scholarly journals Cutaneous Events Associated with Immunotherapy of Melanoma: A Review

2021 ◽  
Vol 10 (14) ◽  
pp. 3047
Author(s):  
Lorenza Burzi ◽  
Aurora Maria Alessandrini ◽  
Pietro Quaglino ◽  
Bianca Maria Piraccini ◽  
Emi Dika ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Stage Iii ◽  
Check Point ◽  
Check Point Inhibitors

Immunotherapy with checkpoint inhibitors significantly improves the outcome for stage III and IV melanoma. Cutaneous adverse events during treatment are often reported. We herein aim to review the principal pigmentation changes induced by immune check-point inhibitors: the appearance of vitiligo, the Sutton phenomenon, melanosis and hair and nail toxicities.

Clinical outcomes of patients on check point inhibitor therapy who receive routine vaccinations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14597-e14597 ◽  
Author(s):  
Erin Lynn Schenk
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Median Survival ◽  
Routine Vaccination ◽  
Check Point ◽  
Similar Frequency ◽  
Advanced Malignancies ◽  
Check Point Inhibitors ◽  
Single Vaccination ◽  
Grade 3

e14597 Background: Routine vaccination reduces preventable illness and infection in cancer patients even while undergoing therapy. Increasingly, patients with advanced malignancies receive check point inhibitors (CPI) and, with tumor response, can remain on therapy for extended periods of time. These agents promote tumor clearance by impeding a normal route of immune regulation which can result in autoimmunity. To the best of our knowledge, clinical outcomes for patients on CPI therapy who receive routine vaccinations have not been studied. Methods: The medical records of patients who received CPI therapy at Mayo Clinic in Rochester, Minnesota from March 25, 2011 to August 25, 2015 were reviewed for type and date of immunizations, CPI duration, adverse events (AE) at least possibly related to therapy, and survival from start of CPI. Patients who received > 1 dose of pembrolizumab or nivolumab were included in analysis. Patients were excluded if no follow up was done at our institution. Results: One hundred and eight patients were included in the analysis. Most patients received CPI therapy for metastatic melanoma (n = 71) or non-small cell lung cancer (n = 23). A total of 53 routine vaccinations were administered to 30 patients while on CPI therapy. Eighteen patients received a single vaccination. Annual influenza vaccination was most frequently administered (n = 38) followed by pneumococcal vaccines (n = 9). AEs were reported in 17/30 vaccinated patients and in 22/78 non-vaccinated patients (p = 0.004). In the vaccinated cohort, 11 patients experienced AEs after immunization and was not significantly different from the non-vaccinated patients (p = 0.265). For both cohorts, thyroid, rash, and pneumonitis were the most common AEs. Grade 3 AEs occurred with similar frequency between the 2 groups. Patients in the vaccinated cohort received more cycles of therapy (median 20.5 vs 6 cycles, p < 0.001). Median survival of patients who were not vaccinated was 503 days and median survival was not reached in the vaccinated group (p = 0.005). Conclusions: Routine vaccination of patients receiving CPI therapy did not significantly increase number or severity of adverse events. Routine vaccination did not reduce patient benefit from CPIs.

scholarly journals SAT-239 Combination of Immune Check Point Inhibitors Causing Hypopituitarism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Puneet Dhillon ◽  
Harshwant Grover ◽  
Jonathan Slusser ◽  
Neethu Gopisetti ◽  
Tirth Patel
Keyword(s):  
Pituitary Gland ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Stable Condition ◽  
Surgical Excision ◽  
Check Point ◽  
Free T4 ◽  
Secondary Hypothyroidism ◽  
Check Point Inhibitors ◽  
Vulvar Melanoma

