Experience of immune-related adverse events associated with ipilimumab and nivolumab in a single center.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 91-91 ◽  
Author(s):  
Bernardo Leon Rapoport ◽  
Teresa Smit ◽  
Ronwyn van Eeden
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Performance Status ◽  
Death Receptor ◽  
Endocrine System ◽  
Organ Systems ◽  
Anti Cancer ◽  
Life Threatening ◽  
Prompt Diagnosis ◽  
Cell Death Receptor

91 Background: Anti-programmed cell death receptor-1 (PD-1) and anti-CTLA4 antibodies represent an effective anti-cancer. Ipilimumab and nivolumab can induce immune-related adverse events (IrAEs). These IrAEs affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Life-threatening and fatal irAEs have been reported; adequate diagnosis and management are essential. Methods: A retrospective review of data from 40 patients (pts) records were used to describe the IrAE’s associated with 15 pts treated with ipilimumab and 25 pts treated with nivolumab. Results: A total of 40 pts (25 males and 15 females) were included in the analysis. The median age was 63 years (range 30 - 85 years). The performance status (PS) ranged from 0 to 2, with a median PS of 1. In total, 3 pts with metastatic melanoma, 18 with non small cell lung cancer (NSCLC), 2 with renal cell carcinoma and 2 with Hodgkin’s disease were treated with nivolumab and 15 with metastatic melanoma received ipilimumab. A total of 167 cycles of nivolumab (median = 4, range 1-16) and 60 cycles of ipilimumab (median = 4 cycles, range 1-4 cycles) were administered. Seven IrAEs are described in 19 pts treated with ipilimumab. These include endocrinopathy in 3 pts (hypophysitis in pt and hyphothyroidsm in 2 pts), colitis in 3 pts (1 required infliximab) and hepatitis in 1 pt. Among the pts treated with nivolumab 7 IrAEs were documented. These included pneumonitis in 2 pts, skin rash in 3 pts, mild diarrhea in 1 pt and mild uveitis in 1 pt. Additionally, 3 chest infections were documented including a case of pulmonary tuberculosis in a pt with NSCLC. Conclusions: Anti-PD1 and anti-CTLA4 antibodies can induce a plethora of irAEs. Colitis was more common with ipilimumab while pneumonitis more common with nivolumab. The knowledge of IrAE’s will allow prompt diagnosis and improve the management resulting in decreased morbidity.

Behcet’s-like syndrome following pembrolizumab: An immune-related adverse event associated with programmed death receptor-1 inhibitor therapy

2019 ◽  
Vol 26 (4) ◽  
pp. 995-999 ◽  
Author(s):  
Steffi Thomas ◽  
Chay Bae ◽  
Tabanor Joy-Ann ◽  
William Traverse
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Programmed Death ◽  
Organ Systems ◽  
Wide Range ◽  
The Right

Introduction The landscape for the treatment of metastatic melanoma has been revolutionized with the introduction immune checkpoint inhibitors. Immune checkpoint inhibitors have now become the standard of care for the treatment of cancers. These immune agents including programmed death receptor-1 inhibitors, programmed death-ligand 1 inhibitors and cytotoxic T-lymphocyte antigen-4 inhibitors have shown promising results but have been associated with numerous immune-related complications. Pembrolizumab, a programmed death receptor-1 inhibitor, has been associated with a number of immune-related adverse events affecting multiple organ systems including integument, ocular, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, and musculoskeletal system. Case report We present a case of an 88-year-old Caucasian male with metastatic melanoma of the face with metastasis to the right fifth cranial nerve and into the right cavernous sinus. He underwent resection of the melanoma and was placed on pembrolizumab at 2 mg/kg every three weeks. Interestingly, 24 months on pembrolizumab therapy, he developed corneal erosions, oral and genital ulcerations. Management and outcome Patient completed his 24 months of pembrolizumab and was started on prednisone and colchicine with improvement in his symptoms. At his follow-up eight months, he had recurrence of an oral ulcer. Discussion Here we present a rare case of an elderly male on pembrolizumab who suffered from corneal erosions, oral and genital ulcers, a syndrome similar to Behcet’s disease. Given that pembrolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the wide range immune-related adverse events including the possible Behcet’s-like syndrome presentation.

scholarly journals Immunotherapy for Metastatic Melanoma with Right Atrial Involvement in a Patient with Rheumatoid Arthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Zachary Benson ◽  
Sarah Gordon ◽  
Patricia Nicolato ◽  
Andrew Poklepovic
Keyword(s):  
Rheumatoid Arthritis ◽  
Heart Failure ◽  
Surgical Treatment ◽  
Autoimmune Disease ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
Response To Therapy ◽  
Right Atrial ◽  
Durable Response ◽  
Life Threatening

