Biomarkers for Immune Checkpoint Inhibitors in Mesothelioma: What Are the Roles of Biomarkers for Optimal Immune Therapy?

2021 ◽  
pp. 267-278
Author(s):  
Toshiyuki Minami ◽  
Takashi Kijima
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Therapy

Analysis of metastatic melanoma treated with immune checkpoint inhibitors and the rates of adverse events of colitis and hepatitis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21591-e21591
Author(s):  
Emily Horan ◽  
Melissa Arneil ◽  
Wen Xu ◽  
Victoria Atkinson
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Complete Response ◽  
Treatment Regimens ◽  
Organ Systems ◽  
Oral Steroids ◽  
Intravenous Steroids

e21591 Background: Immune checkpoint inhibitors (CPI) are widely used in metastatic melanoma (MM), where it has markedly improved survival outcomes. ICI induced autoimmune adverse reactions (irAE) manifest in all organ systems and are due to over-activation of the immune system. Clinically relevant irAE are colitis and hepatitis as drivers of morbidity and mortality. Methods: Data was collected from a single centre (Princess Alexandra Hospital) from the electronic medical records system and immunotherapy prescribing software. Patient demographics, treatments, complications and outcomes were recorded from 2016-2019. Eligible patients had to have received immunotherapy (pembrolizumab, ipilimumab, or nivolumab) and experienced colitis or hepatitis toxicity. Trial patients were excluded. Results: The cohort of 337 patients who had received immune therapy, 18% (n = 61) had hepatitis or colitis, mean age was 56 years, 64% male. The majority were stage 4d 28% (n = 17). Braf wildtype accounted for 56% (n = 34). The highest rates of irAE occurred on combination ipilimumab and nivolumab 56% (n = 34), 10% nivolumab (n = 6), 3% (n = 2) ipilimumab, and 31% (n = 19) pembrolizumab monotherapy. Colitis affected 61% of patients (n = 37), 30% (n = 18) were grade 3 severity. Hepatitis affected 48% (n = 29), 18% (n = 32) were grade 1. The majority required oral steroids (80%, n = 49), followed by intravenous steroids (51%, n = 31), infliximab (18%, n = 11) and mycophenolate in 5% (n = 3). Hospitalisation occurred in 56% (n = 34), 20% (n = 12) requiring treatment cessation. Progressive disease occurred in 62% (n = 38), and 13% (n = 8) had a complete response. Conclusions: The findings of this analysis mirror current literature with immunotherapies used, rates and severity of irAE. The management of irAE also aligned with current guidelines. Further research is required to investigate patient factors increasing the risk of developing irAE, and ideal treatment regimens. Analysing this large cohort, the incidence of toxicity was 17%, predominantly colitis followed by hepatitis. Patients were severely impacted requiring significant interventions to manage toxicity, hospitalisation and morbidity.

Tamponade during immune checkpoint inhibitors therapy in lung cancer: case-reports and systematic review of the literature

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Mustafic ◽  
A Celebic ◽  
S Lannou ◽  
S Mallet ◽  
A Vieillard Baron ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Smoking Cessation ◽  
Cancer Therapy ◽  
Mortality Rate ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Immune Therapy ◽  
Pericardial Fluid

Abstract Introduction Immune therapy is a new option that has revolutionized cancer therapy. Immune checkpoint inhibitors target mostly either PD-1 (Pembrolizumab, Nivolumab) or PD-L1 (Durvalumab). Immune-related cardiotoxic side effects, among them, tamponade, initially thought to be rare, seem to be increasingly cited in the literature. Moreover, tobacco smoking is linked to 80% of lung cancers. Smoking during cancer therapy may influence on radiotherapy and chemotherapy outcomes but little is known on immunotherapy. Purpose We aimed to review all the published cases of tamponade during immune therapy for lung cancer and to report all the cases that occurred in the University Hospital Ambroise Paré. We also wanted to highlight the possible impact of tobacco on immunotherapy. Methods We conducted a literature review in the PubMED database, from database inception up to 02/14/2020, with a combination of the following terms: “tamponade AND ((immune checkpoint inhibitors) OR (PD-1) OR (PD-L1))”. We also reported all the tamponade cases occurred in our hospital from the beginning of immune checkpoint inhibitors therapy existence up to 02/14/2020. Results Seventeen cases citing tamponade were identified in the literature to which we added 3 cases from our hospital. Mortality rate at 1 month was of 20%. Nivolumab was involved in 80%, Pembrolizumab in 10% and Durvalumab in 10%. In 75%, lung cancer was with a stage IV. Men accounted for 85% and mean age was of 62 years. Active smokers represented 85% and passive smokers existed in 5%, after diagnosis, smoking cessation was done in 10%. Tamponade occurred either shortly after the first administrations but also after several doses. Pericardial fluid cytology revealed malignant cells in half of the cases and microbiology was always negative. For all the cases, excepted for one who was directly considered as palliative, an evacuation of the pericardial fluid was done. In 45% a corticotherapy was initiated. Two cases quickly worsened after pericardial evacuation by unmasking a probable myocarditis with cardiogenic shock which needed the use of a veno-arterial extracorporeal membrane oxygenation. Conclusions Tamponade under immune checkpoint inhibitors therapy appears less rare than initially thought and mortality rate at one month was not negligible. The use of regular echocardiography during this immune therapy may be crucial in detecting early stages of the disease process and smoking cessation should also be advised for these patients. The prevalence of complications among all the patients both exposed to immune therapy and tobacco could not be calculated in this work (case-reports), but some recent studies may indicate survival gains of smoking cessation. Further research establishing more specific guidelines is naturally necessary in dealing with this potentially fatal effect but also in establishing the possibly additional role of smoking in the cardiotoxicity of immunotherapy. Funding Acknowledgement Type of funding source: None