Abstract Introduction: Immune Check Point inhibitors (ICI) have been associated with immune related adverse events including a wide array of Endocrinopathies particularly when a combination of ICIs is used. We present a case of Hypopituitarism secondary to CTLA-4 inhibitor Iplimumab and PD-1 inhibitor Pembrulizumab in a patient with Vulvar Melanoma. Case Description: 49-year-old female with past medical history of Type 2 Diabetes and Vulvar Melanoma presented with nausea, vomiting and fatigue. The patient had surgical excision of Vulvular Melanoma and had been on chemotherapy with Pembrolizumab and Ipilimumab for 1 month. She was found to be hypotensive in the ER, but blood pressure improved after fluid resuscitation. Her blood sugar levels were 76 MG/DL. She denied using any insulin in the last 24 hours. AM Cortisol was &lt;1 UG/ML. TSH was 0.205 UIU/ML with free T4 at 0.74 NG/DL. FSH was 2.5 MIU/ML. LH was 0.5 MIU/ML. Prolactin was 90.2 NG/ML. ACTH was less than 9 PG/ML. MRI of the brain showed mildly enlarged pituitary gland with suprasellar extension, measuring 10.5 mm in craniocaudal height and normal homogeneous enhancement. A diagnosis of Hypopituitarism secondary Ipilimumab and Pembrolizumab was made. She was started on steroids and thyroid replacement. The patient’s symptoms resolved, and she was discharged home in a stable condition with outpatient Endocrinology follow up. Discussion: Immune checkpoint inhibitors (ICI) includes PD1(Programmed cell death receptor 1) inhibitors like Pembrolizumab and CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) inhibitors like Ipilimumab. CTLA-4 inhibitors have more frequently been associated with Hypophysitis leading to particularly ACTH and TSH deficiencies and causing secondary adrenal insufficiency and secondary hypothyroidism. Posterior Pituitary involvement is less common. MRI usually shows mild to moderate enlargement of the pituitary gland. ICI therapy usually does not need to be stopped. Patients commonly require long term glucocorticoid and thyroid replacement.

scholarly journals Immune Checkpoint Myocarditis from Adjuvant Treatment of Melanoma

2020 ◽  
pp. 1-2
Author(s):  
Carrie Lenneman ◽  
John Dasher ◽  
Lavanya Kondapalli ◽  
Carrie Lenneman
Keyword(s):  
T Cells ◽  
High Risk ◽  
Adverse Events ◽  
Adjuvant Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Effective Therapy ◽  
Stage Iii

Immune checkpoint inhibitors (ICIs) are effective therapy for many metastatic cancers and are now being used as adjuvant treatment for many stage III cancers to reduce the high risk of reoccurrence. ICIs activate a patient’s own T-cells to fight cancer, but in some cases, immune-related adverse events (irAEs) with inflammation of many organs can occur. Rare cases of myocarditis have been reported. More data is needed to improve our ability to monitor, diagnose and treat irAEs.

scholarly journals Immunotherapy in Patients with Lung Cancer with Driver Mutations: A Single-Centre Experience

2021 ◽  
Author(s):  
Amit Rauthan ◽  
Poonam Patil ◽  
Rajashree Aswath ◽  
Nitin Yashas ◽  
Gaurav Ningade
Keyword(s):  
Tumor Tissue ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Single Gene ◽  
Driver Mutation ◽  
Driver Mutations ◽  
Check Point ◽  
Ras Mutation ◽  
Gene Testing ◽  
Check Point Inhibitors

Abstract Introduction Immunotherapy has revolutionized treatment in metastatic nonsmall cell lung cancer (NSCLC) without driver mutations. Trial data shows that programmed death-1/PDL1 blockade in epidermal growth factor receptor (EGFR) and other driver mutation positive lung cancers is not beneficial; and instead maybe detrimental. Here, we evaluated the efficacy of immune check point inhibitors in a series of patients with EGFR and other driver mutation–positive advanced NSCLC. Objectives This study was aimed to evaluate the efficacy of immune check point inhibitors in a series of patients with EGFR and other driver mutation–positive advanced NSCLC. Materials and Methods We retrospectively analyzed 75 patients which received PD1/PDL1 inhibitors for advanced NSCL between January 2017 and January 2020. Ten patients were detected to have driver mutations on either tumor tissue or blood by next-generation sequencing (NGS). PDL1 status was assessed on SP263 ventana platform. Results Out of 10 patients, 7 were male and 3 were female. EGFR was detected in six patients (three on tumor and three in blood NGS), MET exon 14 skipping mutation in two patients, and RAS mutation in two patients on NGS in blood. Immunotherapy combined with chemotherapy was given in 5 (50%) patients, immunotherapy + bevacizumab + chemotherapy in two (20%) and immunotherapy alone in three patients (30%). Immunotherapy was started as first line in four patients as tumor tissue was negative for EGFR, ALK, and ROS1 by single gene testing. The remaining six patients received immunotherapy on progression in the second or subsequent lines. On NGS testing at progression, EGFR mutation was detected in one patient, MET exon 14 skip mutation was detected in two patients, and RAS mutation was detected in two patients. Immunotherapy alone was used in three patients in view of advanced age and multiple comorbidities. The median progression-free survival (PFS) was 5 months (range: 2–11 months). Two patients who received chemotherapy + bevacizumab + immunotherapy continue to do well without progression at 9 months. Conclusion PD1/PDL1 checkpoint inhibitors seem to have a limited impact in treatment in patients with driver mutations. Molecular testing by NGS is recommended either on tumor tissue or on blood by NGS if single gene testing for EGFR/ALK/ROS1 alterations is negative. We recommend not using single agent checkpoint inhibitors in molecular driven advanced NSCLC even with high PDL1 expression. We do see benefit in patients who received PD1/PDL1 inhibitors in combination with chemotherapy with bevacizumab. In conclusion, in patients with molecular-driven NSCLC who progress after standard therapy can be treated with PD1/PDL1 inhibitors, but this should always be given in combination with chemotherapy and bevacizumab.

