Melanoma and non‐melanoma skin cancers in hairy cell leukaemia: a Surveillance, Epidemiology and End Results population analysis and the 30‐year experience at Memorial Sloan Kettering Cancer Center

Abstract

Few studies have examined melanoma and non-melanoma skin cancer (NMSC) incidence rates after a diagnosis of hairy cell leukaemia (HCL). We assessed 267 HCL patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) and Surveillance, Epidemiology and End Results (SEER) data for melanoma and NMSC incidence rates after HCL. Incidence data from MSKCC patients demonstrated a 10-year combined melanoma and NMSC skin cancer rate of 11.3%, melanoma 4.4% and NMSC 6.9%. Molecular analysis of skin cancers from MSKCC patients revealed activating RAS mutations in 3/9 patients, including one patient with melanoma. Of 4,750 SEER patients with HCL, 55 (1.2%) had a subsequent diagnosis of melanoma. Standardized incidence ratios (SIRs) did not show that melanoma was more common in HCL patients versus the general population (SIR 1.3, 95% CI 0.78–2.03). Analysis of SEER HCL patients diagnosed before and after 1990 (approximately before and after purine analogue therapy was introduced) showed no evidence of an increased incidence after 1990. A better understanding of any potential association between HCL and skin cancer is highly relevant given ongoing trials using BRAF inhibitors, such as vemurafenib, for relapsed HCL, as RAS-mutant skin cancers could be paradoxically activated in these patients.

Analysis of a cohort of 279 patients with hairy-cell leukemia (HCL): 10 years of follow-up

“…In other studies, HCL patients did not have a higher risk of developing a second cancer (Table 5) [21][22][23][24]40,43,50 . Some studies found an excess of risk only for certain cancers (Table 5) [51][52][53] .…”

Treatment outcomes and secondary cancer incidence in young patients with hairy cell leukaemia

“…The effect of patient age has not been assessed as a factor for predicting secondary cancers in this disease. A study from our group showed that HCL treated after the introduction of cladribine did not measurably increase the incidence of melanoma beyond the expected population rate (Watts et al , ); however, patients were not stratified by age at diagnosis in this report, which may be relevant given the differences in lifestyle and cumulative ultraviolet exposure in younger individuals (Watts et al , ). The issue of skin malignancy was of particular concern in the phase 2 study of vemurafenib, which resulted in investigators limiting drug exposure to 6 months because of concerns that BRAF inhibition could, paradoxically, increase the growth of RAS ‐mutated cancers (Su et al , ).…”

Potential breakthroughs with investigational drugs for hairy cell leukemia

“…A recent study by Watts et al reported no statistically significant increased risk of melanoma in HCL patients, compared to the general population [88]. Vemurafenib can further increase the incidence of secondary skin cancer events.…”