On 2014 Nov 19, David Keller commented:

A landmark paper with important implications for melanoma patients

The results obtained by combining high-dose ipilimumab (10 mg/kg) with GM-CSF (sargramostim) are remarkable. The combination increased median overall survival by 4.8 months compared with high-dose ipilimumab alone, an increase of over 37%, and the combination also reduced the rate of serious adverse events significantly compared with high-dose ipilimumab monotherapy. Patients with advanced melanoma and poor response to existing treatments will want to discuss these results with their oncologists, particularly since GM-CSF is currently available in the U.S.

Since GM-CSF is already approved for other indications, there will be great pressure on oncologists to prescribe ipilimumab in combination with GM-CSF on the basis of this study, particularly for patients whose tumor burden worsens despite approved therapy. Questions which will be encountered include:

1) Would the pairing of GM-CSF with the approved dose of ipilimumab (3 mg/kg) have similar benefits, despite the fact that the ipilimumab dose used in the study was more than 3 times larger than the approved dose?

2) Given the reduction in toxicity of the combination compared with ipilimumab monotherapy, can the approved dose of ipilimumab be safely tripled to 10 mg/kg if used in combination with GM-CSF?

3) Is there any reason to believe that PD-1 checkpoint inhibitors, such as pembrolizumab, given in combination with GM-CSF, would not afford similar improvements in survival and adverse events?

Patients with advanced melanoma who do not respond to currently approved treatments have little to lose. There is no reason to force these patients to wait for the results of confirmatory studies which they may have little hope of surviving to see published. Those that can be accommodated into clinical trials should be encouraged to participate, while the others should be offered the option of adding GM-CSF to their checkpoint inhibitor, if the latter fails to control their disease.

On 2014 Nov 19, David Keller commented:

A landmark paper with important implications for melanoma patients

The results obtained by combining high-dose ipilimumab (10 mg/kg) with GM-CSF (sargramostim) are remarkable. The combination increased median overall survival by 4.8 months compared with high-dose ipilimumab alone, an increase of over 37%, and the combination also reduced the rate of serious adverse events significantly compared with high-dose ipilimumab monotherapy. Patients with advanced melanoma and poor response to existing treatments will want to discuss these results with their oncologists, particularly since GM-CSF is currently available in the U.S.

Since GM-CSF is already approved for other indications, there will be great pressure on oncologists to prescribe ipilimumab in combination with GM-CSF on the basis of this study, particularly for patients whose tumor burden worsens despite approved therapy. Questions which will be encountered include:

1) Would the pairing of GM-CSF with the approved dose of ipilimumab (3 mg/kg) have similar benefits, despite the fact that the ipilimumab dose used in the study was more than 3 times larger than the approved dose?

2) Given the reduction in toxicity of the combination compared with ipilimumab monotherapy, can the approved dose of ipilimumab be safely tripled to 10 mg/kg if used in combination with GM-CSF?

3) Is there any reason to believe that PD-1 checkpoint inhibitors, such as pembrolizumab, given in combination with GM-CSF, would not afford similar improvements in survival and adverse events?

Patients with advanced melanoma who do not respond to currently approved treatments have little to lose. There is no reason to force these patients to wait for the results of confirmatory studies which they may have little hope of surviving to see published. Those that can be accommodated into clinical trials should be encouraged to participate, while the others should be offered the option of adding GM-CSF to their checkpoint inhibitor, if the latter fails to control their disease.