Prior Treatment with Chemotherapy Is Associated with Poor Outcomes of High Risk Skin Cancers in Patients with Chronic Lymphocytic Leukemia
Authors: Davids Matthew S. , Velez Nicole F. , Karia Pritesh , Guo Ye , Vartanov Alexander R. , Neel Victor A. , Brown Jennifer R. , Schmults Chrysalyne D. 
Published: October 2019

Abstract
Abstract 3920
The increased incidence of skin cancer in patients with chronic lymphocytic leukemia (CLL) has been well-documented; however, the outcomes for CLL patients with high risk skin cancers are not as well-characterized. Moreover, little is known about the association between outcomes of high risk skin cancers and CLL prognostic factors or exposure to prior chemotherapy.
We identified 225 patients at our institutions over the last 20 years with concurrent CLL and skin cancer, and we retrospectively examined outcomes for the 139/225 (61.8%) who had high risk skin cancer as defined by a diagnosis of squamous cell carcinoma (SCC), melanoma, or Merkel cell carcinoma (MCC). Poor skin cancer outcome (defined by local recurrence, nodal metastasis, and disease specific death) was determined by review of patient medical records and verified by pathology reports. Associations between various risk factors and poor skin cancer outcomes were evaluated via chi-square statistics (STATA 12.0 College Station, TX).
The study group included a representative CLL population, with 98/139 (70%) males and a median age at diagnosis of 65 years (range 35–84), with a median follow-up of 120 months (range 2–410). Over the course of the study, 76 CLL patients remained alive (55%), 16 patients died due to CLL (12%), and 42 patients died from other causes (30%), including 18 (13%) from skin cancer. Median age at time of skin cancer diagnosis was 72 years (range 44–98), and median follow-up time after skin cancer diagnosis was 41 months (range 2–182). Skin cancer diagnoses included SCC in 122 patients (81%), melanoma in 22 patients (13%), and MCC in 8 patients (6%). Sixty-three (45%) patients had more than one skin cancer diagnosed. In the 122 patients with SCC, there were a total of 353 tumors, 297 of which occurred in males (84%). Half of the SCCs were in the head and neck (n=175, 49.6%). Fifty-four SCCs (15%) were greater than 2 cm in diameter. Rates of nodal metastases and death due to SCC were 12% and 6%, respectively. In the 22 patients with melanoma, 14 occurred in men (63.6%), with the largest number of tumors again located on the head and neck (n=8, 36.4%). Breslow thickness was greater than 1 mm in 12 patients (54.5%). Local recurrence and nodal metastases each occurred in 5 patients (22.7%). The five patients (22.7%) who died due to melanoma were the same patients with nodal metastases. In the 8 patients with MCC, 5 patients (62.5%) were male, and there was no location predominance. Five tumors (62.5%) were greater than 2 cm at time of diagnosis, local recurrence occurred in 1 patient (12.5%), and 5 patients (62.5%) had nodal metastases, with 4 of these 5 dying from MCC. Interestingly, prior treatment with any CLL chemotherapy was significantly associated with poorer skin cancer outcome, with increased rates of local recurrence, metastatic disease, or death due to skin cancer (p=0.001). We also explored whether high risk CLL prognostic factors were associated with poorer skin cancer outcomes. Eleven out of 18 patients tested (61%) had unmutated IGHV, 9/69 patients tested (13%) had del(17p) or del(11q) cytogenetics, and 71 patients did not have prognostic marker data available. In this limited prognostic marker data set, neither unmutated IGHV, poor risk cytogenetics, nor advanced Rai stage was associated with skin-cancer specific outcomes.
Overall, the majority of the skin cancers in our cohort occurred in males, and the most common site of disease was the head and neck, highlighting an area in need of especially close surveillance. Relative to the historical experience of high-risk skin cancer patients in the general population, we found skin cancers in our CLL population to be more aggressive. For example, 2 of the skin-cancer related deaths were in CLL patients with stage I melanoma, which is unusual in the general population. Additionally, rates of nodal metastases and death in our SCC group were 12% and 6%, respectively, compared to rates of 4% and 2% in most studies of SCC in the general population. Strikingly, the risk of death from skin cancer was equivalent to the risk of death from CLL. The poor skin cancer outcomes in patients in our study were driven by the group who had received prior chemotherapy. Outcomes were not influenced by high risk CLL prognostic markers, although this latter analysis was limited by incomplete data.

Disclosures:
No relevant conflicts of interest to declare.