Response to ipi AFTER being treated with anti-PD1

Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy.  Bowyer, Prithviraj, Lorigan, et al.   Br J Cancer. 2016 Apr 28.

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.

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 for a maximum of four doses.

Ten percent of patients achieved an objective response to ipilimumab, and an additional 8% experienced prolonged (more than 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.  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.

Update on immunology studies by Dr. Weber

CheckMate 064 - Sequential nivo then ipi (ORR of 41%), ipi then nivo (ORR of 20%)

Pembro response rate generally and after ipi

For what it's worth.....c