Exceptionally long-lasting response to dabrafenib plus trametinib treatment in a patient with lung adenocarcinoma harboring the BRAF V600E mutation with high expression of PD-L1: A case report.

We present a patient with lung adenocarcinoma showing high PD-L1 expression and BRAF V600E mutation, who achieved a remarkable long-term response to the combination therapy of dabrafenib and trametinib (DT treatment) after disease progression on immunotherapy. This case may provide an opportunity for clinicians to consider the order of administration of immunotherapy and molecular targeted therapy for BRAF V600E-positive lung cancer.

Long-term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the Phase II VISION study.

Tepotinib is a highly selective MET tyrosine kinase inhibitor (TKI) that has demonstrated robust and durable clinical activity in patients with MET exon 14 (METex14) skipping non-small-cell lung cancer (NSCLC). In the Phase II VISION study, patients received oral tepotinib 500 mg once daily. The primary endpoint was an objective response by an independent review committee (IRC) according to RECIST v1.1 criteria. The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Here we report the analysis of the efficacy and safety of tepotinib in all Japanese patients with advanced METex14 skipping NSCLC from VISION (n = 38) with >18 months' follow-up. The median age of the Japanese patients was 73 years (range 63-88), 39.5% of patients were ≥75 years old, 68.4% were male, 55.3% had a history of smoking, 76.3% had adenocarcinoma, and 10.5% of patients had known brain metastases at baseline. Overall, the objective response rate (ORR) was 60.5% (95% confidence interval (CI): 43.4, 76.0) with a median DOR of 18.5 months (95% CI: 8.3, not estimable). ORR in treatment-naïve patients (n = 18) was 77.8% (95% CI: 52.4, 93.6), and in patients aged ≥75 years (n = 15), ORR was 73.3% (95% CI: 44.9, 92.2). The most common treatment-related adverse event (AE) with any grade was blood creatinine increase (65.8%), which resolved following tepotinib discontinuation. Other common treatment-related AEs were peripheral edema (60.5%), hypoalbuminemia (34.2%), diarrhea (28.9%), and nausea (15.8%). In summary, tepotinib demonstrated robust and durable clinical activity irrespective of age or therapy line, with a manageable safety profile in Japanese patients with METex14 skipping NSCLC enrolled in VISION.

Potent CTLs can be induced against tumor cells in an environment of lower levels of systemic MFG-E8.

The direction and magnitude of immune responses are critically affected when dead cells are disposed of. Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) promotes the engulfment of apoptotic normal and cancerous cells without inducing inflammation. We have previously reported that a certain proportion of the cancer cells express abundant MFG-E8, and that such expression is associated with the shorter survival of patients with esophageal cancer who had received chemotherapy before surgery. However, the influence of tumor-derived and systemically existing MFG-E8 on antitumor immune responses has not yet been fully investigated. Herein, we showed that CTL-dependent antitumor immune responses were observed in mice with no or decreased levels of systemic MFG-E8, and that such responses were enhanced further with the administration of anti-PD-1 antibody. In mice with decreased levels of systemic MFG-E8, the dominance of regulatory T cells in tumor-infiltrating lymphocytes was inverted to CD8+ T cell dominance. MFG-E8 expression by tumor cells appears to affect antitumor immune responses only when the level of systemic MFG-E8 is lower than the physiological status. We have also demonstrated in the clinical setting that lower levels of plasma MFG-E8, but not MFG-E8 expression in tumor cells, before the treatment was associated with objective responses to anti-PD-1 therapy in patients with non-small cell lung cancer. These results suggest that systemic MFG-E8 plays a critical role during the immunological initiation process of antigen-presenting cells to increase tumor-specific CTLs. Regulation of the systemic level of MFG-E8 might induce efficient antitumor immune responses and enhance the potency of anti-PD-1 therapy.

Clinical application of the Lung Cancer Compact PanelTM using various types of cytological specimens in patients with lung cancer.