Prognosis for metastatic melanoma has improved significantly with the use of immune checkpoint inhibitors. Given improvements in survival, aggressive surgical treatment may be considered in patients with life-threatening complications from their disease that would not otherwise be considered in advanced disease. Patients with preexisting autoimmune diseases or prior immune-related adverse events from therapy are largely excluded from clinical trials. Concerns exist that immunotherapy in these patients could worsen autoimmune disease or increase the risk of developing additional immune-related adverse events on therapy. We present a case of a patient with rheumatoid arthritis that presented with obstructive heart failure secondary to melanoma that had metastasized to the right atrium. After aggressive surgical resection to stabilize him from his life-threatening heart failure, he was treated with ipilimumab, which was stopped due to an immune-related adverse event. He was then started on pembrolizumab and had a durable response to therapy. Aggressive surgical treatment should be considered in patients with a cancer that may respond to immunotherapy. Furthermore, some patients with preexisting autoimmune disease may be safely treated with checkpoint inhibition therapy, and patients with a severe immune toxicity from one class may successfully be treated with an alternate class.

scholarly journals Treatment Considerations for Patients with Unresectable Metastatic Melanoma Who Develop Pembrolizumab-Induced Guillain-Barré Toxicity: A Case Report

2020 ◽  
Vol 13 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Sivraj Muralikrishnan ◽  
Lara K. Ronan ◽  
Shodeinde Coker ◽  
Paula K. Rauschkolb ◽  
Keisuke Shirai
Keyword(s):  
Side Effects ◽  
Metastatic Melanoma ◽  
Performance Status ◽  
Subsequent Treatment ◽  
Improved Outcomes ◽  
Treatment Considerations ◽  
Prolonged Recovery ◽  
Life Threatening ◽  
Difficult Challenge ◽  
Guillain Barré

Immunotherapy has improved outcomes in many malignancies, most notably in melanoma, lung cancer, and bladder cancer. Understanding the side effects associated with these medications is an important part of managing our patients. Although fatigue, rash, and diarrhea are commonly reported side effects, it is important to be cognizant of rarer ones, such as neuropathy. Amongst the different neurological toxicities that have been reported in the literature, Guillain-Barré-like neuropathies are quite rare. However, the occurrence of such neuropathies in a patient can be life threatening. The problem this poses in treating cancers such as melanoma is that it eliminates an effective class of medication available to the patient, which can ultimately affect their prognosis. We present a case of a 65-year-old female with unresectable metastatic melanoma who developed Guillain-Barré-like neuropathy after two doses of pembrolizumab. Her clinical course was complicated by three separate hospitalizations over 3 months due to recurring bouts of neuropathy, which resulted in a significant decline in performance status and delay in subsequent treatment of her melanoma. Her prolonged recovery eventually resulted in progression of her melanoma nearly 1 year later, while off therapy. Instead of discontinuing immunotherapy completely, she agreed to a re-challenge with ipilimumab. After one dose, her melanoma regressed and continues to show a sustained response nearly 1 year after treatment without any signs of relapse in her neuropathy. Guillain-Barré toxicity resulting from immune checkpoint inhibition poses a difficult challenge to an oncologist who is determining the next line of treatment for patients with unresectable metastatic melanoma that have progressed while off therapy and who have no targetable mutations. Our case raises the question of whether a re-challenge with a different class of immunotherapy agent is a reasonable option.

scholarly journals Rapid onset type-1 diabetes and diabetic ketoacidosis secondary to nivolumab immunotherapy: a review of existing literature

2019 ◽  
Vol 12 (8) ◽  
pp. e229568 ◽  
Author(s):  
Hafez Mohammad Ammar Abdullah ◽  
Radowan Elnair ◽  
Uzma Ikhtiar Khan ◽  
Muhammad Omar ◽  
Oscar L Morey-Vargas
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Ketoacidosis ◽  
Death Receptor ◽  
Rapid Onset ◽  
Acute Onset ◽  
Fulminant Type 1 Diabetes ◽  
Life Threatening ◽  
Cell Death Receptor ◽  
Fulminant Type

Nivolumab is a programmed cell death receptor (PD-1) inhibitor that is increasingly used for various malignancies, both as a first line agent and as salvage therapy. Being a PD-1/PD-1 ligand checkpoint inhibitor, it is known to cause autoimmune inflammation of various organs and has been associated with thyroiditis, insulitis, colitis, hepatitis and encephalitis to name a few. There are increasing reports of nivolumab leading to acute onset fulminant type 1 diabetes and diabetic ketoacidosis (DKA). We present a case of a 68-year-old man who developed DKA after 2 doses of nivolumab for metastatic melanoma. He was found to have type 1 diabetes, but no diabetes related antibodies were positive. He recovered from diabetes and continues to use insulin 1 year after his diagnosis. This case and associated review illustrates the importance of educating and monitoring patients who start nivolumab therapy regarding this potentially life threatening complication.

