Endocrine Abstracts

Background: Immune checkpoint inhibitors (ICIs) constitutes a novel treatment for patients with melanoma. Endocrine-related adverse effects are now a distinctive clinical entity of ICIs, with hypophysitis and thyroiditis being the most common. Recent consensus doesn’t suggest routinely screening of bone mass indexes in patients on ICIs since data in the literature are scarce.

Methods: Data regarding bone disease were retrospectively analysed in 118 patients with melanoma treated with ICIs who were referred to our unit for endocrine-related adverse events. Only patients with available data of bone density in two sites (left femoral bone and lumbar spine), as defined by Dual energy X-ray absorptiometry (DXA) before as well as after ICIs treatment were included in the study. Biochemical markers associated to bone remodelling such as calcium, phosphorus, alkaline phosphate, 25-OH vitamin D and parathormone levels were also registrated. Ten-year probability of fracture score (FRAX score) adapted to Greek population was also calculated. DXA was assessed at least one year post-ICIs interruption (median follow up: 2.5 years).

Results: Six patients (all females, median age: 70.5 years) fulfilled the criteria of inclusion in this case series. Five patients had been treated with systemic monotherapy with an anti-PD1 agent (nivolumab (n=4) or pembrolizumab (n=1)). The last patient had received combination therapy with anti-PD1 plus anti-CTLA4 (nivolumab plus ipilimumab) therapy. At baseline before any treatment, 2 (33.3%) patients presented with normal bone density, 3(50%) with osteopenia and the last one (16.6%) with osteoporosis treated with calcium replacement and bisphosphonates (ibandronic acid). Baseline levels of biochemical bone metabolism markers were within the normal range except for 25 OH vitamin D levels which was deficient in all 6 patients necessitating the initiation of replacement with cholecalciferol with a median dose of 2000 units administered daily. No bone fracture was diagnosed radiologically during ICIs treatment. None of the patients presented any difference in the T score, the BMD or the FRAX score during the follow-up post- ICIs treatment.

Conclusions: Bone disorders are rarely searched in patients treated with ICIs thus data in the literature are rare. Our case series analysis showed no difference of T score, BMD levels or of the FRAX score in 6 patients with melanoma before and after receiving ICIs in a median follow up of 2.5 years. No osteoporotic fracture was detected neither. Further large-scale analyses with longer follow-up are required in order to assess the effect of ICIs on bone metabolism.