BACKGROUND: The Lung Cancer Compact PanelTM (compact panel) is a gene panel that can detect driver alterations with high sensitivity in liquid samples, including tumor cells. This study examined the ability of a compact panel to detect genetic mutations in liquid specimens used in clinical practice. METHODS: Three cohorts, bronchoscopic biopsy forceps washing (washing cohort), pleural effusion (pleural cohort), and spinal fluid (spinal cohort), were analyzed using the compact panel. Liquid samples were added into the GM (Genemetrics) tubes and analyzed. The washing cohort assessed the concordance rate of gene panel analysis outcomes in tissue specimens derived from the primary tumor. Meanwhile, the pleural cohort investigated the impact of storing specimens for 8 weeks and more on nucleic acid and mutation detection rates. RESULTS: In the washing cohort (n = 79), the concordance rate with mutations detected in tissues was 75/79 (94.9 %). This rate reached 100 % when focusing solely on driver alterations for treatment. The pleural cohort (n = 8) showed no deterioration in nucleic acid quality or quantity after 8 weeks of storage in GM tubes. Similarly, in the spinal cohort (n = 9), spinal fluid with malignant cells exhibited driver alterations similar to those in the primary tumor. These findings underscore the efficacy of the compact panel in accurately identifying genetic mutations in different liquid specimens. CONCLUSIONS: The compact panel is a reliable tool for detecting driver alterations in various cytological specimens. Its consistent performance across diverse sample types emphasizes its potential for guiding targeted therapies for patients with lung cancer and enhancing precision medicine approaches.

Relapsing cytokine release syndrome in a patient with metastatic renal cell carcinoma treated with pembrolizumab and axitinib therapy.

As immune checkpoint inhibitors become more widely available, the optimal management of immune-related adverse events (irAEs) is becoming increasingly important. Although irAEs are diverse, reports on cytokine release syndrome are rare. Here, we report a case of a 48-year-old man with relapsing cytokine release syndrome after receiving pembrolizumab and axitinib combination therapy for metastatic renal cell carcinoma. During dose reduction of prednisolone for immune-related hepatitis on day 33 after starting pembrolizumab plus axitinib, the patient suddenly developed abdominal pain, and a few hours later became hypotensive and poorly oxygenated. Despite the use of a ventilator and high doses of catecholamines, blood pressure and oxygenation could not be maintained. Extracorporeal membrane oxygenation and intra-aortic balloon pumping were also administered. The cytokine release syndrome (CRS) was treated with tocilizumab, and his general condition improved. Lower-grade CRS relapsed four times despite a moderate dose of oral prednisolone with mycophenolate mofetil or tacrolimus. After gradual reduction in prednisolone over 5 months, the patient was discharged from the hospital. Partial remission of renal cell carcinoma continued for 21 months, and salvage radical nephrectomy was performed. The patient remained disease-free without the need for further treatment 9 months after surgery.

Utility of needle biopsy in centrally located lung cancer for genome analysis: a retrospective cohort study.

BACKGROUND: It is essential to collect a sufficient amount of tumor tissue for successful next-generation sequencing (NGS) analysis. In this study, we investigated the clinical risk factors for avoiding re-biopsy for NGS analysis (re-genome biopsy) in cases where a sufficient amount of tumor tissue could not be collected by bronchoscopy. METHODS: We investigated the association between clinical factors and the risk of re-genome biopsy in patients who underwent transbronchial biopsy (TBB) or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and required re-genome biopsy in cases enrolled in LC-SCRUM Asia, a prospective nationwide genome screening project in Japan. We also examined whether the frequency of re-genome biopsy decreased between the first and second halves of the enrolment period. RESULTS: Of the 572 eligible patients, 236 underwent TBB, and 134 underwent EBUS-TBNA. Twenty-four TBBs required re-genome biopsy, and multivariate analysis showed that the risk of re-genome biopsy was significantly increased in lesions where the tumor lesion was centrally located. In these cases, EBUS-TBNA should be utilized even if the lesion is a pulmonary lesion. However, it should be noted that even with EBUS-TBNA, lung field lesions are at a higher risk of re-canalization than mediastinal lymph node lesions. It was also found that even when tumor cells were detected in rapid on-site evaluation, a sufficient amount of tumor tissue was not always collected. CONCLUSIONS: For centrally located pulmonary mass lesions, EBUS-TBNA, rather than TBB, can be used to obtain tumor tissues that can be analyzed by NGS.

Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8+ T cell cytotoxicity and proliferation.