scholarly journals Safety of systemic anti-cancer treatment in oncology patients with non-severe COVID-19: a cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
C. van Marcke ◽  
N. Honoré ◽  
A. van der Elst ◽  
S. Beyaert ◽  
F. Derouane ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Adverse Events ◽  
Cancer Treatment ◽  
Performance Status ◽  
Rt Pcr ◽  
Bleeding Events ◽  
Oncology Patients ◽  
Treatment Delays ◽  
Ambulatory Oncology ◽  
Anti Cancer

Abstract Background The viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is an important matter in daily practice. Methods ONCOSARS-1 was a single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were prospectively included. All patients (n = 363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the first peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to retrospectively determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients. Results Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (P < 0.001). This association remained significant (odds ratio (OR) 4.1, P = 0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (P < 0.001). Median duration of treatment interruption was similar between the two groups: 14 and 11 days, respectively. Febrile neutropenia, infections unrelated to COVID-19, and bleeding events occurred at a low rate in the SARS-CoV-2-positive patients. Conclusion Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.

scholarly journals Acute colonic pseudo-obstruction following nivolumab and ipilimumab combination therapy for metastatic melanoma

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Mami Ishibashi ◽  
Yoshihiro Ishida ◽  
Atsushi Otsuka ◽  
Shuji Yamamoto ◽  
Kenji Kabashima
Keyword(s):  
Combination Therapy ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
High Dose ◽  
Prompt Treatment ◽  
Prompt Diagnosis

Immune-related adverse events (irAEs) are commonly observed in patients treated with immune checkpoint inhibitors (ICI), and prompt diagnosis and treatment of irAEs is of utmost importance. Gastrointestinal (GI) events are among the most frequent irAEs and the hallmark symptom is diarrhea. Intestinal hypomotility as irAEs is exceedingly rare, and needs wider recognition given that the presentation is insidious.Here, we report a case of 79-year-old woman with metastatic melanoma under nivolumab and ipilimumab combination therapy. She developed ileus symptom, and was diagnosed with acute colonic pseudo-obstruction. The symptom relieved soon after administering high-dose prednisolone five days after the onset. ICI therapy was discontinued.Intestinal hypomotility as GI irAEs is exceedingly rare and there have been five reported cases to our knowledge. In reviewing past cases, we speculate that the prompt initiation of corticosteroids resulted in a favorable outcome. Our case illustrates that early recognition of these rare irAEs is essential in order to ensure prompt treatment.

Ipilimumab in the common daily practice: Feasibility, safety, and efficacy in heavily pretreated metastatic melanoma patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20002-e20002
Author(s):  
A. Di Giacomo ◽  
R. Danielli ◽  
L. Calabrò ◽  
M. Guidoboni ◽  
C. Miracco ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Clinical Benefit ◽  
Performance Status ◽  
Daily Practice ◽  
World Health ◽  
Induction Phase ◽  
Heavily Pretreated ◽  
The Common ◽  
Grade 3

e20002 Background: Effective anti-tumor responses are being observed in metastatic melanoma (MM) patients (pts) with the anti-CTLA-4 antibody Ipilimumab (Ipi) in clinical trials; however no data support the feasibility and clinical effectiveness of Ipi use in the daily practice. We report a single Institution experience utilizing Ipi within a compassionate program for MM pts. Methods: 27 stage III (2) or IV (25) pts (14 males, 13 females), median age 55 (23–77) years, ECOG performance status 0- 1, with MM (23 cutaneous, 3 uveal, 1 mucosal) progressing to 3 median (1–5) systemic therapies for metastatic disease received Ipi. Eight pts had evidence (6) or history (2) of brain metastases and 11 elevated (>1x upper limit of normal [ULN]) LDH. In the induction phase (IF) pts received Ipi (10 mg/kg i.v.) q3 weeks (wks) x 4 cycles; after a 12 wks rest treatment was repeated q12 wks in the maintenance phase (MF). Tumor assessment (TA) per modified World Health Organization criteria was performed at baseline, week (wk) 12 (±2) and wk 24, then every 12 wks. Adverse Events (AE) and immune related AE (irAE) were collected according to Common Terminology Criteria for Adverse Events version 3.0. Results: All pts received at least one Ipi dose, and 18/27 completed the IF. Of the remaining 9 pts, 4 are completing the IF and 5 were withdrawn for AE severity (3 pts) or disease progression (2 pts). Eight pts entered the MF. TA at wk 12 showed partial response (PR) in 1/18 or stable disease (SD) in 5/18 pts. TA at wk 24 showed PR and SD in 3/8 and 5/8 pts, respectively, with an ongoing clinical benefit (SD + PR + CR) of 34% (8/23 pts); these pts are still on treatment. Slow, steady declines in tumor volume and appearance of new lesions with subsequent shrinking of total tumor burden has been observed. One patient had Grade 3 AE (myocardial infarction) and 2 pts had Grade 3 irAE (diarrhoea). Excluding pts who are in IF, to date median overall survival is 27 wks (19–39). Conclusions: Ipi treatment is feasible, safe and clinically effective also in the common daily practice and in heavily pretreated, progressing, MM pts. A sizable proportion of these pts experiences durable clinical benefit. No significant financial relationships to disclose.

