Richard Joseph, MD, is an assistant professor of medicine/oncology at Mayo Clinic. His Hematology/Oncology fellowship was completed at MD Anderson Cancer Center. He is a voting member of the NCCN (National Comprehensive Cancer Network. He belongs to Melanoma International’s Scientific Advisory Board and received MIF’s Doctor of the Year award for 2015.
» PIGMENT CHANGES WITH COMBINATION THERAPIES
I’ve read that Yervoy can cause pigment changes in skin and some patients develop white eyebrows and then white hair. It appears as a good sign to those patients that drug is working. Since the combo came out of nivo/ipi, do we know of any patients who have been experiencing any of these signs as well? I recently completed the four combo doses and recently noticed a tuft of white hair growing out from my scalp near my scar where melanoma can still be seen in the surrounding soft tissue.
Dr. Joseph: “The whitening of skin and hair is caused vitiligo and is caused by the immune destruction of pigmented cells. Vitiligo is relatively common with both ipilimumab, pembrolizumab, and nivolumab as well as the combination of ipilimumab and nivolumab. In general, we consider vitiligo to be a good sign that the immune system is recognizing and attacking pigmented cells.”
» RESPONSE RATES FOR VARIOUS TYPES OF MELANOMA
Now that the immunotherapies have been deployed for sometime, are there any differences in the response rates using them for mucosal, ocular, or other types of melanoma?
Dr. Joseph: “In 2015, Larkin et al presented at Society of Melanoma Research an update of the efficacy of immunotherapy for mucosal melanoma. In this presentation, the general take home point was that immunotherapy is effective in mucosal melanoma but at what appears to be half the rate of cutaneous melanoma. At ASCO 2016, Tsai et al presented a retrospective analysis on the efficacy of single agent anti-PD1 in patients with ocular melanoma. In this study, anti-PD1 agents generated a response in only 2-3% of patients. This echoes my experience as well. There is not enough data to comment on the efficacy of ipilimumab/nivolumab in patients with ocular melanoma and in fact there are on-going trials now to assess the efficacy.”
» STAGE IIC & III
What’s the latest for the stage IIC and stage III patients in terms of adjuvant therapies, as some data should start showing up now?
Dr. Joseph: “Unfortunately, data on the adjuvant studies takes longer to develop because the endpoints are much longer than in patients with unresectable disease. ECOG 1609 which compared adjuvant ipilimumab 3 mg/kg, adjuvant ipilimumab 10 mg/kg, and adjuvant interferon finished enrolling and recruiting patients in late 2014. I would expect that the results will not be ready until 2017 at the earliest. A study comparing adjuvant nivolumab to ipilimumab also has finished enrolling in 2015 but results from this trial would also be expected to take 3-4 years.”
»BRAF/MEK vs. Immunotherapy
Switching from BRAF+MEK to immunotherapy or is the new immunotherapty combo the first line to start with?
Dr. Joseph: “I personally do not believe there will be “one best regimen” for all patients. There are so many variables that go into deciding what treatment to start patients on including BRAF status, health of the patient, tumor burden, LDH levels, and willingness of patient to tolerate symptoms and risk. There is a trial underway testing front line BRAF/MEK versus upfront ipilimumab/nivolumab. This study will help to answer the question of what’s “best” to start.”
What is the best dose of ipi when combined with anti pd1?
Dr. Joseph: “In patients with melanoma, currently there is only one FDA approved dose of ipilimumab to combine with anti-PD1 and that’s 3 mg/kg. There is a study looking at lower dose of ipilimumab at 1 mg/kg which was tested more extensively in patients with renal cell carcinoma. We know from the data in renal cell, that the ipilimumab 1 mg/kg dose is much less toxic but we do not know the efficacy at this point.”
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