scholarly journals Immune Checkpoint Inhibitors in the Treatment of HCC

2021 ◽  
Vol 10 ◽  
Author(s):  
Clelia Donisi ◽  
Marco Puzzoni ◽  
Pina Ziranu ◽  
Eleonora Lai ◽  
Stefano Mariani ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Standard Of Care ◽  
Adoptive Cell Transfer ◽  
Phase Iii ◽  
Combination Strategy ◽  
Line Setting

Hepatocellular carcinoma (HCC) is the typical inflammation-induced neoplasia. It often prospers where a chronic liver disease persists, thus leading a strong rationale for immune therapy. Several immune-based treatments, including immune checkpoint inhibitors (ICI), cytokines, adoptive cell transfer, and vaccines, have been tested in the treatment of HCC. In this review, we summarize the role of the ICI in HCC patients in various sets of treatment. As for advanced HCC, the anti-Programmed cell Death protein 1 (PD1) antibodies and the anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibodies have been examined in patients with enthusiastic results in phase I-II-III studies. Overall, this led the Food and Drug Administration (FDA) to approve pembrolizumab, nivolumab, and nivolumab + ipilimumab in the second-line setting. The anti- Programmed Death-Ligand 1 (PDL-1) antibodies have also been evaluated. Thanks to the results obtained from phase III IMbrave study, atezolizumab + bevacizumab is now the standard of care in the first-line advanced setting of HCC. As for localized HCC, the putative immunological effect of locoregional therapies led to evaluate the combination strategy with ICI. This way, chemoembolization, ablation with radiofrequency, and radioembolization combined with ICI are currently under study. Likewise, the study of adjuvant immunotherapy following surgical resection is underway. In addition, the different ICI has been studied in combination with other ICI as well as with multikinase inhibitors and anti-angiogenesis monoclonal antibody. The evidence available suggests that combining systemic therapies and locoregional treatments with ICI may represent an effective strategy in this context.

scholarly journals Vitiligo-like Leukoderma as an Indicator of Clinical Response to Immune Checkpoint Inhibitors in Late-stage Melanoma Patients

2021 ◽  
Author(s):  
Sofia Verkhovskaia ◽  
Francesca Romana Di Pietro ◽  
Simona Mastroeni ◽  
Maria Luigia Carbone ◽  
Damiano Abeni ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cox Model ◽  
Immune Therapy ◽  
Group Analysis ◽  
Favorable Outcome ◽  
Clinical Benefits ◽  
Melanoma Patients

Abstract Purpose. Although development of immune checkpoint inhibitors has revolutionized the treatment of metastatic melanoma, more than a half of treated patients experience disease progression during therapy. Cases of spontaneous vitiligo-like leukoderma have been described in melanoma patients and have been associated with a favorable outcome. This vitiligo-like leukoderma can also appear in melanoma patients undergoing immune therapies such as immune checkpoint inhibitors. However, no consensus exists about the relationship between vitiligo-like leukoderma onset and improved overall survival. Our study investigates the possible association between the onset of vitiligo-like leukoderma during immune checkpoint inhibitor treatment and a better prognosis.Methods. A non-concurrent cohort study was conducted by identifying retrospectively 280 patients who had inoperable or metastatic melanoma and had undergone immune therapy with checkpoint inhibitors in any line of treatment. Toxicities developed during therapy were evaluated. Results. Among the 280 study participants, 50% developed at least one type of toxicity, and vitiligo-like leukoderma was observed in 43 patients (15.4%). In the multivariate Cox model, a protective effect for mortality was observed for patients with vitiligo-like leukoderma development (HR = 0.23; 95% CI = 0.11-0.44, p <0.0001). In a sub-group analysis comprising only cutaneous melanoma in first line of treatment (N=153), occurrence of vitiligo-like leukoderma was also an independent predictor factor for duration of clinical benefits measured by time to the next treatment (HR:0.17; 95% CI:0.06-0.44). Conclusion. Our findings indicate that onset of vitiligo-like leukoderma during melanoma treatment could be a marker of favorable outcome in patients treated with immune checkpoint inhibitors.