scholarly journals Gastrointestinal disorders as immune-related adverse events

2021 ◽  
Author(s):  
Daniele Balducci ◽  
Claudia Quatraccioni ◽  
Antonio Benedetti ◽  
Marco Marzioni ◽  
Luca Maroni
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Programmed Cell Death 1 ◽  
Anti Cancer ◽  
Life Threatening

Immune checkpoint inhibitors, such as cytotoxic T-lymphocyte antigen 4 inhibitors, programmed cell death 1 inhibitors and programmed cell death-ligand 1 inhibitors, have recently emerged as novel drugs in the anti-cancer therapy. Their use in different types of advanced cancer has shown good results and an increase in survival rates. However, immune-related adverse events (irAEs) are frequent and often require special care. IrAEs may affect all the organs, but they are most commonly seen in skin, lungs, endocrine glands and in the gastrointestinal tract where small bowel, colon, the liver and/or the pancreas can be involved. Despite being usually mild and self-resolving, irAEs may present in severe and life-threatening forms, causing the withdrawal of anti-cancer therapy. IrAEs, therefore, represent a challenging condition to manage that often requires the cooperation between the oncologists and the gastroenterologists in order to identify and treat them adequately.

Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab

2012 ◽  
Vol 30 (21) ◽  
pp. 2691-2697 ◽  
Author(s):  
Jeffrey S. Weber ◽  
Katharina C. Kähler ◽  
Axel Hauschild
Keyword(s):  
Adverse Effects ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
Cytotoxic T Lymphocyte ◽  
Tumor Regression ◽  
Early Recognition ◽  
Tumor Burden ◽  
Initial Increase ◽  
Life Threatening ◽  
Kinetics Of

Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152)—ipilimumab and tremelimumab—have been investigated in metastatic melanoma and other cancers and have shown promising results. Recently, ipilimumab was approved by the US Food and Drug Administration for the treatment of metastatic melanoma. We review the literature on managing the adverse effects and kinetics of tumor regression with ipilimumab and provide guidelines on their management. During treatment with these antibodies, a unique set of adverse effects may occur, called immune-related adverse events (irAEs). These include rashes, which may rarely progress to life-threatening toxic epidermal necrolysis, and colitis, characterized by a mild to moderate, but occasionally also severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab. Early recognition of irAEs and initiation of treatment are critical to reduce the risk of sequelae. Interestingly, irAEs correlated with treatment response in some studies. Unique kinetics of response have been observed with CTLA-4 blockade with at least four patterns: (1) response in baseline lesions by week 12, with no new lesions seen; (2) stable disease, followed by a slow, steady decline in total tumor burden; (3) regression of tumor after initial increase in total tumor burden; and (4) reduction in total tumor burden during or after the appearance of new lesion(s) after week 12. We provide a detailed description of irAEs and recommendations for practicing oncologists who are managing them, along with the unusual kinetics of response associated with ipilimumab therapy.

scholarly journals Lupus Vasculitis: An Overview

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1626
Author(s):  
Patrizia Leone ◽  
Marcella Prete ◽  
Eleonora Malerba ◽  
Antonella Bray ◽  
Nicola Susca ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Pulmonary Hemorrhage ◽  
Small Vessels ◽  
Mild Disease ◽  
System Disease ◽  
Organ Systems ◽  
Life Threatening ◽  
Prompt Diagnosis

Lupus vasculitis (LV) is one of the secondary vasculitides occurring in the setting of systemic lupus erythematosus (SLE) in approximately 50% of patients. It is most commonly associated with small vessels, but medium-sized vessels can also be affected, whereas large vessel involvement is very rare. LV may involve different organ systems and present in a wide variety of clinical manifestations according to the size and site of the vessels involved. LV usually portends a poor prognosis, and a prompt diagnosis is fundamental for a good outcome. The spectrum of involvement ranges from a relatively mild disease affecting small vessels or a single organ to a multiorgan system disease with life-threatening manifestations, such as mesenteric vasculitis, pulmonary hemorrhage, or mononeuritis multiplex. Treatment depends upon the organs involved and the severity of the vasculitis process. In this review, we provide an overview of the different forms of LV, describing their clinical impact and focusing on the available treatment strategies.

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