Department of Pharmacy, Paul Brousse University Hospital, Villejuif, France.
Department of Pharmacy, Troyes General Hospital, Troyes, France.
J Oncol Pharm Pract. 2023 Mar;29(2):479-483. doi: 10.1177/10781552221105572. Epub 2022 Jun 5.
Nivolumab, the monoclonal antibody inhibitor of programmed cell death protein 1, enhances the T-cell response, including anti-tumour responses, by blocking the attachment of programmed death-ligand 1 and programmed death-ligand 2 ligands to the programmed cell death protein 1 receptor, which in turn leads to a reduction in tumour growth. Nivolumab has been approved in relapsed or refractory classic Hodgkin's lymphoma after autologous transplantation of haematopoietic stem cell and treatment with brentuximab as monotherapy.
We herewith report a case of 65-year-old woman who developed an interstitial pneumonitis and a global cardiac hypokinesis following a treatment with Nivolumab for a refractory Hodgkin's Lymphoma. Nivolumab was administered as the fifth line of therapy. Some concomitant patient treatments include drug with known autoimmune toxicities. Although the patient had a persistent complete remission following the sixth infusion, it was discontinued as she developed dyspnea of NYHA stage IV and orthopnea. The chest tomography revealed a bilateral micronodular pattern of organizing pneumonia with bilateral pleural effusion. The forced expiratory volume was decreased to 50%. In parallel her transthoracic echocardiography revealed a global hypokinesis with a left ventricular ejection fraction of 20%.
The patient was treated with empiric antibiotics although the microbial assessments were negative. She was also treated with beta-blocker and angiotensin-converting enzyme inhibitors. The cardiac magnetic resonance imaging performed after 4 months confirmed the hypokinetic cardiopathy with an ejection fraction of 48%. The patient had a significant clinical improvement. The tomography emission positron scan conducted 8 months after interruption of Nivolumab showed complete remission with some moderate activation of residual lesion basal posterior lobe of left lung field.
Early and effective diagnosis of immune-related adverse events through the search for predictive biomarkers like drug factors and individual risk factors will allow targeted surveillance leading to a better tolerance.
纳武利尤单抗是一种程序性细胞死亡蛋白 1 的单克隆抗体抑制剂,通过阻断程序性死亡配体 1 和程序性死亡配体 2 配体与程序性死亡蛋白 1 受体的结合,增强 T 细胞反应,包括抗肿瘤反应,从而导致肿瘤生长减少。纳武利尤单抗已在自体造血干细胞移植后和单药使用 Brentuximab 治疗复发或难治性经典霍奇金淋巴瘤中获得批准。
我们在此报告一例 65 岁女性,在接受纳武利尤单抗治疗难治性霍奇金淋巴瘤后发生间质性肺炎和全心脏运动减退。纳武利尤单抗是作为第五线治疗药物使用。同时还存在一些伴有已知自身免疫毒性的药物治疗。尽管患者在第六次输注后持续完全缓解,但由于出现 NYHA Ⅳ级呼吸困难和端坐呼吸而停止治疗。胸部 CT 显示双侧微结节样机化性肺炎伴双侧胸腔积液。用力呼气量减少到 50%。同时,她的经胸超声心动图显示全心脏运动减退,左心室射血分数为 20%。
尽管微生物评估呈阴性,但患者仍接受了经验性抗生素治疗。她还接受了β受体阻滞剂和血管紧张素转换酶抑制剂治疗。4 个月后进行的心脏磁共振成像证实存在运动减退性心脏病,射血分数为 48%。患者的临床状况显著改善。中断纳武利尤单抗 8 个月后进行的正电子发射断层扫描显示完全缓解,左肺下叶基底后段残留病变有中度活性。
通过寻找药物因素和个体危险因素等预测性生物标志物,早期、有效地诊断免疫相关不良事件,将有助于进行有针对性的监测,从而提高耐受性。