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病例报告:一例转移性BRAFV600突变黑色素瘤合并心力衰竭患者接受免疫检查点抑制剂和BRAF/MEK抑制剂治疗。

Case report: A case of metastatic BRAFV600-mutated melanoma with heart failure treated with immune checkpoint inhibitors and BRAF/MEK inhibitors.

作者信息

Nishizawa Aya, Kawakami Misaki, Kitahara Yasuyuki

机构信息

Department of Dermatology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.

Department of Cardiology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.

出版信息

Front Oncol. 2024 Mar 11;14:1366532. doi: 10.3389/fonc.2024.1366532. eCollection 2024.

Abstract

BACKGROUND

Novel therapies, immune checkpoint inhibitors (ICIs), and BRAF/MEK inhibitors (BRAFi/MEKi) provide unprecedented survival benefits for patients with advanced melanoma. However, the management of drug-induced adverse events is problematic for both agents and, although rare, can cause serious cardiac dysfunction.

CASE REPORT

A 42-year-old male patient with no significant medical history noticed a fading dark brown patch on his left anterior chest, which had been there for 20 years, after his second coronavirus disease 2019 (COVID-19) vaccination. The left axillary lymph node became swollen one week after a third booster vaccination. Thinking of it as an adverse reaction to the vaccine, but the swelling increased, so he visited a hospital. The patient presented with a brown macule with depigmentation on the left anterior chest and a 13 cm left axillary mass. A biopsy of the axillary mass showed a metastatic malignant melanoma. Positron emission tomography (PET) showed an accumulation only in the axillary lymph nodes. One month after the initial diagnosis, the axillary mass had further enlarged. In addition, pleural effusion, ascites, difficulty breathing, and systemic edema appeared, and he was diagnosed with heart failure (NYHA class III). Echocardiography showed an ejection fraction of 52% and electrocardiogram (ECG) showed no abnormal findings. Though it was (a life-threatening instead of the life-threatening) the life-threatening condition, we determined that the symptoms were associated with the current disease. Then nivolumab (nivo) plus ipilimumab (ipi) was initiated after explaining the risk of cardiac dysfunction associated with drug use to the patient. After initiation of ICIs, treatment was switched to BRAFi/MEKi (encorafenib/vinimetinib) after the patient tested positive for BRAF V600E. After one month of treatment, the tumor shrank significantly and achieved a complete remission after four months. Furthermore, as the tumor shrank, the patient's heart failure improved, and he was able to continue treatment without serious drug-induced cardiotoxicity.

CONCLUSION

Both ICI and BRAFi/MEKi carry a risk of cardiac dysfunction. However, without any underlying cardiac disease or severe cardiac dysfunction, their administration should not necessarily be excluded if careful follow-up is provided.

摘要

背景

新型疗法、免疫检查点抑制剂(ICIs)和BRAF/MEK抑制剂(BRAFi/MEKi)为晚期黑色素瘤患者带来了前所未有的生存益处。然而,这两种药物引起的不良事件管理都存在问题,而且尽管罕见,但可能导致严重的心功能障碍。

病例报告

一名42岁男性患者,无重大病史,在接种第二剂2019冠状病毒病(COVID-19)疫苗后,注意到其左前胸有一块已存在20年的暗褐色斑逐渐变淡。在接种第三剂加强疫苗一周后,左腋窝淋巴结肿大。患者起初认为这是疫苗的不良反应,但肿大情况加剧,于是前往医院就诊。患者左前胸有一块色素脱失的褐色斑,左腋窝有一个13厘米的肿块。腋窝肿块活检显示为转移性恶性黑色素瘤。正电子发射断层扫描(PET)显示仅腋窝淋巴结有放射性浓聚。初诊一个月后,腋窝肿块进一步增大。此外,出现了胸腔积液、腹水、呼吸困难和全身性水肿,患者被诊断为心力衰竭(纽约心脏协会III级)。超声心动图显示射血分数为52%,心电图(ECG)无异常发现。尽管这是一种危及生命而非正在危及生命的情况,但我们确定这些症状与当前疾病有关。然后在向患者解释了药物使用相关的心功能障碍风险后,开始使用纳武单抗(nivo)加伊匹单抗(ipi)。开始使用ICIs治疗后,在患者BRAF V600E检测呈阳性后,治疗改为BRAFi/MEKi(恩考芬尼/维莫非尼)。治疗一个月后,肿瘤显著缩小,四个月后实现完全缓解。此外,随着肿瘤缩小,患者的心力衰竭有所改善,他能够继续治疗而未出现严重的药物性心脏毒性。

结论

ICI和BRAFi/MEKi都有导致心功能障碍的风险。然而,如果进行仔细的随访,在没有任何潜在心脏病或严重心功能障碍的情况下,不一定应排除使用它们。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c59/10961452/5842c6984006/fonc-14-1366532-g001.jpg

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