Improved survival in patients with thyroid function test abnormalities secondary to immune-checkpoint inhibitors

2020 ◽  
Author(s):  
Joana Lima Ferreira ◽  
Cláudia Costa ◽  
Bernardo Marques ◽  
Sofia Castro ◽  
Margarida Victor ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Thyroid Function Test ◽  
Function Test

scholarly journals Incidence of Thyroid Function Test Abnormalities in Patients Receiving Immune‐Checkpoint Inhibitors for Cancer Treatment

2018 ◽  
Vol 23 (10) ◽  
pp. 1236-1241 ◽  
Author(s):  
Nisha Subhash Patel ◽  
Anais Oury ◽  
Gregory A. Daniels ◽  
Lyudmila Bazhenova ◽  
Sandip Pravin Patel
Keyword(s):  
Cancer Treatment ◽  
Thyroid Function ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Thyroid Function Test ◽  
Function Test

scholarly journals OR18-06 Thyroid Function Test Abnormalities Secondary to Immune-Checkpoint Inhibitors: A Marker of Survival?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Joana Lima Ferreira ◽  
Cláudia Fernandes Costa ◽  
Sofia Castro ◽  
Joana Oliveira ◽  
Ana Paula Santos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Thyroid Function ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Tumor Staging ◽  
Thyroid Function Test ◽  
Control Group ◽  
Function Test ◽  
Primary Neoplasm

Abstract Immune-checkpoint inhibitors (ICI) are monoclonal antibodies which target molecules to enhance antitumor response. Several adverse events have been described and the major ICI-related endocrinopathies are thyroid dysfunction and hypophysitis. Its occurrence has been associated with increased survival. A retrospective study of adult patients treated with ICI between March 2014 and September 2019 at an oncologic centre was performed to evaluate the impact of thyroid function test abnormalities (TFTA) in their prognosis. We excluded patients without regular monitoring of thyroid function, with previous thyroid or pituitary disease (including medical and surgical treatments), previous head/neck radiotherapy and who performed only one ICI cycle. Clinical data of all patients were examined independently by two Endocrinologists. Survival analysis was performed using the Kaplan-Meier method. Cox regression was used to evaluate associations between the occurrence of TFTA and the outcome of overall survival (OS). It was adjusted for sex, age, primary neoplasm, tumor staging and ICI. All analyses were performed using IBM-SPSS v.25 and a level of significance α=0.05 was noted. We included 161 of 205 patients, with a median age of 65 years [Interquartile range (IQR) 15] and 67% male. Most patients had melanoma (52%) and lung cancer (43%). Globally, 86, 59 and 25 patients were under pembrolizumab, nivolumab and ipilimumab, respectively. Median duration of ICI treatment was 4.4 months (IQR 7.7) and median total follow-up was 11.4 months (IQR 11.2). New onset TFTA was diagnosed in 18% of patients, at median age of 65 years (IQR 20) and 55% male. Almost half (45%) had primary hypothyroidism, 28% had central hypothyroidism and 13.8% had biphasic thyroiditis and thyrotoxicosis, each. Most TFTA (79%) occurred under pembrolizumab and nivolumab. Grade 2 CTCAE was the most frequently reported. None of the events led to ICI suspension. Patients with TFTA underwent a significant higher number of ICI cycles than control group [median 11 cycles (IQR 20) vs 7 (IQR 11), p=0.017] and had a higher period under ICI (median of 7.6 months (IQR 13.8) vs 4.2 (IQR 7.7), p=0.026). Comparison between TFTA patients and control group did not reveal statistical differences in patients’ age and sex, primary neoplasm, tumor staging and ICI. Overall survival was significantly higher in patients that developed TFTA during treatment with ICI, comparing to the control group (mean OS 3.62 years vs 1.92 years, p=0.033). The risk of mortality was higher for the control group, approximately 3 times, considering the adjustment for the covariates (HR 2.94, 95%CI=1.18 to 7.34, p=0.021). Overall survival was not affected by the covariates. Our study shows that patients under ICI that develop primary or central thyroid dysfunction had an improved survival. In these patients, the occurrence of TFTA could be a marker of a better response to ICI.

