Treatment with immune checkpoint inhibitors is effective in various cancers, but may be associated with immune-mediated side effects in other organs. Among the more common ones is gastrointestinal tract involvement, especially colitis. In most patients, colitis is mild or responds to corticosteroid treatment. A smaller proportion of patients, more often those treated with cytotoxic T lymphocyte antigen-4 inhibitors, may have a more severe course of colitis, even life-threatening complications. In these patients, prompt action, timely diagnosis with endoscopic evaluation and early treatment with high-dose corticosteroids and, if ineffective, rescue therapy with biologic agents such as infliximab and vedolizumab are needed. We present three cases from our clinical practice, data on incidence and clinical presentation, current recommendations regarding diagnostic approach and treatment of immune checkpoint inhibitors induced colitis.

2024-05-01·AACE clinical case reports

Severe Hyponatremia Triggered by Immune Checkpoint Inhibitor Therapy in a Patient With Mulvihill-Smith Syndrome

作者: Mathias, Priyanka ; Tavdy, Tammy ; Samavedam, Janaki Manasa ; Lee, Hanna J.

Background/Objective:

Immune checkpoint inhibitors (ICI), including Programmed Cell Death 1, Programmed Cell Death Ligand 1, and Cytotoxic T-lymphocyte Associated Antigen 4 inhibitors, upregulate T-cell responses against tumor cells and are becoming a cornerstone in the treatment of various advanced solid and hematological cancers. Mulvihill-Smith Syndrome (MSS) is a rare genetic syndrome that has been associated with metabolic abnormalities and early-onset tumors, including malignancies. We report the first known case of ICI-induced hyponatremia attributable to syndrome of inappropriate antidiuretic hormone ADH release (SIADH) in a patient with MSS.

Case Report:

A 23-year-old female patient with MSS and hepatocellular carcinoma presented with recurrent hyponatremia. Assessment of fluid status and electrolytes revealed a euvolemic, hypotonic process consistent with SIADH shortly after initiating adjuvant therapy with atezolizumab, a Programmed Cell Death Ligand 1 inhibitor.

Discussion:

Endocrine etiologies for euvolemic hypotonic hyponatremia, including adrenal insufficiency and hypothyroidism, were excluded. The diagnosis of SIADH was confirmed based on electrolyte and osmolality studies. Sodium levels normalized with fluid restriction. Given the onset of hyponatremia 30 days after atezolizumab initiation, we posit that atezolizumab triggered severe hyponatremia due to SIADH.

Conclusion:

With the expanding utilization of ICIs, including in patients predisposed to malignancies such as MSS, vigilant monitoring for ICI-mediated electrolyte imbalances is crucial. Monitoring for hyponatremia and SIADH in the setting of ICI therapy is recommended.

2024-02-01·Translational andrology and urology

A narrative review of management of muscle-invasive bladder cancer perioperative period: will continuous and combined treatment be the new trend?

Review

作者: Gao, Mingchao ; Ran, Shengming ; Lan, Tianhang ; Li, Wenjie ; He, Wang

Background and Objective:

With the emergence of immunotherapy and targeted therapies, there are more options for the perioperative period management of muscle-invasive bladder cancer (MIBC), and various types of clinical studies are emerging, leading to the need to explore ways to choose the optimal treatment modality. This review aims to synthesize past and present treatment modalities and to explore future trends in the perioperative period cares of MIBC for the benefit of clinical practitioners.

Methods:

A non-systematic, literature search was conducted between March 5, 2023 and November 30, 2023 on PubMed using "perioperative period", "MIBC", "chemotherapy", "radiotherapy", "immunotherapy", "targeted treatment" and "combination" as keywords, along with a search for ongoing clinical studies that were related to the perioperative period of MIBC on classic.clinicaltrials.gov, some latest conference abstracts were also included as references.

