Abstract B161: Pseudoprogression of metastatic abdominal wall nodules in a patient with lung carcinoma treated with pembrolizumab

T. Hennedige, D. Tan, N. Iyer, Amit L. Jain
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Abstract

Pembrolizumab is a humanized IgG4 Kappa monoclonal programmed death receptor 1 directed antibody FDA approved for the first line treatment of metastatic non-small cell lung carcinoma (NSCLC) expressing >=50% PD-L1. Pseudoprogression in this context has rarely been reported. We encountered a patient within our community practice who received treatment with pembrolizumab and demonstrated radiologic features of pseudoprogression initially followed by clinical progression where upon histologic evaluation favored pseudoprogression over progression. The aims of this study are as follows: Firstly, to describe the clinico-pathologic-radiologic aspects of this patient’s treatment journey; secondly, to histologically characterize a lesion that was biopsied which showed clinical features of progression, but histologically, pseudoprogression; thirdly, to perform detailed flow cytometric analysis of lymphocytes obtained through the biopsy to characterize pseudoprogression. This is a single patient case study performed by reviewing clinical notes, radiology, and histology. Samples obtained on biopsy were further characterized by flow cytometry. A 72-year-old male patient with small volume metastatic squamous cell lung carcinoma with a tumor proportion score of 100% for PD-L1, was initially treated with radiation (20Gy) to palliate worsening dyspnea caused by airway obstruction. He had good local control with improvement in dyspnea and subsequently requested for observation only. Serial imaging revealed the development of an abdominal wall nodule. Before long, his metastatic disease became symptomatic and he was treated with first line pembrolizumab. Three weeks after his first dose, he presented with severe abdominal wall pain and a new palpable abdominal wall mass. Imaging performed confirmed the presence of a new abdominal wall mass in contrast to a reduction in size of his pulmonary lesions. This was thus assessed as pseudoprogression, and he was continued on treatment with radiologic response noted three weeks later in all lesions. He discontinued treatment due to cost at this point, and subsequently restarted treatment upon radiologic progression of disease. On restarting treatment, his abdominal wall nodule increased in size and ulcerated. True tumor progression was considered prompting biopsy of the abdominal wall nodule to enable stratification into clinical trials. However, histologic evaluation showed chronically inflamed granulation tissue with no microscopic evidence of malignancy suggesting pseudoprogression once again instead. The patient went on to receive radiotherapy to the abdominal wall nodule, and a serial scan demonstrated a reduction in size of the abdominal wall nodule and stable pulmonary disease. Flow cytometric analysis of biopsy tissue revealed predominantly CD45+ cells, 69.5% of which were CD3+. CD45+CD3+CD56- cells comprised CD4+ (27.9%), CD8+ (64.9%), CD4+PD1+ (46.7%), CD8+PD+ (37.7%). Further analysis by flow and mass cytometry is ongoing, and attempts are also being made to assess the tumor antigen specificity of the T-cells. In a patient with clinically immunogenic cancer responding to intermittent anti-PD1 therapy, we observed varying clinico-radiologic responses across his metastatic lesions, and a pathologic evaluation of a clinically progressing lesion revealed pseudoprogression instead. Citation Format: Tiffany Hennedige, Daniel Tan, Narayanan Gopalakrishna Iyer, Amit Jain. Pseudoprogression of metastatic abdominal wall nodules in a patient with lung carcinoma treated with pembrolizumab [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B161.
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B161: pembrolizumab治疗的肺癌患者转移性腹壁结节的假进展
Pembrolizumab是一种人源化IgG4 Kappa单克隆程序性死亡受体1定向抗体,FDA批准用于转移性非小细胞肺癌(NSCLC)的一线治疗,表达>=50%的PD-L1。这种情况下的假进展很少有报道。在我们的社区实践中,我们遇到了一位患者,他接受了派姆单抗治疗,最初表现出假进展的放射学特征,随后是临床进展,在组织学评估中,假进展优于进展。本研究的目的如下:首先,描述该患者治疗过程的临床-病理-放射学方面;其次,对活检后表现出进展的临床特征,但在组织学上为假进展的病变进行组织学表征;第三,对活检获得的淋巴细胞进行详细的流式细胞术分析,以表征假性进展。这是通过回顾临床记录、放射学和组织学进行的单个患者病例研究。活检获得的样本通过流式细胞术进一步表征。一例72岁男性小体积转移性鳞状细胞肺癌患者,PD-L1肿瘤比例评分为100%,最初接受放射治疗(20Gy),以缓解气道阻塞引起的呼吸困难恶化。患者局部控制良好,呼吸困难有所改善,随后要求仅留院观察。连续影像显示腹壁结节的发展。不久,他的转移性疾病出现了症状,他接受了一线派姆单抗治疗。第一次服药后三周,患者出现严重的腹壁疼痛和新的可触及的腹壁肿块。影像学检查证实新腹壁肿块的存在,肺部病变缩小。因此,这被评估为假性进展,他继续接受治疗,三周后所有病变都有放射学反应。由于费用原因,他在此时停止了治疗,随后在疾病放射学进展后重新开始治疗。重新开始治疗后,他的腹壁结节增大并溃烂。真正的肿瘤进展被认为是促使腹壁结节活检,使分层进入临床试验。然而,组织学评估显示慢性炎症肉芽组织,没有显微镜证据表明恶性肿瘤再次提示假性进展。患者继续接受腹壁结节放射治疗,连续扫描显示腹壁结节大小缩小,肺部疾病稳定。活检组织的流式细胞术分析显示CD45+细胞为主,CD3+细胞占69.5%。CD45 +细胞CD3 + CD56 -由CD4 +(27.9%)、CD8 +(64.9%)、CD4 + PD1 +(46.7%)、CD8 + PD +(37.7%)。进一步的流式细胞术和大量细胞术分析正在进行中,并试图评估t细胞的肿瘤抗原特异性。在一名对间歇性抗pd1治疗有反应的临床免疫原性癌症患者中,我们观察到他的转移性病灶的临床放射学反应不同,而对临床进展性病灶的病理评估显示为假进展。引用格式:Tiffany Hennedige, Daniel Tan, Narayanan Gopalakrishna Iyer, Amit Jain。pembrolizumab治疗肺癌患者转移性腹壁结节的假进展[摘要]。第四届CRI-CIMT-EATI-AACR国际癌症免疫治疗会议:将科学转化为生存;2018年9月30日至10月3日;纽约,纽约。费城(PA): AACR;癌症免疫学杂志,2019;7(2增刊):摘要nr B161。
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