Oral Presentation ESA-SRB-AOTA 2019

The rising incidence of endocrine toxicity in the era of combination immunotherapy (#245)

Anna Galligan 1 2 , Cherie Chiang 1 3 , Nirupa Sachithanandan 1 4 , Shahneen Sandhu 1 , Richard MacIsaac 4 , Thomas Kay 2 , Bala Krishnamurthy 2
  1. Peter MacCallum Cancer Centre, Melbourne , VIC, Australia
  2. St Vincent's Institute of Medical Research, Melbourne, Australia
  3. Department of Diabetes and Endocrinology, Melbourne Health, Melbourne, VIC, Australia
  4. St Vincent's Hospital, Fitzroy, VIC, Australia

Background: Immune checkpoint blockade is now established as standard of care in several malignancies. Combined cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) blockade results in improved tumour responses in melanoma but is associated with grade 3-4 immune related adverse events (irAEs) in 55% of patients [1].  Immune-mediated damage to endocrine glands can be a diagnostic and management challenge.  We aimed to review the incidence, biochemical evolution and imaging findings of endocrine toxicity related to combined anti CTLA-4 and anti-PD-1 therapy in patients with advanced melanoma.

Methods: A retrospective chart review of patients who received combined ipilimumab and nivolumab for metastatic melanoma at Victorian Comprehensive Cancer Centre (VCCC) between 2016-2019 was undertaken. Onset and duration of abnormal biochemistry in endocrine irAEs were recorded.

Results: 162 patients received combination ipilimumab and nivolumab. At least one irAE was recorded in 135 (83%) of patients, 100 (62%) required glucocorticoids, and 84 (52%) had an unplanned hospital presentation due to irAEs. Thyroiditis occurred in 30.9%, with a median time to onset of 30.9 days (range 1-234 days). 35/50 cases were identified with routine biochemistry performed every 4-6 weeks.TSH receptor antibody was measured in 13 patients and all were negative. 58% of patients with thyroiditis developed permanent hypothyroidism. Cortisol deficiency occurred in 18.5% with a median time to diagnosis of 67.5 days (range 5-286). 4/30 cases of hypophysitis were diagnosed on routine biochemistry while 26/30 cases presented with symptoms prompting investigation.Raised pancreatic enzymes were noted in 6 patients but type 1 diabetes did not occur.

Conclusion: The incidence of thyroiditis and hypophysitis are increasing in the era of combination immunotherapy. Routine thyroid function and cortisol testing leads to the detection of some but not all cases. Early recognition of cortisol deficiency and avoidance of unplanned presentations remains a challenge.

 

  1. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. (2015) 1:23–34. 10.1056/NEJMoa1504030