Melanoma Risk Doubled for Monoclonal B-Cell Lymphocytosis

Patients who have the low-count chronic lymphocytic leukemia (CLL) phenotype monoclonal B-cell lymphocytosis (LC-MBL) have a nearly doubled risk for melanoma, according to a study in Journal of Clinical Oncology.¹

MBL is a premalignant condition that is roughly 500 times more common than CLL, which itself is associated with a 2-fold increased risk of melanoma. It had been unknown whether patients who have MBL had an increased melanoma risk.

“Given that unrecognized MBL is prevalent in approximately 5% to 12% of the US population older than 40 years, these results have meaningful effect on melanoma rates in the population. An] estimated 5% to 10% of individuals with incident melanoma could be associated with underlying MBL,” the authors wrote.

Study participants included 7334 Mayo Clinic Biobank patients 40 years or older with no previous hematological malignancies. Slightly more than a third of patients were male, and the median age at MBL screening was 67 years.

Eight-color flow cytometry was used to screen for MBL, and patients P were classified as LC- MBL or high-count MBL, based on clonal B-cell percent.

Of all participants, 1151 individuals had CD5-positive MBL. Within this group, 1098 had LC-MBL. After a median follow-up of 3.2 years, 131 participants developed melanoma, and 36 of these patients were positive for MBL. The estimated 5-year cumulative incidences of melanoma were 3.4% and 2% among those with and without MBL, respectively.

Melanoma is the fifth most common cancer in the US. | Image Credit: © Monstar Studio-stock.adobe.com

Patients with MBL were found to have a 1.86-fold risk of melanoma, after adjusting for age, sex, and history of previous melanoma. This higher risk was the same for patients without a history of melanoma. Patients with LC-MBL had a 1.92-fold increased risk of developing melanoma overall, and a 2.74-fold increased risk of early-stage melanoma, compared with those who did not have MBL.

Although the risk of melanoma was higher among patients with MBL , the stage and Breslow thickness at the time of melanoma diagnosis were similar to patients who did not have MBL. There was an elevated but nonsignificant risk of death among patients with melanoma with MBL.

Melanomas in patients with CLL are typically detected at a late stage and belong to a more aggressive disease phenotype compared with melanomas in patients without CLL. It has been hypothesized that the greater risk of melanoma in patients who have CLL is caused by underlying immune dysfunction andgenetic susceptibility, and is an adverse event after chemotherapy. Some evidence also links the increased risk of melanoma to patients with CLL with T-cell–activating autoimmune conditions like Graves’ disease and psoriasis. Existing research suggests that some of these immune defects are active at the MBL phase.

Melanoma is the fifth most common cancer in the US, with 1.4 million people affected in 2020, according to the study, and is increasing in people under 40, especially women, according to the Mayo Clinic.² CLL is the most common leukemia in the US and has been rising worldwide over the past few decades, mainly in countries with fair-skinned populations and high levels of sun exposure. The 5-year relative survival rate for CLL is 87.7%., but this figure drops to 31.9% when diagnosed at an advanced stage.

“[In] the largest cohort of individuals screened for MBL reported to date, we found that LC-MBL, a common condition in the general population, was associated with a 92% elevated risk of incident melanoma, similar to the approximately 2-fold increased risk observed in patients with CLL. These results suggest that the increased risk of melanoma among individuals with CLL appears to begin with the onset of MBL,” the authors stated. “These data, together with our previous findings of a heightened risk of serious infections, suggest that, although they have low risk of progression to CLL or other lymphoid malignancies, individuals with LC-MBL are at an increased risk of adverse health outcomes.”

References

1. Vallejo BA, Ansari A, Parikh SA, et al. Risk of incident melanoma among individuals with low-count monoclonal B-cell lymphocytosis. J Clin Oncol. 2024:JCO2400332. doi:10.1200/JCO.24.00332

2. Melanoma. Mayo Clinic. Accessed Sept. 18, 2024. https://www.mayoclinic.org/diseases-conditions/melanoma/symptoms-causes/syc-20374884#:~:text=deeper%20skin%20layers.-,Melanoma%20is%20a%20kind%20of%20skin%20cancer%20that%20starts%20in,%2C%20back%2C%20face%20and%20legs