Sukari Ammar, Nagasaka Misako, Alhasan Roba, Patel Dhaval, Wozniak Antoinette, Ramchandren Radhakrishnan, Vaishampayan Ulka, Weise Amy, Flaherty Lawrence, Jang Hyejeong, Kim Seongho, Gadgeel Shirish
Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, U.S.A.
Department of Advanced Medical Innovation, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
Anticancer Res. 2019 Feb;39(2):781-790. doi: 10.21873/anticanres.13175.
Data on the characteristics of patients who are likely to experience adverse events, both immune-related and non-immune-related, from programmed cell death-1 (PD1) inhibitors are limited.
Data from patients who received ≥1 dose of single-agent PD1 inhibitor between August 3, 2011 and August 31, 2016 were obtained from our Institution's pharmacy database. AEs were graded using Common Terminology Criteria for Adverse Events version 4.
One hundred and eighty-two patients received at least one dose of single-agent PD1 inhibitor prior to data cut-off. After excluding 14 patients with uncommon malignancies, the total number of patients were 168. The median age was 63 (range=24-92) years. There were 87 (52%) cases of non-small cell lung cancer (NSCLC), 35 (21%) of renal cell carcinoma (RCC), 12 (7%) of melanoma, 18 (11%) of Hodgkin's lymphomas, eight (5%) of head and neck squamous cell carcinoma (HNSCC) and eight (5%) of small cell lung cancer. Considering grade 2 or more AEs, 30 (18%) patients had kidney injury, 34 (20%) hypothyroidism, 36 (21%) transaminitis, 20 (12%) pneumonitis, and 18 (11%) colitis. Patients with RCC had higher odds of experiencing grade 2 or more kidney injury than patients with other primary tumor types (adjusted p=0.025), whereas patients with Hodgkin's lymphoma and HNSCC had higher odds of grade 2 hypothyroidism (adjusted p=0.005). Patients with NSCLC had higher risk of death with pneumonitis than those whose primary cancer was not NSCLC (adjusted p=0.005).
The increased odds of patients with Hodgkin's lymphoma and HNSCC experiencing grade 2 or more hypothyroidism may be related to previous radiation exposure. Most patients with RCC had undergone nephrectomy, making them more susceptible to acute kidney injury. When pneumonitis occurred in patients with primary NSCLC, the overall survival was significantly worse. The duration of PD1 therapy was significantly associated with onset of pneumonitis (p=0.007).
The site of primary tumor or metastasis may help predict the most common AEs in patients treated with PD1 inhibitors.
关于可能经历程序性细胞死亡蛋白1（PD1）抑制剂免疫相关和非免疫相关不良事件的患者特征的数据有限。
从我们机构的药房数据库中获取2011年8月3日至2016年8月31日期间接受≥1剂单药PD1抑制剂治疗的患者数据。使用不良事件通用术语标准第4版对不良事件进行分级。
在数据截止前，182例患者接受了至少一剂单药PD1抑制剂治疗。排除14例患有罕见恶性肿瘤的患者后，患者总数为168例。中位年龄为63岁（范围=24 - 92岁）。其中非小细胞肺癌（NSCLC）87例（52%），肾细胞癌（RCC）35例（21%），黑色素瘤12例（7%），霍奇金淋巴瘤18例（11%），头颈部鳞状细胞癌（HNSCC）8例（5%），小细胞肺癌8例（5%）。考虑2级或更高级别的不良事件，30例（18%）患者出现肾损伤，34例（20%）出现甲状腺功能减退，36例（21%）出现转氨酶升高，20例（12%）出现肺炎，18例（11%）出现结肠炎。与其他原发性肿瘤类型的患者相比，RCC患者发生2级或更高级别肾损伤的几率更高（校正p = 0.025），而霍奇金淋巴瘤和HNSCC患者发生2级甲状腺功能减退的几率更高（校正p = 0.005）。原发性NSCLC患者发生肺炎导致死亡的风险高于原发性癌症不是NSCLC的患者（校正p = 0.005）。
霍奇金淋巴瘤和HNSCC患者发生2级或更高级别甲状腺功能减退的几率增加可能与既往放疗有关。大多数RCC患者接受了肾切除术，使其更容易发生急性肾损伤。原发性NSCLC患者发生肺炎时，总生存期明显更差。PD1治疗持续时间与肺炎的发生显著相关（p = 0.007）。
原发性肿瘤或转移部位可能有助于预测接受PD1抑制剂治疗患者中最常见的不良事件。