Immune checkpoint inhibitors (ICIs) have caused revolutionary changes in cancer treatment, but low response rates remain a challenge. Semaphorin 4A (Sema4A) modulates the immune system through multiple mechanisms in mice, although the role of human Sema4A in the tumor microenvironment remains unclear. This study demonstrates that histologically Sema4A-positive non-small cell lung cancer (NSCLC) responded significantly better to anti-programmed cell death 1 (PD-1) antibody than Sema4A-negative NSCLC. Intriguingly, SEMA4A expression in human NSCLC was mainly derived from tumor cells and was associated with T cell activation. Sema4A promoted cytotoxicity and proliferation of tumor-specific CD8+ T cells without terminal exhaustion by enhancing mammalian target of rapamycin complex 1 and polyamine synthesis, which led to improved efficacy of PD-1 inhibitors in murine models. Improved T cell activation by recombinant Sema4A was also confirmed using isolated tumor-infiltrating T cells from patients with cancer. Thus, Sema4A might be a promising therapeutic target and biomarker for predicting and promoting ICI efficacy.

Clinical application of the AMOY 9-in-1 panel to lung cancer patients.

INTRODUCTION: To investigate the clinical performance of the AMOY 9-in-1 kit (AMOY) in comparison with a next-generation sequencing (NGS) panel in lung cancer patients. METHODS: Lung cancer patients enrolled in the LC-SCRUM-Asia program at a single institution were analyzed for the success rate of AMOY analysis, the detection rate of targetable driver mutations, the turn around time (TAT) from specimen submission to the result reporting, and the concordance rate of results with the NGS panel. RESULTS: Of the 406 patients included in the analysis, 81.3% had lung adenocarcinoma. The success rates of AMOY and NGS were 98.5% and 87.8%, respectively. With AMOY, genetic alterations were detected in 54.9% of cases. Of the 42 cases in which NGS analysis failed, targetable driver mutations were detected by AMOY in ten cases through analysis of the same sample. Of the 347 patients for whom the AMOY and NGS panels were successful, 22 showed inconsistent results. In four of the 22 cases, the mutation was detected only in the NGS panel because AMOY did not cover the EGFR mutant variant. Mutations were detected only by AMOY in five of the six discordant pleural fluid samples, with AMOY having a higher detection rate than NGS. The TAT was significantly shorter five days after AMOY. CONCLUSION: AMOY had a higher success rate, shorter turnaround time, and higher detection rate than NGS panels. Only a limited number of mutant variants were included; thus be careful not to miss promising targetable driver mutations.

Hepatitis B core-related antigen: A novel and promising surrogate biomarker to guide anti-hepatitis B virus therapy.

The current requirement for biomarkers to detect hepatitis B virus (HBV) infection is polarized. One is a fully-automated and highly sensitive measurement system; the other is a simple system for point-of-care testing (POCT) in resource-limited areas. Hepatitis B core-related antigen (HBcrAg) reflects intrahepatic covalently closed circular DNA and serum HBV DNA. Even in patients with undetectable serum HBV DNA or HBsAg loss, HBcrAg may remain detectable. Decreased HBcrAg levels are associated with reduction of the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B. Recently, a fully-automated, novel high-sensitivity HBcrAg assay (iTACT-HBcrAg, cut-off value: 2.1 logIU/mL) has been developed. This attractive assay has been released in Japan very recently. iTACT-HBcrAg can be useful for monitoring HBV reactivation and prediction of HCC occurrence, as an alternative to HBV DNA. Moreover, monitoring HBcrAg may be suitable for determining the therapeutic effectiveness of approved drugs and novel drugs under development. Presently, international guidelines recommend anti-HBV prophylaxis for pregnant women with high viral loads to prevent mother-to-child transmission of HBV. However, >95% of HBV-infected individuals live in countries where HBV DNA quantification is not available. Worldwide elimination of HBV needs the scaling-up of examination and medication services in resource-limited areas. Based on this situation, a rapid and easy HBcrAg assay as a POCT is valuable. This review provides the latest information regarding the clinical use of a new surrogate marker, HBcrAg, in HBV management, based on iTACT-HBcrAg or POCT, and introduces novel agents targeting HBV RNA/protein.

Efficacy and safety of mycophenolate mofetil in treating immune-related hepatitis induced by immune checkpoint inhibitor use: A retrospective study.