scholarly journals Cancer Immunotherapy Dosing: A Pharmacokinetic/Pharmacodynamic Perspective

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 632
Author(s):  
Félicien Le Louedec ◽  
Fanny Leenhardt ◽  
Clémence Marin ◽  
Étienne Chatelut ◽  
Alexandre Evrard ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Random Effect ◽  
Clinical Development ◽  
Dose Finding ◽  
Therapeutic Drug ◽  
Check Point ◽  
Economic Aspects ◽  
Check Point Inhibitors ◽  
Antitumoral Action

Immune check-point inhibitors are drugs that are markedly different from other anticancer drugs because of their indirect mechanisms of antitumoral action and their apparently random effect in terms of efficacy and toxicity. This marked pharmacodynamics variability in patients calls for reconsidering to what extent approved dosing used in clinical practice are optimal or whether they should require efforts for customization in outlier patients. To better understand whether or not dosing could be an actionable item in oncology, in this review, preclinical and clinical development of immune checkpoint inhibitors are described, particularly from the angle of dose finding studies. Other issues in connection with dosing issues are developed, such as the flat dosing alternative, the putative role therapeutic drug monitoring could play, the rise of combinatorial strategies, and pharmaco-economic aspects.

Review of neurological side effects associated with checkpoint inhibitor therapy in cancer patients.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 72-72
Author(s):  
Lakshmi Manogna Chintalacheruvu ◽  
Kushal Naha ◽  
Vamsi Krishna Chilluru ◽  
Donald C. Doll
Keyword(s):  
Side Effects ◽  
Confidence Interval ◽  
Randomized Controlled Trials ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Controlled Trials ◽  
Close Monitoring ◽  
Check Point ◽  
Randomized Controlled ◽  
Check Point Inhibitors

72 Background: Checkpoint inhibitors have demonstrated efficacy in many cancer types. Neurological side effects are not well studied with check point inhibitors therapy. We conducted systematic review and meta analysis to evaluate the incidence of neurological side effects among various check point inhibitors. Methods: Eligible studies were searched for in PubMed and Google scholar. We searched for randomized controlled trials with cancer patients treated with check point inhibitors with neurological adverse effects. A total of 26 randomized controlled trials involving 6110 patients met eligibility criteria for the study. Results: Incidence rate of all grade neurological side effects include 5.6%(95% confidence interval [CI], 5.4-6.7%). Most common side effects include Headache (4.6%) (95% confidence interval [CI] 3.7-4.7%) followed by peripheral neuropathy (0.3%) (95% confidence interval [CI] 0.1-0.5%). Ipilimumab plus Nivolumab is associated with higher risk of headache and serious neurological side effects including myasthenia gravis, encephalitis, toxic encephalopathy and seizures. Conclusions: The incidence of neurological side effects associated with immune checkpoint inhibitors is low but not negligable. Patients on combination immunotherapy need more close monitoring for serious neurological side effects.

