Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy

Abstract

Background:Recent phase III clinical trials have established the superiority of the anti-PD-1 antibodies pembrolizumab and nivolumab over the anti-CTLA-4 antibody ipilimumab in the first-line treatment of patients with advanced melanoma. Ipilimumab will be considered for second-line treatment after the failure of anti-PD-1 therapy.Methods:We retrospectively identified a cohort of 40 patients with metastatic melanoma who received single-agent anti-PD-1 therapy with pembrolizumab or nivolumab and were treated on progression with ipilimumab at a dose of 3 mg kg−1 for a maximum of four doses.Results:Ten percent of patients achieved an objective response to ipilimumab, and an additional 8% experienced prolonged (>6 months) stable disease. Thirty-five percent of patients developed grade 3–5 immune-related toxicity associated with ipilimumab therapy. The most common high-grade immune-related toxicity was diarrhoea. Three patients (7%) developed grade 3–5 pneumonitis leading to death in one patient.Conclusions:Ipilimumab therapy can induce responses in patients who fail the anti-PD-1 therapy with response rates comparable to previous reports. There appears to be an increased frequency of high-grade immune-related adverse events including pneumonitis that warrants close surveillance.

The next‐generation BET inhibitor, PLX51107, delays melanoma growth in a CD8‐mediated manner

“…Developing second‐line therapies is key as the treatment options for these patients are ineffective. For example, melanoma patients treated with anti‐CTLA‐4 as a second‐line therapy for anti‐PD‐1 non‐responsive disease have poor response rates (Aya et al, ; Bowyer et al, ; Jacobsoone‐Ulrich et al, ; Zimmer et al, ). We showed that PLX51107 profoundly reduced the growth of mouse melanomas in vivo that were non‐responsive to anti‐PD‐1 treatment.…”

Investigation of clinical factors associated with longer overall survival in advanced melanoma patients treated with sequential ipilimumab

“…We administrated ipilimumab to patients who showed disease progression while being treated with an anti‐PD‐1 antibody. In past reports, the objective response rates were 3.6–16% in advanced melanoma patients given an anti‐PD‐1 antibody followed by ipilimumab . However, ipilimumab therapy is reportedly used more frequently and produces more severe immune‐related adverse events (irAE) than nivolumab .…”

Thyrotoxicosis and Adrenocortical Hormone Deficiency During Immune-checkpoint Inhibitor Treatment for Malignant Melanoma

“…In our case, upon activation of antiTg and possibly anti-ACTH immunity with cross presentation of melanoma antigen, exacerbation of thyroiditis and deterioration of ACTH secretion might be seen. Bowyer et al reported that in 35% of patients with melanoma who received anti-CTLA-4 antibody after discontinuation of anti-PD-1 antibody, grade 3-4 irAEs were developed (16). They report clinical benefits of a sequential administration of nivolumab followed by ipilimumab in patients with advanced melanoma, albeit associated with a higher frequency of adverse events.…”