So slow, so fast, a case of nivolumab-induced hypothyroidism with subsequent rhabdomyolysis

Immunotherapy ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 625-628 ◽  
Author(s):  
Kamelah Abushalha ◽  
Sawsan Abulaimoun ◽  
Peter T Silberstein
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Death ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Thyroid Function Tests ◽  
Conventional Chemotherapy ◽  
Case Presentation ◽  
Normal Thyroid ◽  
Normal Thyroid Function ◽  
Programmed Cell Death 1

Background: Immunotherapy has revolutionized the treatment of cancer, but this has not come without a cost. Although immune checkpoint inhibitors are less toxic than conventional chemotherapy, they are associated with more frequent autoimmune side effects. Case presentation: We report a case of a patient with metastatic renal cell carcinoma who was treated with nivolumab and subsequently developed treatment related hypothyroidism with consequent rhabdomyolysis. Treatment with thyroxine resulted in resolution of the symptoms. Because of normal thyroid function tests before initiating nivolumab therapy and the absence of any other causes of hypothyroidism, it was safe to extrapolate a causal relationship between nivolumab and hypothyroidism. To date, this is the first reported case of a programmed cell death-1 inhibitor causing hypothyroidism, severe enough to induce rhabdomyolysis. Conclusion: Patients on nivolumab and other PD-1 inhibitors should be monitored and screened regularly for immune-related adverse events.

scholarly journals Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A841-A841
Author(s):  
Alessandro Brancatella ◽  
Isabella Lupi ◽  
Lucia Montanelli ◽  
Debora Ricci ◽  
Nicola Viola ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Checkpoint Inhibitors ◽  
Thyroid Volume ◽  
Clinical Severity ◽  
Response To Treatment ◽  
Thyroid Function Tests ◽  
Thyroid Ultrasound ◽  
Normal Thyroid ◽  
Normal Thyroid Function

Abstract Context: Thyrotoxicosis is a common immune-related adverse event in patients treated with PD1 or PD-L1 checkpoint inhibitors. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy is missing, as are data on response to treatment and follow-up. Objectives: To better characterize the thyrotoxicosis secondary to immune checkpoint inhibitors, gaining insights into pathogenesis and informing management. Methods: We conducted a prospective cohort study of 20 consecutive patients who had normal thyroid function before starting immunotherapy and then experienced thyrotoxicosis upon PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, scintigraphy, and longitudinal thyroid function tests. Results: Five patients had normal scintigraphic uptake (Sci+), no serum antibodies against the TSH receptor, and remained hyperthyroid throughout follow-up. The other 15 patients had no scintigraphic uptake (Sci-) and experienced destructive thyrotoxicosis followed by hypothyroidism (N= 9) or euthyroidism (N= 6). Hypothyroidism was more readily seen in those with normal thyroid volume than in those with goiter (P= 0.04). Among Sci- subjects, a larger thyroid volume was associated to a longer time to remission (P<0.05). Methimazole (MMI) was effective only in Sci+ subjects (P<0.05). Conclusions: Administration of PD1 or PD-L1 blocking antibodies may induce two different forms of thyrotoxicosis that appear similar in clinical severity at onset: a type 1 characterized by persistent hyperthyroidism that requires treatment with MMI, and a type 2 characterized by destructive and transient thyrotoxicosis that evolves to hypo- or eu-thyroidism. Thyroid scintigraphy and ultrasound help differentiating and managing these two forms of iatrogenic thyrotoxicosis

Aggravation of depigmentation for a non-small-cell lung cancer patient with pre-existing vitiligo using anti-programmed cell death-1 therapy: case report

Immunotherapy ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 175-181 ◽  
Author(s):  
Yinghui Xu ◽  
Yangyang Cai ◽  
Jianjiao Zu ◽  
Xu Wang ◽  
Yizhuo Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Adverse Events ◽  
Cancer Patient ◽  
Immune Checkpoint Inhibitors ◽  
Lung Cancer Patient ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Cell Death 1

Immune checkpoint inhibitors can enhance the antitumor activity of the immune system by mainly promoting CD8+ T lymphocyte immune function. However, they can also induce immune-related adverse events, especially skin toxicity. Some studies found that patients with autoimmune or inflammatory disease are susceptible to immune checkpoint inhibitors and were associated with a significantly increased risk of immune-related adverse events. In our present report, we described a newly diagnosed non-small-cell lung cancer patient who suffered from focal vitiligo for approximately ten years and was treated with the anti-programmed cell death-1 receptor antibody camrelizumab (SHR-1210), which accelerated the aggravation of depigmentation of the skin over the whole body in just half a year.