scholarly journals Longitudinally Extensive Myelitis Associated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 8 (3) ◽  
pp. e967
Author(s):  
Alberto Picca ◽  
Giulia Berzero ◽  
Kevin Bihan ◽  
Vincent Jachiet ◽  
Edouard Januel ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
High Dose ◽  
Peripheral Nerve Involvement ◽  
Sensory Disturbances ◽  
Immune Therapies ◽  
Improve Patient

ObjectiveTo define the characteristics and the outcome of myelitis associated with immune checkpoint inhibitors (ICIs).MethodsWe performed a retrospective research in the databases of the French Pharmacovigilance Agency and the OncoNeuroTox network for patients who developed myelitis following treatment with ICIs (2011–2020). A systematic review of the literature was performed to identify similar cases.ResultsWe identified 7 patients who developed myelitis after treatment with ICIs (anti-PD1 [n = 6], anti-PD1 + anti-CTLA4 [n = 1]). Neurologic symptoms included paraparesis (100%), sphincter dysfunction (86%), tactile/thermic sensory disturbances (71%), and proprioceptive ataxia (43%). At the peak of symptom severity, all patients were nonambulatory. MRI typically showed longitudinally extensive lesions, with patchy contrast enhancement. CSF invariably showed inflammatory findings. Five patients (71%) had clinical and/or paraclinical evidence of concomitant cerebral, meningeal, caudal roots, and/or peripheral nerve involvement. Despite the prompt discontinuation of ICIs and administration of high-dose glucocorticoids (n = 7), most patients needed second-line immune therapies (n = 5) because of poor recovery or early relapses. At last follow-up, only 3 patients had regained an ambulatory status (43%). Literature review identified 13 previously reported cases, showing similar clinical and paraclinical features. All patients discontinued ICIs and received high-dose glucocorticoids, with the addition of other immune therapies in 8. Clinical improvement was reported for 10 patients.ConclusionMyelitis is a rare but severe complication of ICIs that shows limited response to glucocorticoids. Considering the poor functional outcome associated with longitudinally extensive myelitis, strong and protracted immune therapy combinations are probably needed upfront to improve patient outcome and prevent early relapses.

Response of metastatic mucosal melanoma to immunotherapy: It can get worse before it gets better

2016 ◽  
Vol 23 (3) ◽  
pp. 215-219 ◽  
Author(s):  
Shebli Atrash ◽  
Issam Makhoul ◽  
Jason S Mizell ◽  
Laura Hutchins ◽  
Fade Mahmoud
Keyword(s):  
Computed Tomography ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Mucosal Melanoma ◽  
Response To Treatment ◽  
Computed Tomography Scans ◽  
New Onset

Immune therapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. Ipilimumab, nivolumab, and pembrolizumab are all FDA-approved immune checkpoint inhibitors to treat metastatic melanoma. Responses to immune checkpoint inhibitors are usually delayed. An interim progression on restaging computed tomography scans “pseudo-progression” may be observed before response to treatment occur. In this case, we report a significant interim progression of metastatic mucosal melanoma before meaningful responses to immunotherapy occurred. The patient developed significant immune therapy-related colitis and new onset vitiligo. Further restaging computed tomography scans showed sustained tumor response despite stopping the immune therapy.

scholarly journals PROSPECTS OF COMBINING INTERLEUKIN-2 WITH IMMUNE CHECKPOINT INHIBITORS FOR CANCER THERAPY

2020 ◽  
Vol 66 (1) ◽  
pp. 23-28
Author(s):  
Mikhail Kiselevskiy ◽  
Irina Chikileva ◽  
O. Zharkova ◽  
N. Ziganshina ◽  
Lyubov Korolenkova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Interleukin 2 ◽  
Combination Therapies ◽  
Activated Lymphocytes ◽  
Therapy Strategy ◽  
Clinical Investigations

The review summarizes results of pre-clinical and clinical investigations of combination therapies with interleukin-2 and immune checkpoint inhibitors. It presents data of the current registered clinical trials of immune checkpoint combinations either with interleukin-2 or the cytokine-activated lymphocytes. The up-to-date experimental and preliminary clinical data evidence that such an immune therapy strategy is highly promising for cancer treatment.

Abstract #827: Panhypopituitarism Due to Immune Checkpoint Inhibitors

2017 ◽  
Vol 23 ◽  
pp. 176-177
Author(s):  
Kaitlyn Steffensmeier ◽  
Bahar Cheema ◽  
Ankur Gupta
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors
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