Size matters: Early progression of melanoma brain metastases after treatment with immune checkpoint inhibitors

Background. Immune checkpoint inhibitors (ICIs) are effective treatments for patients with metastatic melanoma, including patients with brain metastasis (BM). However, half of patients with melanoma BM have intracranial progression within 6 months after the start of ICIs. We investigated whether size affects response to ICIs in patients with melanoma BM. Methods. In this single-center cohort study, patients with melanoma BM who were treated with ICIs between 2012 and 2021 were included. Clinical and radiologic features were collected at baseline. Longest axial diameter of all BMs was measured on baseline and follow-up MRI, and segmentation was performed for all BMs on baseline MRI. Lesion-level logistic regression analysis and patient-level survival analysis were performed for early BM progression (ie, within 6 months after start of ICIs) and intracranial progression-free survival (PFS), respectively. Results. A total of 82 patients were included with a total of 464 BMs. At baseline, 37.8% of patients had >= 4 BMs and 53.7% of patients had at least one BM with a diameter >= 10 mm. In multivariable analysis on the lesion level, baseline BM diameter was associated with early BM progression (odds ratio 1.10, 95%CI 1.05-1.15, P < .001). On the patient level, having at least one BM >= 10mm was associated with shorter intracranial PFS (hazard ratio 2.08, 95%CI 1.64-5.56, P < .001). Conclusions. Large BM diameter was associated with a higher risk of early progression after the start of ICIs. Therefore, local therapy should be considered for patients who are treated with ICIs and who have melanoma BMs >= 10 mm.