Immune checkpoint inhibitors, endocrine adverse events, and outcomes of melanoma

Abstract

Objective: Immune checkpoint inhibitors (ICI) can cause endocrine adverse events. However, endocrine AEs could be related to better treatment outcomes. Our aim was to investigate whether this holds true in a real-world setting of metastatic melanoma patients. Design: A retrospective single-institution study. Methods: We included 140 consecutive metastatic melanoma patients treated with ICI between January 2012 and May 2019. We assessed endocrine toxicity and best possible treatment outcomes from electronic patient records, including laboratory parameters, and radiological images. Results: Of the treated patients, 21 patients (15%) were treated with ipilimumab, 46 (33%) with nivolumab, 67 (48%) with pembrolizumab, and six (4%) with combination therapy (ipilimumab + nivolumab). Endocrine AEs appeared in 29% (41/140) patients. Three patients had two different endocrine AEs. Thyroid disorders were the most common: 26% (36/140), followed by hypophysitis: 4% (5/140). Three subjects (2%, 3/140) were diagnosed with autoimmune diabetes. Three patients had to terminate treatment due to endocrine toxicity. Radiological manifestations of endocrine AEs were found in 16 patients (39%, 16/41). Endocrine toxicity was associated with significantly better treatment outcomes. Median progression-free survival (8.1 months, range 5.1 – 11.1 months vs. 2.7 months, range 2.4 – 3.0 months, P < 0.001), and median overall survival (47.5 months, range 15.5 – 79.5 months vs. 23.7 months, range 15.3 – 32.1 months, P = 0.035) were longer for patients experiencing endocrine AEs. Conclusions: The higher number of endocrine AEs suggest regular laboratory monitoring aids in AE detection. Endocrine AEs in metastatic melanoma may correlate with better treatment outcomes.

Patients with melanoma treated with immune checkpoint inhibitors who had non-thyroid endocrine and skin immune-related adverse events have better prognosis: A systematic review and meta-analysis

“…Of the included studies, 46 were retrospective ( 13 – 17 , 32 , 34 , 35 , 39 , 41 , 43 – 52 , 54 , 55 , 57 , 59 – 72 , 74 – 78 , 82 – 85 ), 13 were prospective ( 18 , 33 , 36 – 38 , 40 , 53 , 56 , 58 , 73 , 79 – 81 ) (including four studies that extracted data from clinical trials ( 18 , 33 , 73 , 79 )), and one included both retrospective and prospective data ( 42 ). All included studies assessed the relationship between the presence of irAEs and prognosis (12 of them examined the effect of irAE grades ( 14 , 37 , 45 , 57 , 58 , 68 , 71 , 73 , 76 , 82 , 84 , 85 )), 18 studies assessed endocrine irAEs (any, thyroiditis, or hypophysitis) ( 32 , 34 , 44 , 46 – 48 , 51 , 55 , 56 , 60 , 68 – 70 , 73 , 76 , 78 , 81 , 85 ), five assessed pulmonary irAEs ( 32 , 34 , 46 ...…”

“…All included studies assessed the relationship between the presence of irAEs and prognosis (12 of them examined the effect of irAE grades ( 14 , 37 , 45 , 57 , 58 , 68 , 71 , 73 , 76 , 82 , 84 , 85 )), 18 studies assessed endocrine irAEs (any, thyroiditis, or hypophysitis) ( 32 , 34 , 44 , 46 – 48 , 51 , 55 , 56 , 60 , 68 – 70 , 73 , 76 , 78 , 81 , 85 ), five assessed pulmonary irAEs ( 32 , 34 , 46 , 56 , 76 ), 21 assessed skin irAEs (any, rash, or vitiligo) ( 32 , 34 , 38 , 40 , 42 , 46 – 48 , 51 , 53 , 54 , 56 , 62 – 64 , 73 , 74 , 76 , 79 , 81 , 85 ), nine assessed gastrointestinal irAEs (any, colitis, or diarrhea) ( 32 , 34 , 46 , 56 , 58 , 73 , 76 , 77 , 85 ), and five assessed hepatic irAEs ( 32 , 34 , 36 , 76 , 85 …”

“…A total of 57 studies included OS data ( 13 – 18 , 32 – 39 , 41 – 58 , 60 – 71 , 73 – 85 ) and 34 included PFS data ( 14 , 15 , 18 , 32 , 33 , 36 – 42 , 47 , 49 , 54 , 55 , 58 – 60 , 62 , 64 , 66 , 68 – 72 , 75 , 76 , 78 , 79 , 81 , 82 , 85 ). Geographically, 18 studies were from Asian countries ( 35 , 39 , 48 , 56 , 61 – 66 , 69 , 76 – 81 , 85 ), 24 from European countries ( 13 – 16 , 33 , 36 – 38 , 41 – 43 , 45 , 47 , 50 , 53 – 55 , 58 , 59 , 68 , 74 , 75 , 82 , 84 ), six from the United States ( 32 , 44 , 46 , 52 , 67 , 70 ...…”

“…A total of 57 articles assessed the association between the occurrence of irAEs and OS in patients with melanoma ( 13 – 18 , 32 – 39 , 41 – 58 , 60 – 71 , 73 – 75 , 77 – 86 ), and 34 assessed PFS ( 14 , 15 , 18 , 32 , 34 , 36 – 42 , 47 , 49 , 54 , 55 , 58 – 60 , 62 , 64 , 66 , 68 – 72 , 75 , 76 , 78 , 79 , 81 , 82 , 85 ). Among these, the study of Abu-Sbeih et al.…”

Translating the immune microenvironment of thyroid cancer into clinical practice

“…Most are manageable (grade I or II) and rarely require drug discontinuation. These adverse effects were thoroughly detailed by Karhapää et al in a recent publication (Karhapää et al 2022).…”