Melanoma

A study found that melanoma is more common in immunosuppressed patients, including patients with prior solid organ transplant, patients with lymphoma, and patients with HIV/AIDS.

Two-Drug Combo May Delay Melanoma Progression

Combinationtreatment with the kinase inhibitor drugs dabrafenib and trametinib appears to postpone the development of drug resistance in patients with BRAFpositive metastatic melanoma, according to a new study by Keith Flaherty, MD, of the Massachusetts General Hospital Cancer Center, and colleagues. The report was published in the New England Journal of Medicine and presented at the European Society for Medical Oncology meeting in Vienna. The study was conducted at 14 sites in the United States and Australia, and included 162 patients who received different dose combinations of the drugs: 2 daily 150-mg doses of dabrafenib plus one 2-mg dose of trametinib; the same dabrafenib dose with a 1-mg dose of trametinib; or dabrafenib alone.

In about half of patients with metastatic melanoma, tumor growth is caused by genetic mutations that keep the BRAF protein (part of the mitogen-activated protein kinase [MAPK] growth-factor cell growth pathway) constantly activated. Medications that can inhibit BRAF activity can stop and reverse tumor growth in approximately 90% of patients. The response is temporary, however, and tumor growth resumes in 6 to 7 months. Drug resistance develops because the MAPK pathway gets reactivated through activation of MEK—another MAPK pathway protein. The dabrafenib/ trametinib combination was studied because research suggested that adding the MEK inhibitor (trametinib) to the BRAF inhibitor (dabrafenib) delays the emergence of resistance.

Treatment with both combinations of dabrafenib and trametinib allowed a 4-monthlonger delay in drug resistance than treatment with dabrafenib alone. After 1 year, 41% of patients receiving the full-dose combination treatment had no melanoma progression compared with 9% of those receiving dabrafenib alone.

Even Without Sun Exposure, Redheads May Be More Susceptible to Melanoma

A new study published in Nature (online, October 31, 2012) finds that in mice with red fur there is a genetic mutation that raises the risk of melanoma, even without exposure to sun.

Researchers manipulated the genetic makeup of mice to give them a mutant form of a gene that raises the risk of melanoma, and though none of the mice were exposed to any ultraviolet radiation, they were much more likely to develop melanoma. About 10% of the mice without red fur developed melanoma; at least 50% of the red-furred mice with the genetic mutation developed melanoma, and in a shorter amount of time than those without red fur. In addition, researchers found that albino mice with the genetic mutation didn’t develop melanoma, suggesting that the pigmentation of red fur in mice makes them more susceptible to melanoma if they have a genetic mutation.

Study coauthor David Fisher, MD, PhD, of the Cutaneous Biology Research Center at Massachusetts General Hospital, hypothesized that the increased risk of melanoma in red mice that had the genetic mutation but didn’t get sun exposure is related to how the body creates pigmentation. The process may raise the risk of melanoma. If the finding is confirmed in humans, it would suggest that for people with red hair and fair skin color, being careful about sun exposure and using sunscreen may not be sufficient; they have to be especially vigilant about being checked for melanoma.

Immunosuppressed Patients More Prone to Melanoma

A study published in Mayo Clinic Proceedings (October 2012) found that melanoma is more common in immunosuppressed patients, including patients with a prior solid organ transplant, patients with lymphoma, and patients with HIV/AIDS.

Agnieszka Kubica, BS, and Jerry D. Brewer, MD, of the Mayo Clinic conducted a comprehensive literature search of PubMed with no date limitation, reviewing most pertinent studies on the topic of melanoma and terms including immunosuppression, immunocompromise, genetics, antigen processing, UV radiation, organ transplantation, radiation, and HIV/ AIDS. Included studies were generally large (>1000 patients in organ transplant studies and ≥500 patients in lymphoma studies). The data show that overall survival is worse in organ transplant recipients who have melanoma, independent of Breslow thickness or Clark level. Overall survival is 2.5 times worse in patients with chronic lymphocytic leukemia who have melanoma; these patients are 2.8 times more likely to die of metastatic melanoma. Melanoma is also more common in patients with HIV infection/AIDS, but the factors that influence disease course remain unclear.

Immunosuppressed patients who have melanoma require frequent dermatologic evaluation, sun protection, and education about the potentially worse clinical course of their disease.

Fast Fact: Over the past 40 years, US rates of melanoma increased by 800% among young women and 400% among young men.