Department of Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Front Immunol. 2020 Nov 6;11:563622. doi: 10.3389/fimmu.2020.563622. eCollection 2020.
In murine cancer models, B cells are unnecessary for efficacy of PD-1 inhibitor. However, we do not know whether this applies to clinical settings, especially in patients with non-small-cell lung carcinoma (NSCLC).
We report on the case of an advanced lung adenocarcinoma patient without oncogenic driver mutations whose disease progressed on second-line bevacizumab-containing chemotherapy regimens. These previous treatments resulted in profound thrombocytopenia and increased number of B cells; both effects were hard to alleviate. The patient was diagnosed with marginal zone B-cell lymphoma by flow cytometry immunophenotyping. After five cycles of rituximab in combination with lenalidomide treatment, the percentage of B cells rapidly declined to undetectable levels and the lymphoma regressed completely. However, because masses in the lung gradually increased, this patient was subsequently treated with a PD-1 inhibitor. The patient's condition stabilized, and the mass shrank to reach partial response, with progression free survival exceeding 15 months and no serious adverse events.
The present case proves the efficacy of PD-1 inhibitor in metastatic lung adenocarcinoma in the absence of B cells. Immune checkpoint inhibitions are thus a choice for patients with B cell deficiencies, such as X-linked agammaglobulinemia, immunoglobulin deficiencies, and common variable immunodeficiency, diseases that have historically been excluded from clinical trials for oncologic drugs.
在鼠类癌症模型中，B 细胞对于 PD-1 抑制剂的疗效并非必需。然而，我们尚不清楚这一结论是否适用于临床环境，尤其是非小细胞肺癌（NSCLC）患者。
我们报告了一例晚期肺腺癌患者的病例，该患者无致癌驱动基因突变，二线含贝伐珠单抗的化疗方案治疗后疾病进展。这些既往治疗导致严重的血小板减少和 B 细胞数量增加，这两种情况都难以缓解。流式细胞术免疫表型分析诊断该患者患有边缘区 B 细胞淋巴瘤。接受利妥昔单抗联合来那度胺治疗五个周期后，B 细胞的比例迅速降至无法检测的水平，淋巴瘤完全消退。然而，由于肺部肿块逐渐增大，该患者随后接受了 PD-1 抑制剂治疗。患者病情稳定，肿块缩小至部分缓解，无进展生存期超过 15 个月，且无严重不良事件。
本病例证明了 PD-1 抑制剂在无 B 细胞的转移性肺腺癌中的疗效。因此，对于 X 连锁无丙种球蛋白血症、免疫球蛋白缺乏症和常见可变免疫缺陷等 B 细胞缺陷患者，免疫检查点抑制剂是一种选择，这些疾病在过去曾被排除在肿瘤药物临床试验之外。