Background and Aim: To investigate the outcomes in eight Japanese patients with cancer treated with mycophenolate mofetil (MMF) and corticosteroids for immune checkpoint inhibitor treatment-induced severe immune-related hepatitis (ir-hepatitis) and the efficacy and safety of MMF. Methods: We retrospectively examined patient background, treatment course, as well as examination and imaging data using electronic medical records. Results: The ratio of male to female patients was 7:1, and the median age was 60 years (27-72 years). There were five and two cases of kidney cancer and malignant melanoma, respectively, and one case of lung cancer. The median number of days until MMF administration in addition to systemic corticosteroid therapy after the onset of ir-hepatitis was 14.5 (2-42). The patients were categorized as four "good responders" who showed an improvement in the liver function tests following MMF treatment and four "poor responders" who did not. Furthermore, the time from the onset of ir-hepatitis to initial MMF administration was significantly shorter in good responders (median 3 days, range 2-15 days) than in poor responders (median 25.5 days, range 14-42 days) (P = 0.042). No significant intergroup difference was observed in other clinical factors. No serious adverse events caused by MMF were observed in any case. Conclusions: According to these findings, early recognition of corticosteroid refractoriness and the use of MMF may be beneficial in patients with ir-hepatitis.

Bevacizumab Plus Carboplatin Plus Nab-paclitaxel for Non-squamous Non-small Cell Lung Cancer in a Real-world Setting.

BACKGROUND/AIM: Regimens with bevacizumab (Bev) have high response rates. We previously showed the efficacy of Bev plus carboplatin (CBDCA)/nab-paclitaxel (nab-PTX) in the treatment of non-squamous (non-SQ) non-small lung cell cancer (NSCLC) with malignant pleural effusion in a phase II trial. However, few studies have reported the efficacy and safety of this regimen. Therefore, we conducted a retrospective analysis of the efficacy and safety of Bev plus CBDCA/nab-PTX for patients with NSCLC. PATIENTS AND METHODS: We included patients with non-SQ NSCLC that underwent any number of treatment lines. Patients received a maximum of six cycles of Bev plus CBDCA/nab-PTX every three to four weeks followed by Bev plus nab-PTX every three to four weeks without disease progression or severe toxicities. The administration dose was left to the discretion of the attending physician. RESULTS: We enrolled 48 patients treated with Bev plus CBDCA/nab-PTX between June 2015 and August 2021. The best response rate was 56.3% and the disease control rate was 79.2%. Twenty-three patients received maintenance therapy. Median progression-free and overall survival times were 6.8 and 10.4 months, respectively. Common adverse events included hematological toxicities, including ≥grade 3 neutropenia and neurosensory toxicity. One patient experienced severe bleeding events (grade 3 gastrointestinal bleeding) and another experienced grade 5 toxicity (infection). CONCLUSION: The combination of Bev plus CBDCA/nab-PTX showed good efficacy with acceptable toxicities in non-SQ NSCLC patients, despite the inclusion of patients with late treatment lines and poor performance status.

Rapid Response to Sotorasib of a Patient With KRAS G12C-Mutated Lung Cancer With Cancer-Associated Disseminated Intravascular Coagulation: A Case Report.

The efficacy of sotorasib for patients with KRAS G12C-mutated lung cancer with poor performance status (PS) and active brain metastases remains unknown. Here, we present a case in which sotorasib was introduced as the third-line therapy for a patient whose PS worsened due to active multiple brain metastases and disseminated intravascular coagulation (DIC) caused by rapid tumor progression; a marked effect was observed. DIC and PS improved two weeks after the start of the administration, and multiple brain metastases disappeared. The effect lasted only approximately four months due to the development of a new liver metastasis, but sotorasib improved PS and the DIC status was reversed, allowing for further treatment. Sotorasib could be considered for introduction in patients with poor PS.

A longitudinal study to detect hepatitis B surface and core-related antigens in chronic hepatitis B patients with hepatitis B surface antigen seroclearance using highly sensitive assays.

BACKGROUND: This study aimed to evaluate the usefulness of two novel assays, namely the iTACT-hepatitis B surface antigen (iTACT-HBsAg) and iTACT-hepatitis B core-related antigen (iTACT-HBcrAg) assays, in chronic hepatitis B (CHB) patients with HBsAg seroclearance (SC) documented by standard assays. METHODS: HBsAg and HBcrAg were measured by the two iTACT-assays in 556 serial sera collected from 96 CHB patients at 7 different time points spanning from 5 years before to 10 years after SC and 120 HBsAg-negative, anti-HBc-positive individuals. As controls, 60 seronegative individuals, who were negative for HBsAg, anti-HBc and anti-HBs, were tested. RESULTS: Using the iTACT-assays, HBsAg was detectable in 154/418 (36.8%) samples collected after SC. HBcrAg was detectable in 78.3% and 65.9% of samples collected before and after SC, respectively. The detectability rates of both HBsAg and HBcrAg progressively decreased over time after SC. At 10 years after SC, 20.4% and 64.5% of the patients still had detectable HBsAg and HBcrAg, respectively. 66 (71%) patients had detectable HBsAg and/or HBcrAg. Among the 120 HBsAg-negative, anti-HBc-positive individuals, 11 (9.2%) and 4 (3.3%) had detectable HBsAg and HBcrAg respectively. Both HBsAg and HBcrAg were undetectable in the controls. CONCLUSION: The iTACT assays detected a low level of HBsAg and/or HBcrAg in >70% of patients even at 10 years after SC, suggesting that CHB patients with SC still harbour a low level of HBV protein expression. The clinical significance of detectable viral proteins after SC with regard to disease progression and HBV reactivation deserves further investigations.