Evaluation of tolerability and reactions of immune checkpoint inhibitors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14605-e14605 ◽  
Author(s):  
Ozlem Nuray Sever ◽  
Ozlem Sonmez ◽  
Osman Gokhan Demir
Keyword(s):  
Monoclonal Antibodies ◽  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Interruption ◽  
Ease Of Use ◽  
Treatment Change ◽  
Function Test ◽  
Cessation Of Treatment

e14605 Background: Immunotherapies have revolutionized the treatment of cancer, especially in recent years. Today, there are anti-CTLA-4 antibodies and PD-L1 monoclonal antibodies which are active in use as checkpoint inhibitors. Side effects of these agents have a different spectrum in the form of immuno-related side effects. Methods: In this study, we aimed to evaluate the side effect and tolerability in patients treated with immune checkpoint inhibitors in our clinic. Results: 32 patients who were treated with PD-L1 monoclonal antibodies between August 2015 and January 2017 were screened retrospectively in our clinic. Six of the cases had immuno-related side effects (18.75%). 2 patients had a elevated liver function test. Both patients were diagnosed with NSCLC. In both of them, elevation was detected in the second course of nivolumab treatment, and the USG and hepatitis markers of the patients were normal. Enzymes returned to normal after treatment interruption. In a patient diagnosed with malignant melanoma that receiving pembrolizumab colitis was developed after 3th cycles of the therapy. The treatment of the patient who recovered after steroid administration and treatment interruption continued until the 8th cure. In the third cure of the patient with NSCLC, when nivolumab was used pneumonitis was diagnosed. Steroid treatment was applied for 2 weeks. Our patient continued to use nivolumab for up to 22 cycles. In our patient with malign melanoma that treated with pembrolizumab autoimmune thyroiditis developed. We started prednisolone treatment. After recovery our patient's treatment continued. In one of our patient who was diagnosed with malign melanoma, after the second cure of the treatment, diffuse edema and shortness of breath due to heart failure was detected. Echocardiography revealed a low ejection fraction. Methylprednisolone was started by cessation of treatment. Control ejection fractions normalized. Conclusions: İmmuno-related side effects were regarded as manageable side effects and no treatment change was needed. Immune Checkpoint inhibitors, which have been shown to be useful for survival every day, are proceeding to take a favorable position in the treatment of cancer with ease of use and lack of side effects.

Patterns of thyroid dysfunctions during treatment with immune checkpoint inhibitors (ICI) in 59 solid cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18567-e18567
Author(s):  
Yong Jiang ◽  
Li Yang ◽  
Yin Han ◽  
Yongshen Zhang ◽  
Feng-Ming Kong
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Thyroid Function ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Thyroid Dysfunctions

