Endocrine Abstracts

Background: PD-L1 represents a novel class of drugs for treatment of a broad spectrum of malignancies including onco-hematologic diseases. This treatment is associated with several immuno-related adverse events (irAEs). Thyroid diseases and diabetes are among the most common PD-L1 endocrine-irAEs reported in solid cancers.

Aims: To describe the frequency, the onset and the characteristics of PD-L1 endocrine-irAEs in patients with hematologic malignancies.

Materials and methods: We retrospectively collected data of 62 patients with lymphoma, attending the Institute of Hematology Seràgnoli of Bologna between June 2014 and August 2018, treated with PD-L1 (Nivolumab or Pembrolizumab) according to the Authority-approved doses and administration. All patients underwent metabolic and hormonal exams before the initiation of PD-L1 and during follow-up.

Results: Of 62 patients (median age: 29 years, range: 16–68), 18 affected by Nodular Sclerosis Hodgkin Lymphoma (NSHL) were treated with Nivolumab, 26 and 18 affected by NSHL and Primary Mediastinal B-cell Lymphoma, (PMBCL) respectively were treated with Pembrolizumab. All patients were followed for a median of 112 weeks (range: 4–270). The total frequency of PD-L1 endocrine-irAEs was 8.1%, characterized by only thyroid diseases. Four (2 NSHL and 1 PMBCL on Pembrolizumab, and 1 NSHL on Nivolumab) developed sudden-onset hypothyroidism at different times (from 16 to 44 weeks after PD-L1 starting). One NSHL on Pembrolizumab had an initial thyrotoxicosis at 6 weeks turning to overt hypothyroidism after 9 weeks. All 5 subjects were asymptomatic. Two of them had positive anti-thyroid autoantibodies (anti-thyroid peroxidase and anti-thyroglobulin), whereas none had detectable anti-TSH receptors. All hypothyroid subjects started l-tyroxine therapy. None of the patients developed diabetes. At the last follow up, of the 5 patients with endocrine-irAE, 3 showed complete remission and 2 disease progression of the lymphoma. No correlations were found between the endocrine-irAEs and previous oncologic therapies (P = 0.081), and tumour outcomes (P = 0.278 for best response to Pembrolizumab; P = 0.921 for the last response to Pembrolizumab; P = 0.278 for deaths).

Conclusion: The frequency of PD-L1 endocrine-irAEs in this cohort of hematologic malignancies was lower than those reported for solid cancers, and only characterized by thyroid disease. Unexpectedly, no case of PD-L1 inducing diabetes mellitus was shown. As for solid tumours the onset of endocrine-irAES was extremely variable and no correlation with tumour outcome was found.