People with chronic lymphocytic leukaemia (CLL) have a sizeable 600% higher risk of the most dangerous form of skin cancer, melanoma, researchers have found.

As a result of this discovery, data from several international research studies recommends clinical teams caring for CLL patients actively monitor for melanoma as part of routine care, so skin cancer is identified early and managed with targeted therapies. 

Management of melanoma in patients with chronic lymphocytic leukaemia 

The most likely cause of CLL patients being more susceptible to melanoma is their suppressed immune systems, according to haematologist, internationally recognised researcher and CLL expert, Dr Clive Zent, from the University of Rochester Medical Center in the U.S. 

“Normally, in people with healthy immune systems, malignant skin cells might be detected and destroyed before they become a problem. But in CLL patients, failure of this control system increases the rate at which cancer cells can grow into tumours, and the likelihood that they will become invasive or spread to distant sites,” said Dr Zent. 

He was commenting on a study by a Wilmot Cancer Institute scientific team, which he led, that discovered a 600% higher risk of melanoma in a large group of people with CLL when compared to a similar group of age- and gender-matched people from the general population. The study results showed 22 melanomas diagnosed among the cohort of 470 people.  

Although a higher risk of melanoma had been shown, this study (published in Leukemia Research in 2018) was the first report of analysis of detection rate and treatments among CLL patients. 

Risk factors for skin cancer and solid tumours in newly diagnosed CLL and the impact of skin surveillance 

The following year, an article published in Leukemia & Lymphoma on a retrospective Canadian study of 587 newly diagnosed CLL patients found they were four to five times more likely to develop aggressive skin cancers one year after their CLL diagnosis. Skin cancer was developed in 28% of the study cohort – about a third before being diagnosed with CLL and two thirds after their diagnosis. 

The first skin cancers began to increase five to six years before the CLL diagnosis but continued to increase after diagnosis. There was a disproportionate increase in the rate of melanomas (four-fold) and squamous cell carcinomas (five-fold) compared to a three-fold increase in basal cell carcinomas. 

The researchers said the increased number of skin cancers was a result of the haematological malignancy (CLL), demonstrating the immunosuppression that predisposes these patients to skin cancer is present prior to the diagnosis of CLL. 

Men aged 70 or older, and receiving chemotherapy, were predictive factors for the development of skin cancer. 

The study also found 27% of CLL patients developed a solid tumour including breast, prostate, lung, colon, and bladder cancers. These cancers were the major cause of death during the seven-year follow-up period, ahead of CLL and infections. 

Development of a skin cancer did not increase the risk of developing a subsequent solid tumour and only 10% of patients developed both. 

Chronic lymphocytic leukemia, skin and other second cancers 

Commentary on this research by Australians, Professor Stephen Mulligan, Associate Professor Stephen Shumack, and Associate Professor Alexander Guminski, said immune failure in CLL leading to infection and second malignancy arguably now limits overall survival more than the CLL itself.   

They said CLL patients at Royal North Shore Hospital (Sydney) have a higher rate of mortality from non-haematological malignancy than from their CLL. 

“As the survival from better CLL disease control improves further, second malignancy will likely become an even more dominant factor for long-term survival for a higher proportion of patients, and it will require more focus from the CLL community.” 

They noted the different UV exposure in Canada compared to Australia, and said, “In Australian CLL patients, this translates into an NMSC [non-melanoma skin cancer] mortality rate 17 times that of the general population”. 

In response, combined CLL and dermatology clinics “provide an ideal environment and opportunity to educate patients regarding the need for strict sun avoidance as well as their regular surveillance, and rapid, multidisciplinary intervention when skin cancer occurs”. 

The risk of melanoma in patients with chronic lymphocytic leukemia; a population-based study 

A more recent population-based study of the risk of melanoma in CLL patients included patients diagnosed between 2000 and 2015 and registered in the Surveillance, Epidemiology and End Results (SEER) database of the U.S. National Cancer Institute.  

According to the research paper published in the journal, Current Problems in Cancer, most of these patients were males (77.6%), white (98.2%), married (62.2%), and aged between 65-84 years when diagnosed with CLL.  

Of the 48,876 CLL cases reviewed, 474 developed a second primary melanoma of the skin. The increase in melanoma risk was higher within the first five years following CLL diagnosis and it was higher in males compared to females and in people aged 45-64 years. Analysis also showed that of the 7827 CLL patients receiving chemotherapy, 70 later developed melanoma. 

It was noted that out of 1048 CLL cases observed in Asian patients, none of the cases was later followed by a melanoma. 

The study concluded that CLL increases the risk of developing melanoma, so it is crucial to keep rigorous screening, high-suspicion, and close follow-up for recurrence in consideration while managing these patients. 

Also, that further research is required to better understand how immunosuppressive agents and immune-modulating biological medications affect the course of treatment and to assess the need to reduce these drugs in certain settings. 

Acknowledgment: the limbic was a source of information for this article.