e18567 Background: Immune checkpoint inhibitors (ICI) have now become the mainstay treatment in patients with many kinds of cancers. Thyroid dysfunction as the most common endocrine toxicity is poorly understood. This study aimed to report hypothyroidism and exam its changing dynamtic in our first series of patients treated with ICI. Methods: This is a retrospective study. Patients received nivolumab or pembrolizumab between July 2018 and December 2019 were considered. Patient must have euthyroidism within the 3 months before immunotherapy and those had previous use of levothyroxine were excluded. They were monitored by thyroid function tests every cycle until stopping ICI. Patients must have received at least 3 cycles of antibody treatment. Results: Among 89 patients treated, 59 met the inclusion criteria. There were 33 males, 26 females, including 26 (44.1%) nivolumab, and 33 (55.9%) pembrolizumab. Median age was 62 years [range: 27-88]). Cancer diagnoses observed were non small cell lung cancer 17(28.8%), small cell lung cancer 4 (6.8%),liver cancer 9 (15.3%), head and neck cancer 5 (8.5%), esophageal cancer4 (6.8%) colon cancer 3 (5.1%), nasopharygeal carcinoma 3 (5.1%) melanoma 3 (5.1%) and other cancers 11(18.6%). There were 9 patients (15.3%) developed a thyroid dysfunction, including 5 females. Four patients had thyrotoxicosis (median onset: 8 weeks) followed by hypothyroidism. There were three types of thyroid dysfunctions: the first type patients 3 (33.3%) had a brief time period of TSH flair (peak 17.4-57.8) after the first cycle of ICI, followed by TSH dramatic drop companied with rising fT4, which usually returned to normal level during 3-4 cycles of . The other 4 patients (44.4%) with thyroid dysfunction presented with remarkably elevated TSH (15.43-125.2) after 3.5-10 months’ treatment, followed by hypothyroidism development with a need of levothyroxine. The remaining 1 patient had a third type of thyroid dysfunction with elevated TSH, elavated more while the treatment continue, the patient should be given levothyroxine as soon as possible. Additionally, 1 patient developed hypopituitarism presented with both low level of TSH and fT4 after 10 month treatment. There was no significant difference in patient characteristics between patients with hypothyroidism and those without. Conclusions: There are heterogeneity in thyroid function and hypothyroidism after ICI. Before more experience is gained, frequent monitoring of thyroid function during ICI is warranted for prompt management of the hypothyroidism.

THYROID DYSFUNCTION, RECOVERY, AND PROGNOSIS IN MELANOMA PATIENTS TREATED WITH IMMUNE CHECKPOINT INHIBITORS: A RETROSPECTIVE REVIEW

2020 ◽  
Vol 26 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Mazen Al Mushref ◽  
Paul A. Guido ◽  
Frances A. Collichio ◽  
Dominic T. Moore ◽  
David R. Clemmons
Keyword(s):  
Thyroid Function ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Function Tests ◽  
Melanoma Patients ◽  
Recovery Group ◽  
Stimulating Hormone

Objective: To describe thyroid dysfunction, factors associated with thyroid recovery, and survival in melanoma patients treated with immune checkpoint inhibitors that developed thyroid immune-related adverse events (irAEs). Methods: This was a retrospective study in a tertiary center from 2010–2017. We reviewed the charts of patients with melanoma that developed thyroid dysfunction after checkpoint inhibitor therapy. Cases with thyroid irAEs were grouped by recovery of thyroid function at 1 year. We collected a timeline of thyroid function tests, medication exposure, and survival and compared variables between the groups. We studied survival in comparison to a matched group without thyroid dysfunction. Results: A total of 186 melanoma patients received checkpoint inhibitors, and 17 (9%) had thyroid irAEs. Median time to abnormal thyroid-stimulating hormone was 38 days and followed a pattern of thyroiditis. Seven of 17 had thyroid recovery. In the no-recovery group, free thyroxine (T4) was often above 2 ng/dL (5/10 in no recovery, 0/7 in recovery; P = .04). In the recovery group, irAE grade was significantly lower, with 7/7 grade 1 ( P = .004). Exposure to glucocorticoids was associated with recovery (3/10 in no recovery, 6/7 in recovery; P = .049). There was no difference in overall survival between the thyroid dysfunction group and controls, or between those that received glucocorticoids or not. Conclusion: Certain aspects of thyroid irAEs may correlate with thyroid recovery, including grade 1 thyroid irAEs, exposure to glucocorticoids, and peak free T4 levels less than 2 ng/dL. Thyroid irAEs did not appear to be associated with change in survival nor did exposure to glucocorticoids. Abbreviations: ASCO = American Society of Clinical Oncology; CTLA-4 = cytotoxic T-lymphocyte–associated protein 4; irAE = immune-related adverse event; PD-1 = programmed cell death protein 1; T4 = thyroxine; TSH = thyroid-stimulating hormone

scholarly journals Myxoedema coma caused by immunotherapy-related thyroiditis and enteritis

