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PD-L1 inhibitor-associated thyroiditis: a retrospective review at Mayo Clinic


Programmed cell death protein ligand-1 ( PD-L1 ) inhibitors are novel anti-cancer therapies but are associated with potentially therapy limiting immune-related adverse effects ( IRAEs ).

The purpose of the study was to characterize thyroid-related IRAEs in order to improve case detection and overall patient management.

A retrospective cohort study of cancer patients receiving PDL-1 inhibitors between 6/1/2016 – 1/30/2018 at the Mayo Clinic, was conducted.
Clinico-pathologic and laboratory data, including overall survival ( OS ) was collected.
Of 91 patients treated with PDL-1 inhibitors ( median age 68 years, 52% male ) with a median follow up of 5 ( IQR 2 – 9 ) months, 42 ( 46% ) developed an IRAE, including 23 ( 25% ) thyroid IRAEs ( 22 from Atezolizumab, 1 from Avelumab ).
The median time to thyroid IRAEs was 1.4 months or after 2 doses of PDL-1 inhibitor.

Acute thyroiditis occurred in 5 ( 22% ), of which 3 progressed to hypothyroidism.
New onset hypothyroidism occurred in 14 ( 61% ) patients, 4 overt and 10 subclinical, of which 2 resolved.
Worsening hypothyroidism occurred in 4 ( 17% ).

Management included observation in 52% and Levothyroxine in 48%.

Thyroperoxidase ( TPO ) antibodies were elevated in 4/13 ( 31% ) at baseline, of which 2 developed thyroid IRAE.
TPO antibodies were elevated in 4/18 ( 22% ) at the time of thyroiditis / hypothyroidism ( median titer 220 IU/mL ).

Diffusely elevated fluorodeoxyglucose ( FDG ) thyroid uptake on positron emission tomography ( PET ) scan was present in 6/24 of which 5 developed thyroid IRAE ( p = 0.001 ).

The mean overall survival since start of PDL-1 inhibitor therapy was 9.2 months, and on subgroup analysis, was 12 months in patients with thyroid IRAE versus 9.9 months without ( p = 0.03 ).

Thyroiditis, presenting as acute thyrotoxicosis progressing to hypothyroidism or as new onset hypothyroidism, is the most common endocrine IRAE following PDL-1 inhibitor therapy and has comparable and/or higher incidence than with other immune checkpoint inhibitors.

Diffuse thyroid uptake on FDG-PET scan but not elevated TPO antibodies appears to identify patients at risk for thyroiditis / hypothyroidism.
Whether patients developing thyroiditis, or other IRAEs, may be a biomarker of anti-tumor immune response and improved overall survival requires additional study. ( Xagena )

Source: Kotwal A et al, Annual Meeting of American Thyroid Association ( ATA ), 2018

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