scholarly journals PD-L1, an Important Immune Checkpoint Regulator, Is Suppressed by miR-34a in Head and Neck Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Kenjiro Higashi ◽  
Takenori Ogawa ◽  
Yuriko Saiki ◽  
Tomohiko Ishikawa ◽  
Yuta Kobayashi ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Head And Neck ◽  
Cell Lines ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Expression Levels ◽  
Programmed Cell Death 1 ◽  
Hnscc Cell

Abstract Background: Key molecules regulating the immune checkpoint have shed light on the efforts to control several cancers. Recently, immune checkpoint inhibitors for cancer therapy such as antibodies against programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA4) have been developed. In head and neck squamous cell carcinomas (HNSCCs), such immune checkpoint inhibitors have come into clinical use and are expected to improve patients’ prognoses. Recently, miR-34a has been shown to be a downstream micro RNA of TP53 that regulates PD-L1 in several types of cancer. To reveal the correlations between miR-34a and PD-L1 in HNSCCs in terms of clinical significance, we analyzed 19 HNSCC cell lines.Methods: We measured the expression levels of miR-34a and PD-L1 in 10 HNSCC cell lines as well as in 9 of their derived acquired cisplatin (CDDP) resistant cell lines by qRT-PCR and Western blotting. Results were further analyzed by their TP53 statuses. We also investigated the changes in PD-L1 expression levels after miR-34a precursor- or inhibitor-mediated forced expression or suppression in HNSCC cell lines. Results: We observed inverse correlations between both mRNA and protein expression levels of miR-34a and PD-L1. No significant differences in miR-34a levels were observed with regard to TP53 status. Forced expression of miR-34a decreased PD-L1 expression, and suppression of miR-34a increased PD-L1 expression. Conclusion: Our present results suggest that miR-34a negatively regulates PD-L1 expression, possibly in a TP53 independent manner in HNSCC.

scholarly journals Management of thyrotoxicosis induced by PD1 or PD-L1 blockade

2021 ◽  
Author(s):  
Alessandro Brancatella ◽  
Isabella Lupi ◽  
Lucia Montanelli ◽  
Debora Ricci ◽  
Nicola Viola ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Checkpoint Inhibitors ◽  
Thyroid Volume ◽  
Clinical Severity ◽  
Response To Treatment ◽  
Thyroid Function Tests ◽  
Thyroid Ultrasound ◽  
Normal Thyroid ◽  
Normal Thyroid Function

Abstract Background Thyrotoxicosis is a common immune-related adverse event in patients treated with PD1 or PD-L1 blockade. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy is lacking, as are data on response to treatment and follow-up. Aim of this study was to better characterize the thyrotoxicosis secondary to immune checkpoint inhibitors, gaining insights into pathogenesis and treatment. Methods We conducted a retrospective study of 20 consecutive patients who had normal thyroid function before starting immunotherapy and then experienced thyrotoxicosis upon PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, 99mTechnecium scintiscan and longitudinal thyroid function tests. Results Five patients had normal scintigraphic uptake (Sci+), no serum antibodies against the TSH receptor and remained hyperthyroid throughout follow-up. The other 15 patients had no scintigraphic uptake (Sci-) and experienced destructive thyrotoxicosis followed by hypothyroidism (N= 9) or euthyroidism (N= 6). Hypothyroidism was more readily seen in those with normal thyroid volume than in those with goiter (P= 0.04). Among Sci- subjects, a larger thyroid volume was associated to a longer time to remission (P<0.05). Methimazole (MMI) was effective only in Sci+ subjects (P<0.05). Conclusion Administration of PD1 or PD-L1 blocking antibodies may induce two different forms of thyrotoxicosis that appear similar in clinical severity at onset: a type 1 characterized by persistent hyperthyroidism that requires treatment with MMI and a type 2 characterized by destructive and transient thyrotoxicosis that evolves to hypo- or euthyroidism. Thyroid scintigraphy and ultrasound help differentiating and managing these two forms of iatrogenic thyrotoxicosis.

scholarly journals Activation of CD8 T cells accelerates anti-PD-1 antibody-induced psoriasis-like dermatitis through IL-6

