1(PD-L1)的免疫检查点抑制剂(ICI)在包括非小细胞肺癌在内的多种实体瘤中显示出有前景的疗效和良好的安全性。迄今为止,针对 PD-L1 表达和/或高肿瘤突变负荷(TMB)水平的 M-MN 患者,ICI 是否可以作为一种治疗选择尚未有相关报道。
一名 68 岁男性患者于 2018 年 8 月出现下肢水肿伴尿液泡沫增多。右肾活检显示 I 期 MN,上皮下有免疫沉积物。
肺鳞状细胞癌(LSCC)相关性 MN,PD-L1 表达(20%),TMB 水平高(26.2 突变/Mb)。
患者接受了针对最初诊断的原发性 MN 的一线治疗(免疫抑制治疗),随后接受了针对明确诊断的肺癌的二线治疗(帕博利珠单抗)。
患者从帕博利珠单抗的放化疗中获益(持续 38 个月以上),而不是免疫抑制治疗。
我们的工作表明,联合使用 ICI 可能是治疗 PD-L1 表达的 M-MN 患者的有效治疗选择。我们的工作强调,在 MN 的初始诊断时不应忽视恶性肿瘤的存在。