Key Content and Findings:

The trend towards benefit from adjuvant chemotherapy in perioperative chemotherapy is gradually being recognized. Neoadjuvant immunotherapy, including single-agent immunization, like programmed cell death protein 1 (PD-1) inhibitors, programmed cell death 1 ligand 1 (PD-L1) inhibitors and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, and double-immunization, has been confirmed by several clinical studies to be beneficial to clinical remission rates, and the combination regimen is superior to single-agent therapy. Targeted therapies such as antibody-drug conjugate (ADC) are entering MIBC perioperative studies. Multiple sequential and combination clinical studies are gradually disclosing preliminary data on efficacy and safety.

Conclusions:

Immunotherapy would become an essential perioperative treatment for MIBC, and continuous and integrated perioperative management may become the MIBC treatment mode of the future. ADC medicines will also be a hot research focus in the coming years.

项与 CTLA-4-XTEN 相关的新闻（医药）

2023-02-17

·信达生物

临床试验 | 信达生物IBI310（抗CTLA-4）联合信迪利单抗治疗晚期胆道癌临床研究进行中

胆道癌胆道癌（Biliary tract cancer，BTC）是继胰腺癌之后的一种罕见的恶性肿瘤，占全球所有癌症的不到1%，预后较差（5年生存率约7-20%），一线治疗后没有全球统一的治疗标准。该肿瘤分为四种类型：肝内胆管癌（intrahepatic cholangiocarcinoma，iCCA）、肝外胆管癌（extrahepatic cholangiocarcinoma，eCCA）、胆囊癌、壶腹癌。全球发病数量的数量约为210,000余人，全球发病率呈上升趋势，亚洲国家最为常见。信达生物制药（苏州）有限公司正在开展一项“IBI310（抗-CTLA-4）联合信迪利单抗用于标准治疗后进展的晚期胆道癌的单臂、多中心、Ib/II期研究”。方案号：CIBI310J201。试验药物简介重组全人源抗细胞毒T淋巴细胞相关抗原4（CTLA-4）单克隆抗体注射液（研发代号：IBI310）是信达生物制药（苏州）有限公司自主研发的一种全人源单克隆抗体。IBI310能特异性结合CTLA-4，从而阻断CTLA-4介导的T细胞抑制，促进T细胞的激活和增殖，提高肿瘤免疫反应，达到抗肿瘤的效果。信迪利单抗为重组全人源IgG4型抗PD-1单克隆抗体注射液（研发代号：IBI308），是信达生物制药（苏州）有限公司自主研发的一种全人源单克隆抗体。2019年2月22日，信迪利单抗正式在中国内地上市，适应症为经典霍奇金淋巴瘤。截止到目前，信迪利单抗已在中国获批6项适应症，包括经典霍奇金淋巴瘤、晚期非鳞状非小细胞肺癌、局部晚期或转移性鳞状非小细胞肺癌、肝细胞癌、晚期食管癌以及晚期胃和胃食管交界处癌。CIBI310J201项目目前正在入组中，招募符合方案所有条件的既往接受过至少1线标准治疗后进展的晚期胆道癌患者。主要入组标准 1. 年龄在18周岁及以上。2. 不可切除或转移性或术后复发、组织学确诊的晚期胆道癌（壶腹癌除外）。3. 既往接受过至少1线系统性治疗后疾病进展。（在辅助治疗阶段接受系统性抗肿瘤治疗的患者在治疗结束后6个月内发生疾病进展的，算作1线治疗）。4. 未接受过抗PD-1/PD-L1单抗、抗CTLA-4等相关免疫治疗。5. 根据RECIST V1.1评估标准，至少有1个可测量病灶；对于既往接受过放疗等局部治疗的病灶，如果根据RECIST V1.1确认进展，可作为靶病灶。研究中心清单中心编号研究中心名称主要研究者联系方式2湖南省肿瘤医院罗嘉罗老师15874093620

临床结果免疫疗法

100 项与 CTLA-4-XTEN 相关的药物交易

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