scholarly journals Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Wanting Hou ◽  
Xiaohan Zhou ◽  
Cheng Yi ◽  
Hong Zhu
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Check Point ◽  
Small Cell Lung ◽  
Immune Microenvironment ◽  
Malignant Solid Tumor ◽  
Check Point Inhibitors

Small cell lung cancer (SCLC) is a malignant solid tumor. In recent years, although immune check point inhibitors (ICIs) have achieved important advances in the treatment of SCLC, immune-related adverse events (irAEs) have occurred at the same time during the therapeutic period. Some irAEs lead to dose reduction or treatment rejection. The immune microenvironment of SCLC is complicated, therefore, understanding irAEs associated with ICIs is of great importance and necessity for the clinical management of SCLC. However, the lack of comprehensive understanding of irAEs in patients with SCLC remains remarkable. This review aims to provide an up-to-date overview of ICIs and their associated irAEs in patients with SCLC based on present clinical data.

Immuno-related adverse events from check-point inhibitors during immune-therapy for cancer. Imaging findings

2018 ◽  
Vol 92 ◽  
pp. S22
Author(s):  
F. Sandomenico ◽  
G. De rosa ◽  
S. Pizza ◽  
O. Catalano ◽  
S. Setola ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cancer Imaging ◽  
Immune Therapy ◽  
Check Point ◽  
Imaging Findings ◽  
Check Point Inhibitors

The broad spectrum of cardiovascular adverse events related to immune check point inhibitors

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.S Andres ◽  
J Baksi ◽  
R Khattar ◽  
S.D Rosen ◽  
A.R Lyon
Keyword(s):  
Heart Failure ◽  
Adverse Effects ◽  
Adverse Events ◽  
Broad Spectrum ◽  
Checkpoint Inhibitors ◽  
Combined Therapy ◽  
Supraventricular Arrhythmias ◽  
Single Centre Study ◽  
Check Point Inhibitors ◽  
Ct Coronary Angiogram

Abstract Background Immunotherapy is one of the latest and most exciting developments in cancer treatment. Immune checkpoint inhibitors (ICI) have shown to have impressive positive results on several tumours such as melanoma, renal cancer and lung cancer, among others. Along with its benefits come the adverse effects which, concerning the heart, myocarditis is the most well-known and feared event. Yet, the spectrum of cardiovascular adverse events (CVAE) is much broader, ranging from heart failure to arrhythmias, but this has not been well documented until know. Objective Describe the broad spectrum of CVAE related to ICI Methods Observational retrospective, single centre study. We evaluated all the patients that have been referred to the cardio oncology (CO) unit and were under ICI treatment. The referred patients underwent a day case assessment with cardiovascular tests (blood tests, ECG, resting echocardiogram in all cases and MRI, stress echo or CT coronary angiogram if needed). The results were discussed in the multidisciplinary team meeting and the patients were then reviewed by one of the doctors in the team. The conclusions of the assessment were then communicated to the oncology team. Results From the year 2011 until December 2019, 71 patients receiving immunotherapy were referred to the CO unit. Three patients were excluded because they were referred for having an intracardiac tumour, leaving 68 for analysis. The first patient was referred in 2014 and during the first 3 years only 7 patients were reviewed in the CO unit. The frequency increased dramatically in 2017 to 17, 19 in 2018 and 25 in 2019. 21 patients were receiving Nivolumab, 24 on Ipilimumab, and 23 (34%) on combined therapy. The most frequent tumour was Melanoma (26/68, 38%). Regarding the CVAE: 22 patients (32%) were referred for investigtion of myocarditis. 6 had a diagnosis of definite myocarditis, 5 probable and 4 possible. Other CVAE (20/68, 29%) were the supraventricular arrhythmias including atrial fibrilation (20/68, 29%). 8 patients presented with non-inflammatory heart failure with new LVEF drop, 4 with chest pain, and 4 others with syncope. 1 patient developed pulmonary hypertension. Conclusions Myocarditis still remains the most frequent CVAE related to ICI, but the spectrum is broader than initially described. Supraventricular arrhythmias and non-inflammatory LVEF disfunction were very frequent in this series and we suspect that the incidence will increase as cardiologist and oncologists start considering them as probable adverse effects of this treatment. Funding Acknowledgement Type of funding source: None

Sign in / Sign up

Export Citation Format

Share Document