Rapid and reliable collection of tumor tissue for successful gene panel in a patient with advanced stage lung cancer: A case report.

Rapid and reliable identification of targetable driver mutations in patients with advanced stage lung cancer is essential. Adequate amount of tumor tissue biopsies (i.e., genomic biopsies) are required to successfully analyze the gene panel. In the present case, we performed three pleural fluid investigations, including transbronchial biopsy of the primary tumor, transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of lymph node metastasis, and thoracoscopic biopsy of the pleural seeding sites. Among the three investigations, thoracoscopic biopsy alone successfully obtained a sufficient amount of tissue. Thus, it is important to determine the technique and site of biopsy, as multiple biopsies are not only burdensome to the patient, but also lead to significant delays in therapy induction.

Outcome of nucleos(t)ide analog cessation in patients with treatment for prevention of or against hepatitis B virus reactivation.

AIM: We retrospectively investigated patients with administration of nucleos(t)ide analogs (NAs) for prevention of or against hepatitis B virus (HBV) reactivation, and their clinical outcomes after cessation of the NA. METHODS: We enrolled 180 patients who were positive for HBsAg when they started immunosuppressive therapy or chemotherapy and an NA was administered to prevent HBV reactivation (HBV carrier group), and 82 patients with resolved HBV infection who started administration of an NA after HBV reactivation (de novo HBV group). Cessation of the NA depended on each physician's judgment without definite criteria. RESULTS: A total of 27 patients in the HBV carrier group and 22 in the de novo HBV group stopped NA therapy. In the HBV carrier group, 16 patients experienced virological relapse, which was defined as HBV DNA levels ≥20 IU/ml, and one with hematological disease had an alanine aminotransferase flare after cessation of NA. Of the 16 patients, the NA was reintroduced in three, whereas, the remaining 13 had low levels of HBV DNA and no alanine aminotransferase flare. In the de novo HBV group, virological relapse occurred in six patients, and one with hematological disease had an alanine aminotransferase flare after cessation of the NA. The NA was reintroduced in four of the six patients. CONCLUSIONS: We may be able to consider to cease NA therapy proactively in HBV carriers and resolved patients with non-hematological disease, if their primary diseases are under remission after completion of immunosuppressive therapy or chemotherapy. However, careful follow up is necessary after stopping NA therapy.

Prevalence and characteristics of immune checkpoint inhibitor-related myocardial damage: A prospective observational study.

An increasing number of patients with cancer are being treated with immune checkpoint inhibitors. Consequently, the incidence of immune checkpoint inhibitor-related myocarditis has been increasing. Nonetheless, the diagnostic criteria for the immune checkpoint inhibitor-related myocarditis have not been sufficiently established. Therefore, the real-world incidence or prevalence of immune checkpoint inhibitor-related myocardial damage remains unknown. This was a single-center cohort study that included 100 patients admitted for immune checkpoint inhibitor therapy for any type of cancer. The patients underwent monthly measurement of cardiac troponin I and N-terminal pro-brain natriuretic peptide levels with electrocardiography. Additionally, echocardiography was performed every 3 months. Our protocol was continued until 6 months after the initiation of immune checkpoint inhibitors. We defined immune checkpoint inhibitor-related myocardial damage as an increase in cardiac troponin I levels by >0.026 ng/mL and/or a decrease in the left ventricular ejection fraction by >10% to <53% on echocardiography. The mean patient age was 64 years; 71% were men. The most commonly used immune checkpoint inhibitor was nivolumab (47%), followed by pembrolizumab (29%). Overall, 5% of patients received combination therapy. Among 100 patients, 10 (10%) were diagnosed with immune checkpoint inhibitor-related myocardial damage. Among them, five patients underwent endomyocardial biopsy. Of these patients, four were histopathologically observed to have lymphocyte infiltration in their myocardium. In conclusion, serial cardiac troponin I measurement during immune checkpoint inhibitor treatment could help detect early-phase myocardial damage. The prevalence of myocardial damage was much higher than previously expected.

