Inflammation-induced hypoparathyroidism triggered by combination immune checkpoint blockade for melanoma

Journal for Immunotherapy of Cancer
Beckey TrinhHeinz Läubli

Abstract

Treatment with a combination of PD-1 and CTLA-4 targeted checkpoint inhibition has improved outcome of melanoma patients and led to durable remissions but is also associated with significant toxicities. Endocrinopathies such as thyroiditis and hypophysitis are often seen, but other, rarer disturbances have also been described. Endocrinopathies affecting the parathyroid gland are rarely reported and no clear pathomechanism has been proposed. Here, we report a case of severe hypocalcemia due to an antibody-mediated hypoparathyroidism as an immune-related adverse event (irAE) in a patient who was treated with the anti-PD-1 antibody nivolumab and anti-CTLA-4 antibody ipilimumab. Hypocalcemia was rapidly corrected by substitution, but the endogenous serum parathyroid hormone (PTH) remained low. The patient demonstrated a rapid and profound tumor response to the combination immune checkpoint blockade, but developed a severe colitis that required high-dose intravenous corticosteroid and anti-TNFα therapy. During this strong immunosuppression the PTH level normalized and the calcium levels were stable without substitution. However, during tapering of immunosuppressants, the PTH and calcium levels decreased again to a level requiring ca...Continue Reading

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Citations

Mar 1, 2020·The Journal of Clinical Endocrinology and Metabolism·Isabella LupiClaudio Marcocci
Jul 3, 2020·Journal of Clinical Medicine·Naoko OkuraKoichi Takayama
Jun 27, 2020·International Journal of Endocrinology·Swarna Sri NalluruNitin Trivedi
Aug 31, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Luca IamartinoEnikö Kallay
Jan 22, 2021·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Rena PollackTzahi Neuman
Mar 26, 2021·Clinical Medicine : Journal of the Royal College of Physicians of London·Rosie HattersleyAndrew J Lansdown
Apr 21, 2021·Nature Reviews. Endocrinology·Jordan J WrightDouglas B Johnson
Dec 29, 2020·Mayo Clinic Proceedings. Innovations, Quality & Outcomes·Omar M El KawkgiRobert A Wermers

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Methods Mentioned

BETA
biopsies

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