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. 2016 May 10;114(10):1084-9.
doi: 10.1038/bjc.2016.107. Epub 2016 Apr 28.

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

S Bowyer  1   2 , P Prithviraj  3   4 , P Lorigan  5 , J Larkin  6 , G McArthur  7 , V Atkinson  8 , M Millward  2   9 , M Khou  10 , S Diem  6 , S Ramanujam  11 , B Kong  10 , E Liniker  11 , A Guminski  11 , P Parente  12 , M C Andrews  3   4 , S Parakh  3 , J Cebon  3   4 , G V Long  11   13 , M S Carlino  10   11   13 , O Klein  3   4
Affiliations

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

S Bowyer et al. Br J Cancer. .

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.

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Conflict of interest statement

P Lorigan received consultancy and honoraria from Bristol Myer Squibb, Glaxosmithkline, Amgen, Novartis, Roche, Merck. J Larkin received institutional research support from MSD, Bristol Myer Squibb, Pfizer and Novartis; non-remunerated consultancy for Glaxosmithkline, Novartis, MSD, Bristol Myer Squibb, Pfizer and Roche/Genentech. G McArthur received research grant support from Pfizer, Celgene, Ventana; consultancy for Provectus; uncompensated consultancy for Pfizer, Millenium, Glaxosmithkline, Roche/Genentech, Novartis, Bristol Myer Squibb and Amgen. V Atkinson participated in an advisory committee for MSD; was a member of the advisory board for Bristol Myer Squibb; received honoraria from GSK and received travel support from GSK, BMS and Roche. M Millward received consultancy or advisory role to Roche, Bristol Myer Squibb, MSD and Glaxosmithkline; received research funding from Roche and Glaxosmithkline. S Ramanujam received travel and accommodation grants from Amgen. MC Andrews received travel support from Bristol Myer Squibb and MSD. J Cebon participated in advisory boards for Amgen and Merck. GV Long participated in advisory boards of Amgen, Bristol Myer Squibb, Glaxosmithkline, Novartis, Provectus, Roche and Merck Inc. MS Carlino participated in advisory boards for Merck, Amgen, Novartis and Bristol Myer Squibb. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Computer tomography scans demonstrating a severe pneumonitis during ipilimumab therapy; a 61-year-old patient with metastatic melanoma commenced ipilimumab after having progressed several weeks earlier on nivolumab treatment (A). She developed a severe pneumonitis after three doses of ipilimumab (B) that resolved on intensified immunosuppression with a prolonged course of high dose intravenous and oral glucocorticoids (C).
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