The positive effect of immune checkpoint inhibitor-induced thyroiditis on overall survival accounting for immortal time bias: a retrospective cohort study of 6596 patients

Street, Sarah E.; Chute, Donald F.; Strohbehn, Ian A.; Zhao, Sophia; Rengarajan, Michelle; Faje, Alexander T.; Seethapathy, Harish; Lee, M; Seethapathy, Rituvanthikaa; Drobni, Zsófia; Rahma, Osama E.; Neilan, Tomas G.; Sullivan, Ryan J.; Villani, Alexandra Chloé; Zubiri, Leyre; Mooradian, Meghan J.; Reynolds, Kerry L.; Sise, Meghan E.

doi:10.1016/j.annonc.2021.05.357

Cited by 25 publications

(27 citation statements)

References 6 publications

(6 reference statements)

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“…Previously, it was suggested that treatment with VEGFi is an inducer of thyroid injury, increasing the risk for irT with CPI exposure [ 12 ]. While the rate of irT is higher in our cohort than the commonly reported 20–30% [ 7 , 8 , 10 , 12 , 18 , 19 , 20 ], the incidence rate did not differ between patients who were treated with immunotherapy in the first-line treatment or after previous treatment with VEGFi. For patients with previous thyroid dysfunction on VEGFi we found a non-significant trend of increased irT risk (HR = 2.14, p = 0.08).…”

Section: Discussioncontrasting

confidence: 87%

“…To our knowledge, this is the largest cohort studied to evaluate irT in mRCC patients to date. Several studies have evaluated the prognostic value of irT in several cancer types with indeterminate findings [ 7 , 8 , 10 , 12 , 18 , 19 , 20 ]. We found a strong and significant association with survival in poor risk/High risk patients.…”

Section: Discussionmentioning

confidence: 99%

“…Prior studies have shown mixed results; two smaller studies found a protective association of irT on OS [ 7 , 12 ]. In contrast, another study found no such association in RCC with the limitation that other urologic malignancies were grouped together, despite the significant variability in clinical, molecular, and pathological characteristics [ 18 ]. Several studies in melanoma demonstrated that irT is predictive for survival [ 19 ], while others did not find any association [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

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Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma

Sagie

Gadot

Levartovsky

et al. 2022

Cancers

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Immune checkpoint inhibitors (CPI) are indicated for metastatic renal cell carcinoma (mRCC). Immune-related thyroiditis (irT), an immune-related adverse event (irAE), affects up to 30% of patients. We aimed to determine whether irT is associated with overall survival in mRCC. A retrospective cohort study of 123 consecutive patients treated with CPI for mRCC in a single center between 2015 and 2020 was conducted. Disease risk stratification was assessed by two methods: Heng criteria and a novel dichotomic stratification system to “Low risk” versus “High risk” adding number of metastatic sites. Thirty-eight percent of patients developed irT. In the general cohort, irT was not associated with a survival benefit. However, irT was associated with better survival in the poor risk group per Heng criteria (n = 17, HR = 0.25, p = 0.04) and in the novel “High risk” group (HR = 0.28, n = 42, p = 0.01), including after accounting for covariates in multivariate analysis (HR = 0.27, p = 0.003). Having any irAE was associated with improved survival in the whole cohort, with no significant correlation of any specific irAE, in either the whole cohort or the “High risk” group. We conclude that irT is an early and prevalent irAE, associated with prolonged survival in patients with poor/“High” risk mRCC.

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Section: Discussioncontrasting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma

Sagie

Gadot

Levartovsky

et al. 2022

Cancers

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“…While the occurrence of an immune-related adverse event such as AIN may threaten to derail effective cancer treatment, emerging evidence suggests that immune-related adverse events may be associated with improved overall survival. 52 Immune-related adverse events may be a marker of a “desirable” immune response, with higher-grade immune-related adverse events predicting or acting as a marker for a higher immunotherapy-objective response rate and longer progression-free survival in cancers such as renal cell carcinoma and non–small cell lung cancer. 53 It is unknown if specific immune-related adverse events such as AIN have the same association with mortality.…”

Section: Managementmentioning

confidence: 99%

Immune Checkpoint Inhibitors and Kidney Toxicity: Advances in Diagnosis and Management

2021

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Systematic efforts to wean patients off thyroid replacement (to confirm persistence) have, to our knowledge, not been made, although anecdotally we have not been successful in our attempts to discontinue hormone replacement therapy in such circumstances. Of note, thyroid dysfunction seems to be associated with a superior prognosis, although as with other toxicity–survival associations, time-dependent variables might be confounding 82 , 83 .…”

Section: Chronic Iraesmentioning

confidence: 99%

Immune-checkpoint inhibitors: long-term implications of toxicity

et al. 2022

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The development of immune-checkpoint inhibitors (ICIs) has heralded a new era in cancer treatment, enabling the possibility of long-term survival in patients with metastatic disease, and providing new therapeutic indications in earlier-stage settings. As such, characterizing the long-term implications of receiving ICIs has grown in importance. An abundance of evidence exists describing the acute clinical toxicities of these agents, although chronic effects have not been as well catalogued. Nonetheless, emerging evidence indicates that persistent toxicities might be more common than initially suggested. While generally low-grade, these chronic sequelae can affect the endocrine, rheumatological, pulmonary, neurological and other organ systems. Fatal toxicities also comprise a diverse set of clinical manifestations and can occur in 0.4–1.2% of patients. This risk is a particularly relevant consideration in light of the possibility of long-term survival. Finally, the effects of immune-checkpoint blockade on a diverse range of immune processes, including atherosclerosis, heart failure, neuroinflammation, obesity and hypertension, have not been characterized but remain an important area of research with potential relevance to cancer survivors. In this Review, we describe the current evidence for chronic immune toxicities and the long-term implications of these effects for patients receiving ICIs.

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The positive effect of immune checkpoint inhibitor-induced thyroiditis on overall survival accounting for immortal time bias: a retrospective cohort study of 6596 patients

Cited by 25 publications

References 6 publications

Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma

Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma

Immune Checkpoint Inhibitors and Kidney Toxicity: Advances in Diagnosis and Management

Immune-checkpoint inhibitors: long-term implications of toxicity

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