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ryota Tanaka ◽  
Yuki Ichimura ◽  
Noriko Kubota ◽  
Akimasa Saito ◽  
Yoshiyuki Nakamura ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Cd8 T Cells ◽  
Murine Model ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Inflammation ◽  
Programmed Cell Death 1

Abstract Use of immune checkpoint inhibitors that target programmed cell death-1 (PD-1) can lead to various autoimmune-related adverse events (irAEs) including psoriasis-like dermatitis. Our observations on human samples indicated enhanced epidermal infiltration of CD8 T cells, and the pathogenesis of which appears to be dependent on IL-6 in the PD-1 signal blockade-induced psoriasis-like dermatitis. By using a murine model of imiquimod-induced psoriasis-like dermatitis, we further demonstrated that PD-1 deficiency accelerates skin inflammation with activated cytotoxic CD8 T cells into the epidermis, which engage in pathogenic cross-talk with keratinocytes resulting in production of IL-6. Moreover, genetically modified mice lacking PD-1 expression only on CD8 T cells developed accelerated dermatitis, moreover, blockade of IL-6 signaling by anti-IL-6 receptor antibody could ameliorate the dermatitis. Collectively, PD-1 signal blockade-induced psoriasis-like dermatitis is mediated by PD-1 signaling on CD8 T cells, and furthermore, IL-6 is likely to be a therapeutic target for the dermatitis.

scholarly journals Cancer Immunotherapy Update: FDA-Approved Checkpoint Inhibitors and Companion Diagnostics

2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Julianne D. Twomey ◽  
Baolin Zhang
Keyword(s):  
Cell Death ◽  
Monoclonal Antibodies ◽  
Programmed Cell Death ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Clinical Use ◽  
Companion Diagnostics ◽  
Programmed Cell Death 1

AbstractImmune checkpoint inhibitors (ICIs) are considered a new standard-of-care across many cancer indications. This review provides an update on ICIs approved by the Food and Drug Administration (FDA), with focus on monoclonal antibodies that target the programmed cell death 1 (PD-1) or its ligand, PD-1 ligand 1 (PD-L1), including information on their clinical indications and associated companion diagnostics. The information is further discussed with strategies for identifying predictive biomarkers to guide the clinical use of PD-1/PD-L1-targeted therapies.

284 Real World Data of Sequencing Immune Checkpoint Inhibitors (ICI) after Initial ICI

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A310-A310
Author(s):  
Krishna Gunturu ◽  
Muhammad Awidi ◽  
Rojer Ranjit ◽  
Brendan Connell ◽  
Rachel Carrasquillo ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Clear Understanding ◽  
Real World Data ◽  
World Data

BackgroundICI revolutionized modern Oncology landscape and being utilized in metastatic to adjuvant and neo-adjuvant settings. As Oncologists, we are treating cancer patients with ICI every day, yet there is still a lot that is unknown about these drugs. We don’t have clear understanding of the efficacy and toxicity when sequencing one ICI for another. We conducted a retrospective review of real world data at Lahey Hospital and Medical Center to understand further and to pave path for prospective studies to understand this issue further to improve patient care.MethodsWe retrospectively reviewed Oncology patient charts who received ICI between January1, 2014 to December 18, 2018. Total 483 patients received ICI during this time frame and 22 of these patients received a second ICI either as monotherapy or in combination with other ICI or chemotherapy.ResultsA total of 22 patients received subsequent ICI after the initial ICI as showed in table 1. 15 of the 22 (68%) patients were transitioned from one ICI to another monotherapy. 11 of these patients were transitioned secondary to disease progression (73%), three had immune related adverse events and one was switched per standard of care. One patient had ICI re-challenge. Three patients had a transition from ICI monotherapy to combination ICI therapy. One patient went onto chemo-immunotherapy and 2 patients transitioned from combination ICI to chemo-immunotherapy.Abstract 284 Table 1Real world data of sequencing immune checkpoint inhibitors (ICI) after initial ICIConclusionsICI therapy is evolving and patients are being treated with multiple lines of ICI. In current practices, ICI is frequently being transitioned from cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1) classes or combined with chemotherapy or targeted therapy. It would be prudent to explore the effects of sequencing these medications either as a monotherapy or in combination with other therapies to better serve our patients and to prevent financial toxicity.

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