2021 ◽  
Vol 2021 ◽  
Author(s):  
Darran Mc Donald ◽  
Eirena Goulden ◽  
Garret Cullen ◽  
John Crown ◽  
Rachel K Crowley
Keyword(s):  
Malignant Melanoma ◽  
Thyroid Function ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Reactions ◽  
Checkpoint Inhibitors ◽  
Thyroid Function Tests ◽  
Absorption Test ◽  
Function Tests ◽  
Painless Thyroiditis

Summary Thyroid dysfunction is among the most common immune-related adverse reactions associated with immune checkpoint inhibitors. It most commonly manifests as painless thyroiditis followed by permanent hypothyroidism. This usually causes mild toxicity that does not interfere with oncological treatment. In rare instances, however, a life-threatening form of decompensated hypothyroidism called myxoedema coma may develop. We present a case of myxoedema coma in a woman in her sixties who was treated with a combination of CTLA-4 and PD-1 immune checkpoint inhibitors; for stage four malignant melanoma. She became hypothyroid and required thyroxine replacement after an episode of painless thyroiditis. Six months after the initial diagnosis of malignant melanoma, she presented to the emergency department with abdominal pain, profuse diarrhoea, lethargy and confusion. She was drowsy, hypotensive with a BP of 60/40 mmHg, hyponatraemic and hypoglycaemic. Thyroid function tests (TFTs) indicated profound hypothyroidism with a TSH of 19 mIU/L, and undetectable fT3 and fT4, despite the patient being compliant with thyroxine. She was diagnosed with a myxoedema coma caused by immune-related enteritis and subsequent thyroxine malabsorption. The patient was treated with i.v. triiodothyronine (T3) and methylprednisolone in the ICU. While her clinical status improved with T3 replacement, her enteritis was refractory to steroid therapy. A thyroxine absorption test confirmed persistent malabsorption. Attempts to revert to oral thyroxine were unsuccessful. Unfortunately, the patient’s malignant melanoma progressed significantly and she passed away four months later. This is the first reported case of myxoedema coma that resulted from two distinct immune-related adverse reactions, namely painless thyroiditis and enterocolitis. Learning points Myxoedema coma, a severe form of decompensated hypothyroidism is a rare immunotherapy-related endocrinopathy. Myxedema coma should be treated with either i.v. triiodothyronine (T3) or i.v. thyroxine (T4). Intravenous glucocorticoids should be co-administered with thyroid hormone replacement to avoid precipitating an adrenal crisis. Thyroid function tests (TFTs) should be monitored closely in individuals with hypothyroidism and diarrhoea due to the risk of thyroxine malabsorption. A thyroxine absorption test can be used to confirm thyroxine malabsorption in individuals with persistent hypothyroidism.

Incidence of thyroid function test abnormalities in patients receiving immune checkpoint inhibitor therapy for cancer: A single institution retrospective review.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14569-e14569
Author(s):  
Nisha Subhash Patel ◽  
Anais Oury ◽  
Lyudmila Bazhenova ◽  
Gregory A. Daniels ◽  
Sandip Pravin Patel
Keyword(s):  
Thyroid Function ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Thyroid Function Test ◽  
Single Institution ◽  
Function Test ◽  
Checkpoint Inhibitor Therapy ◽  
Thyroid Abnormalities ◽  
New Onset

