On 2014 Sep 27, David Keller commented:

Pembrolizumab first-line for metastatic melanoma & preexisting autoimmune disease?

Patients with preexisting autoimmune diseases were excluded from the landmark trials of ipilimumab and pembrolizumab, which therefore cannot provide high-quality safety data for these patients. The grade 4 (life-threatening) and grade 5 (fatal) adverse events for both medications were primarily autoimmune in nature, in trial patients with no history of autoimmune disease. Pembrolizumab appears to have a somewhat lower rate of severe-to-fatal adverse events than ipilimumab, although no head-to-head comparison is available.

Pembrolizumab was recently approved by the FDA for treating metastatic melanoma patients who have disease progression following ipilimumab. Medicare and private insurers are quite strict about not paying for off-label use of pembrolizumab, even for patients with active autoimmune disease. I have personally corresponded with two authors of this paper who advocate first-line treatment using pembrolizumab in selected clinical scenarios, for enhanced patient safety. Although there is controversy on this question in the immuno-oncology community, it seems reasonable to let treating oncologists decide when pembrolizumab should be used first-line and off-label for selected high-risk patients, pending their inclusion in randomized trials. As matters now stand, the wealthy who can pay cash for pembrolizumab effectively have access to a treatment option not available to less-wealthy melanoma patients. The FDA should reconsider their narrow prescribing indication for pembrolizumab, the adverse effects this may have on melanoma patients with preexisting autoimmune diseases, and the disparity caused by expensive off-label treatment options which are available only to patients who can pay the very large cash price in advance.

On 2014 Sep 27, David Keller commented:

Pembrolizumab first-line for metastatic melanoma & preexisting autoimmune disease?

Patients with preexisting autoimmune diseases were excluded from the landmark trials of ipilimumab and pembrolizumab, which therefore cannot provide high-quality safety data for these patients. The grade 4 (life-threatening) and grade 5 (fatal) adverse events for both medications were primarily autoimmune in nature, in trial patients with no history of autoimmune disease. Pembrolizumab appears to have a somewhat lower rate of severe-to-fatal adverse events than ipilimumab, although no head-to-head comparison is available.

Pembrolizumab was recently approved by the FDA for treating metastatic melanoma patients who have disease progression following ipilimumab. Medicare and private insurers are quite strict about not paying for off-label use of pembrolizumab, even for patients with active autoimmune disease. I have personally corresponded with two authors of this paper who advocate first-line treatment using pembrolizumab in selected clinical scenarios, for enhanced patient safety. Although there is controversy on this question in the immuno-oncology community, it seems reasonable to let treating oncologists decide when pembrolizumab should be used first-line and off-label for selected high-risk patients, pending their inclusion in randomized trials. As matters now stand, the wealthy who can pay cash for pembrolizumab effectively have access to a treatment option not available to less-wealthy melanoma patients. The FDA should reconsider their narrow prescribing indication for pembrolizumab, the adverse effects this may have on melanoma patients with preexisting autoimmune diseases, and the disparity caused by expensive off-label treatment options which are available only to patients who can pay the very large cash price in advance.