Although routinely recommended, nicotinamide does not prevent nonmelanoma skin cancers in solid-organ transplant patients, according to a randomized trial published March 2 in The New England Journal of Medicine.
“No signal of efficacy was observed,” said investigators led by Nicholas Allen, MPH, of the University of Sydney Department of Dermatology, in Australia.
These results fill an “important gap in our understanding” and “will probably change the practice of many skin-cancer physicians,” two experts on the topic commented in a related editorial.
The editorialists are David Miller, MD, PhD, a dermatologist and medical oncologist at Massachusetts General Hospital, and Kevin Emerick, MD, a head and neck surgeon as Massachusetts Eye and Ear, both in Boston
Transplant patients have 50 times the risk of nonmelanoma skin cancers ― also known as keratinocyte cancers ― than the general public, owing to immunosuppression, and their lesions are more aggressive and are more likely to metastasize, they explain.
Nicotinamide (vitamin B3) has been shown to prevent nonmelanoma skin cancers in healthy, immunocompetent people, so physicians routinely prescribe it to transplant patients on the assumption that it will do the same for them, they comment.
The Australian investigators decided to put the assumption to the test.
The team randomly assigned 79 patients who had undergone solid-organ transplant to receive nicotinamide 500 mg twice a day and 79 other patients to receive twice-daily placebo for a year. Participants underwent dermatology exams every 3 months to check for new lesions.
The participants were at high risk for new lesions; some had had more than 40 in the previous 5 years. The two groups were well balanced; kidney transplants were the most common.
At 12 months, there was virtually no difference in the incidence of new nonmelanoma skin cancers: 207 in the nicotinamide group and 210 in the placebo group (P = .96).
There was also no significant difference in squamous cell and basal cell carcinoma counts or actinic keratosis counts.
“The interpretation of the results is straightforward: nicotinamide lacks clinical usefulness in preventing the development of keratinocyte carcinomas in solid-organ transplant recipients,” the team concludes.
As for why nicotinamide didn’t work in the trial, the investigators say it could be because it is not potent enough to overcome the stifling of antitumor immunity and DNA-repair enzymes with immunosuppression.
Fewer than half of participants in the trial reported using sunscreen at any point during the study, which is in line with past reports that transplant patients don’t routinely use sunscreen.
Two other strategies for preventing squamous cell carcinoma after transplant ― use of oral retinoids and mTOR inhibitors ― are problematic for various reasons, and use was low in both study arms.
Editorialists Miller and Emerick suggest a possible new approach: immune checkpoint inhibitors before transplant to reduce the risk of nonmelanoma skin cancer afterward. They say the strategy should be explored and that ongoing efforts to minimize or eliminate the need for immunosuppression after transplant are promising.
The investigators originally planned to enroll 254 persons, but the trial was stopped early because of poor recruitment. Potential participants may already have been taking nicotinamide, which is commonly used, and that may have affected recruitment, the investigators say.
The work was funded by Australia’s National Health and Medical Research Council. Allen has disclosed no relevant financial relationships. One investigator has received speaker’s fees from BMS. Another is a consultant for many companies, including Amgen, BMS, GlaxoSmithKline, and Merck. Emerick is an advisor for Regeneron, Sanofi, and Castle Biosciences. Miller is a researcher or consultant for those companies as well as Pfizer and others and has stock options in Avstera.
N Engl J Med. Published March 2, 2023. Abstract, Editorial
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]
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