e14569 Background: With the advent of immune-checkpoint inhibitor (ICI) therapy, thyroid function test abnormalities (TFTA) are common with reported incidence range of 2-15%. Our aim was to describe the incidence of TFTAs retrospectively in patients (pts) on ICI therapy. Methods: 285 pts reviewed (178 male, 107 female; ages 16-94) of which 218 had no baseline TFTA, 61 had baseline TFTAs, and 6 had thyroidectomy (excluded). Pts received at least one dose of ipilimumab (I) and/or nivolumab (N) or pembrolizumab (P). Post-treatment TFTA was classified according to definitions of thyroid abnormalities when possible. Results: A total of 35% (76/218) pts had new onset TFTAs on ICI. Of note, 70.5% (43/61) had baseline TFTA that were exacerbated by ICI. Median time to new onset or exacerbated baseline TFTA were 46 & 33 days respectively. Of note, 65% (20/31) of pts on both I+N had new onset TFTA, compared to 31.3% (15/48) with I, 31.5% (28/89) N, 26% (13/50) P. Conclusions: Incidence of TFTAs with ICI was higher than expected in our pts. Pts with baseline TFTA and/or I+N combination therapy had higher incidence of TFTA than one agent ICI therapy. In conclusion, we recommend more frequent evaluation of TFT in the first two months, especially in those with baseline TFTA. [Table: see text]

scholarly journals SAT-463 Thyrotoxicosis from Nivolumab in a Patient with Preexisting Graves’ Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Preethi Polavarapu ◽  
Padmaja Akkireddy
Keyword(s):  
Adverse Events ◽  
Thyroid Function ◽  
Autoimmune Thyroiditis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Graves Disease ◽  
Thyroid Function Tests ◽  
Free T4

Abstract Introduction Thyroid dysfunction is one of the common immune-related adverse events associated with immune checkpoint inhibitors like Nivolumab. Thyroiditis or primary hypothyroidism is the most commonly reported presentation. Graves’ disease is less frequently reported. We report a case of preexisting Graves’ disease patient, on antithyroid meds who developed thyrotoxicosis followed by hypothyroidism after receiving Nivolumab therapy. Case 66 y/o female patient with newly diagnosed metastatic melanoma presented to us for evaluation of abnormal thyroid test after her second cycle of Nivolumab. She has a long-standing history of Graves’ disease and has been on methimazole since her diagnosis. Her baseline thyroid labs before the start of Nivolumab were within normal limits (on methimazole 2.5 mg daily). She presented with weight loss, palpitations, and tremors four weeks after the start of Nivolumab. On exam, she was tachycardic with tremors noted to outstretched hands and had diffusely enlarged thyroid. Repeat lab work done before her second cycle revealed suppressed TSH 0.02 (0.4-4.5 uIU/ml) with elevated free T4 and T3. Her TSI titers were elevated. Methimazole dose was increased to 10 mg daily, and follow up labs done in a month revealed TSH of 89 uIU/ml, Free T4 0.16 (0.76-1.8 ng/dl). Methimazole was completely stopped at this time. She continued to have elevated TSH despite being off of methimazole for more than a month, concerning for the development of hypothyroidism. She was started on levothyroxine, after which labs returned to normal. The patient continued on immunotherapy during this period. Discussion Immune checkpoint inhibitors have been increasingly used for cancer therapy. Endocrinopathies are the most common immune-related adverse events associated with the use of these agents, with thyroid dysfunction being more common. Our patient had well-controlled Graves’ disease and was on a stable dose of methimazole for years. She developed autoimmune thyroiditis four weeks after receiving immunotherapy and subsequently developed hypothyroidism. The literature search did not reveal cases of autoimmune thyroiditis in a patient with preexisting Graves’ disease. One study reported that the timeline for developing the thyrotoxic phase is five weeks, which is followed by the rapid development of either euthyroid or hypothyroid phase. Management during the thyrotoxic phase is usually beta-blockers. Current guidelines recommend checking thyroid function test before initiation of therapy and every two weeks after the diagnosis of thyrotoxicosis until they become euthyroid or hypothyroid. Our case illustrates that patients with preexisting Graves’ disease can develop thyroiditis after receiving immune checkpoint inhibitors, and hence, frequent monitoring with thyroid function tests is needed.

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