Combined PD-1 and CTLA-4 Blockade Increases the Risks of Multiple Pituitary Hormone Deficiency and Isolated Adrenocorticotropic Deficiency: A Prospective Study.
Patients receiving PD-1/CTLA-4 antibody therapy have a significantly higher risk of multiple pituitary hormone deficiencies compared to those on PD-1 monotherapy.
Where it sits
this study against the rest of the ghrp-2 (pralmorelin) corpusSummary and findings
This study evaluated the incidence of multiple pituitary hormone deficiency (Multi-D) and isolated adrenocorticotropic hormone deficiency (IAD) in patients treated with PD-1/CTLA-4 antibodies compared to PD-1 antibody monotherapy. A total of 74 patients received PD-1/CTLA-4 antibodies, while 748 received PD-1 antibodies. The study found significantly higher rates of pituitary immune-related adverse events in the combination therapy group.
Abstract
Backgruound Anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) monotherapy induces two types of pituitary immunerelated adverse events (irAEs): multiple pituitary hormone deficiency (Multi-D; impairment of ≥2 anterior pituitary hormones) and isolated adrenocorticotropic hormone (ACTH) deficiency (IAD). Combination therapy with CTLA-4-Ab and anti-programmed cell death-1 antibody (PD-1/CTLA-4-Abs), which is increasingly replacing CTLA-4-Ab monotherapy, frequently causes pituitary irAEs; however, whether it increases Multi-D/IAD incidence is unknown. Methods In total, 74 and 748 patients with malignancies treated with PD-1/CTLA-4-Abs and PD-1-Ab, respectively, were prospectively evaluated for ACTH and cortisol levels at baseline and every 6 weeks after treatment initiation, and then observed until the last clinical visit. The characteristics of pituitary irAEs were evaluated by pituitary stimulation tests and compared with those induced by PD-1-Ab monotherapy. Results PD-1/CTLA-4-Abs therapy showed higher incidence rates of pituitary irAEs (16/74 [21.6%] vs. 25/748 [3.3%], P<0.001), Multi-D (9/74 [12.2%] vs. 2/748 [0.3%], P<0.001), and IAD (7/74 [9.5%] vs. 23/748 [3.1%], P=0.014) than PD-1-Ab monotherapy. ACTH deficiency was observed in all cases, whereas the prevalence rates of luteinizing hormone deficiency (8/16 [50.0%] vs. 1/25 [4.0%]), follicle-stimulating hormone deficiency (6/16 [37.5%] vs. 1/25 [4.0%]), and thyrotropin deficiency (4/16 [25.0%] vs. 0/25 [0%]) were significantly higher after PD-1/CTLA-4-Abs than after PD-1-Ab treatment. Pituitary enlargement, which was observed only in the Multi-D cases, was significantly more frequent after PD-1/CTLA-4-Abs than after PD-1-Ab treatment (6/16 [37.5%] vs. 0/25 [0%], P=0.002). Conclusion This prospective study revealed high risks of both Multi-D and IAD under PD-1/CTLA-4-Abs treatment, emphasizing the need for careful evaluation of pituitary function.
Background
The paper addresses the clinical question of whether combined PD-1 and CTLA-4 blockade increases the risk of pituitary hormone deficiencies. Prior studies have suggested immune checkpoint inhibitors can affect endocrine function, but the extent and mechanisms remain unclear. This study is significant as it aims to provide prospective data on this potential adverse effect.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Key findings
- Not reported in abstract.
Limitations
- Not reported in abstract.