Clinical application of comprehensive genomic profiling panel to thoracic malignancies: A single-center retrospective study.

BACKGROUND: The usefulness of comprehensive genomic profiling (CGP) panels for thoracic malignancies after completion of the standard treatment is unclear. METHODS: The results of CGP panels for malignant thoracic diseases performed at our hospital between December 2019 and June 2022 were collected. We examined whether CGP panel results led to new treatment, correlated with the effectiveness of immune checkpoint inhibitors (ICIs), or revealed secondary findings related to hereditary tumors. RESULTS: A total of 60 patients were enrolled, of which 52 (86.6%) had lung cancer. In six (10%) patients, the panel results led to treatment with insurance-listed molecular-targeted agents; four patients had EGFR mutations not detected by the real-time polymerase chain reaction assay and two had MET ex.14 skipping mutations. In small-cell lung cancer, the tumor mutation burden was high in 4/6 (66.7%) patients and pembrolizumab was available. Another MET ex.14 skipping mutation was detected in two cases with EGFR-tyrosine kinase inhibitor resistance. ICI efficacy was ≤1 year in patients with STK-11, KEAP1, and NEF2L2 mutations. A BRCA2 mutation with a high probability of germline mutation was detected in one patient. A thymic carcinoma with no detectable oncogenic mutation responded to second-line treatment with Tegafur-Gimeracil-Oteracil Potassium (TS-1) for ≥9 years. CONCLUSIONS: CGP panels are useful in thoracic malignancies, especially lung cancer, because they can detect overlooked driver mutations and genetic alterations. We believe that the significance of conducting a CGP panel prior to treatment may also exist, as it may lead to the prediction of ICI treatment efficacy.

Immunochemotherapy Disrupts Peripherally Located Lung Squamous Cell Carcinoma Resulting in Pleuritis: A Report of Two Cases, Case Report.

Immunochemotherapy is widely used as the primary treatment for advanced lung cancer and is currently being investigated in the perioperative setting. Immunochemotherapy can produce marked tumor shrinkage and long-term anticancer effects that are not achieved with conventional anticancer drugs. Herein, we present the cases of two patients with relatively large advanced primary lung squamous cell carcinomas located just below the pleura, who developed pleuritis immediately after the initiation of immunochemotherapy, probably owing to leakage of tumor contents after marked tumor shrinkage. Treatment of pleuritis necessitates discontinuation of chemotherapy, and special attention to secondary pleuritis may be required after initiation of immunochemotherapy in patients with lung tumors located just below the pleura.

A Case of Lung Cancer with Very-Late-Onset Immune Checkpoint Inhibitor-Related Myocarditis.

Immune checkpoint inhibitor (ICI)-related myocarditis has been reported to appear in the early phase after ICI initiation. Herein, we report the case of a 78-year-old man with non-small cell lung cancer. Pembrolizumab was introduced as first-line therapy. After 9 months, second-line therapy, including bevacizumab, was initiated. After another 7 months, echocardiography showed diffuse left ventricular dysfunction. Based on the histopathologic examination of the myocardium, the patient was diagnosed with ICI-related myocarditis. Initiation of prednisolone therapy improved cardiac function. This case of late-onset ICI-related myocarditis illustrates that endomyocardial biopsy can be useful in the differential diagnosis of cancer-related left ventricular dysfunction.

Il a été rapporté qu'une myocardite pouvait survenir peu après l'instauration d'un traitement par des inhibiteurs des points de contrôle immunitaire (ICI). Nous présentons le cas d'un homme de 78 ans atteint d'un cancer du poumon non à petites cellules. Le pembrolizumab a été administré comme traitement de première intention. Neuf mois plus tard, un traitement de deuxième intention par le bévacizumab a été instauré. Après sept autres mois, l'échocardiographie a montré une dysfonction ventriculaire gauche diffuse. À la suite des résultats de l'examen histopathologique du myocarde, une myocardite liée aux ICI a été diagnostiquée. L'instauration d'un traitement par la prednisolone a amélioré la fonction cardiaque du patient. Ce cas de myocardite tardive liée aux ICI montre l'utilité éventuelle de la biopsie de l'endomyocarde dans le diagnostic différentiel d'une dysfonction ventriculaire gauche liée au cancer.