The Use of Nicotinamide to Prevent Nonmelanoma Skin Cancers in Patients With Chronic Lymphocytic Leukemia

Deborah Stephens, DO, Huntsman Cancer Institute, University of Utah, discusses her presentation from the 2023 NCCN Annual Conference on the use of nicotinamide to prevent nonmelanoma skin cancers in patients with chronic lymphocytic leukemia.

Deborah Stevens, DO: Hi there, my name is Deborah Stephens, and I'm an Associate Professor at the Huntsman Cancer Institute at the University of Utah. I recently presented some of my work on nicotinamide in the prevention of skin cancer for patients with chronic lymphocytic leukemia at the annual NCCN conference.

Can you give some background about your study and what prompted you to undertake it?

Dr Stevens: In my clinical practice, the majority of patients are patients with chronic lymphocytic leukemia, and I see recurrently that patients present with very severe nonmelanoma skin cancers. These skin cancers are generally more severe than they are in a patient without chronic lymphocytic leukemia, and really, they can become metastatic and lead to a lot of different complications for these patients. Even disfiguring surgeries, even patients can die from complications of these nonmelanoma skin cancers. And these types of skin cancers are seen more commonly in patients with immunosuppression, and patients with CLL definitely have immunosuppression. However, there hasn't been a lot of work done looking at what is the exact mechanism of why these patients are at high risk for nonmelanoma skin cancers, and why we see so many recurrent and severe cancers in these patients?

I started at a few different angles, looking for is there anything we can do for skin cancer prevention? And there was a large clinical trial that was published with nicotinamide, which is a vitamin B3 derivative. Looking at patients, and these were patients without cancer or other immune compromising conditions, they looked at using nicotinamide, 500 milligrams twice daily, and they compared this to placebo and found that they could decrease the recurrence rate of nonmelanoma skin cancers by about 23%. So starting off, they thought this may be an immune modulating agent and might be worth studying in other populations. And so, that's where I thought it would be a great fit for CLL.

The other thing that I noted, we do a lot of genetic sequencing of patient samples with CLL, and there are actually other sequences that you can find within. If you subtract out the human sequences, you can find some other DNA sequencing. And we found a very high prevalence of beta human papillomavirus DNA signals within our CLL samples. And I thought that this potentially could be some sort of a link because the beta HPV virus has been associated with nonmelanoma skin cancers. And so, part of the impetus is to look at nicotinamide and see how it might modulate the immune system. And the other part of it is to gain more information on these skin cancers and what types of human papillomavirus might be involved in pathogenesis of these cancers.

What is your current hypothesis for the study?

Dr Stevens: Our current hypothesis for the study is that nicotinamide used 500 milligrams twice daily for one to two years, can reduce the recurrence risk for nonmelanoma skin cancer in patients with CLL. We also hypothesize that nicotinamide might help to modulate or improve immune responses as a part of preventing nonmelanoma skin cancer in these patients. We also want to look at the occurrence of different types of human papillomavirus, and we intend to do that by using skin cancer samples that are taken from the patients on study and sequencing them for the different viruses. And we are suspecting that there will be a set of viruses that are most likely associated with the skin cancer occurrences.

What are you hoping to learn from this research?

Dr Stevens: I really hope that our research is going to give us a lot of insight into the pathogenesis of nonmelanoma skin cancers in patients with CLL. And it's important now because our current recommendations for skin cancer screening are really a secondary prevention, in that we just tell patients to get skin exams one to two times annually. And so, this is catching the skin cancers after they already occur or catching pre-cancer states. I hope that the study can provide a method in actually to prevent the skin cancers from occurring in the first place for these patients. Hopefully, that will result in a really big decrease in their morbidity and mortality associated with the nonmelanoma skin cancers.

Looking ahead, what potential impact do you hope your findings will have on the standard of care, and or treatment for patients with chronic lymphocytic leukemia?

Dr Stevens: We hope that our study will find a proven method to reduce the risk of skin cancer occurrence in patients with chronic lymphocytic leukemia. And I hope that that would be integrated into the standard of care and into the NCCN guidelines if we can prove that this method can reduce the recurrence rate of nonmelanoma skin cancers. Also, I hope our research will lead to future projects where we can study different subsets. Maybe this could apply to other different types of lymphoma, or other patients with immune suppression. And I also hope we can identify some beta HPV viruses that we can either find a treatment or vaccine to prevent these viruses even from happening in the patients, and thus reducing the risk of skin cancer.

Is there anything else you would like to add?

Dr Stephens: I feel that this research is very important. Because patients with chronic lymphocytic leukemia do live for a long time with their disease and with the immunosuppression that's associated with it. Patients are always asking me, "Is there anything I can do to prevent CLL progression or complications of CLL?" And I think this would be a very easy way to prevent this, if proven to work. I think this could make a major impact in the lives of patients with CLL.