Elsevier

Leukemia Research

Volume 71, August 2018, Pages 43-46
Leukemia Research

Research paper
Management of melanoma in patients with chronic lymphocytic leukemia

https://doi.org/10.1016/j.leukres.2018.07.003Get rights and content

Highlights

  • CLL patients have a significantly higher risk of invasive melanoma.

  • Most melanomas (68.2%) were detected through active surveillance in a dermatology clinic.

  • Most melanomas (77.3%) were detected at a non-advanced stage.

  • Active surveillance for melanoma leading to early excision could be beneficial.

  • Ibrutinib and pembrolizumab was effective therapy for progressive CLL and metastatic melanoma.

Abstract

Melanoma is significantly more common and is associated with a poorer prognosis in patients with an underlying B-cell malignancy. This study reports on the management of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) and a subsequent diagnosis of melanoma. In the Wilmot Cancer Institute CLL cohort, which includes 470 patients followed for 2849 person-years, 18 patients (3.8%) developed 22 melanomas. Fourteen melanomas were invasive, a significantly higher rate as compared with the age and sex matched general population (standardized incidence ratio [SIR] 6.32 (95% CI 3.45; 10.60). Melanomas were most often detected (n = 15; 68.2%) through active surveillance in a dermatology clinic. Most melanomas (n = 17; 77.3%) were detected at a non-advanced stage (pathological stage grouping < III). The most common management was wide local excision without sentinel lymph node biopsy (n = 13, 59.1%). Management for the 4 (18.2%) patients with metastatic disease included the immune checkpoint inhibitor (ICI) pembrolizumab (n = 1), systemic chemotherapy with dacarbazine (n = 1), and palliative care (n = 2). The patient treated with ICI is in sustained remission of her melanoma after 23 cycles of therapy while her TP53 disrupted CLL continues to respond to ibrutinib therapy. We conclude that patients with CLL may benefit from active surveillance for melanoma leading to early excision of locally-manageable disease. In patients with metastatic melanoma, combined treatment with targeted kinase inhibitors and ICIs can be successful and tolerable. Larger prospective studies should be considered to further evaluate these approaches.

Introduction

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is the most prevalent lymphoid malignancy in the United States, with approximately 140,000 people living with the disease [1]. Immune dysfunction is an early and clinically important complication of CLL [2]. Patients with CLL are at significantly increased risk of skin cancer including melanoma, and have a ∼2-fold increased risk of mortality from these second malignancies compared to patients without a preceding diagnosis of CLL [[3], [4], [5], [6], [7]]. As a result, patients with a diagnosis of CLL are often recommended to undergo routine skin cancer examinations because melanomas detected by health care providers or by a routine surveillance program have better outcomes than those who present due to symptomatic lesions [8]. In addition, for patients with metastatic melanoma, the introduction of immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes. However, patients with a second malignancy were excluded from these clinical trials [9] so there is limited data on the efficacy of these treatments for metastatic melanoma in the CLL patient population. In this observational study, we investigated how melanomas were detected and managed in a single regional CLL patient population to provide data on the utility of active monitoring for melanoma and report that ICI could have a role in management of advanced disease in this population.

Section snippets

Study subjects

The Wilmot Cancer Institute (WCI) CLL cohort includes all consenting CLL and clinically detected CLL immunophenotype monoclonal B cell lymphocytosis (MBL) patients diagnosed using standard criteria [10] managed at the University of Rochester Medical Center (URMC). This is an open cohort, where participants may enter and leave at any point, and information is collected while they are managed at WCI. All 470 CLL cohort patients seen in the WCI Lymphoma/CLL clinic between 1 May 2000 and 1

Results

A total of 470 patients (461 CLL, 9 MBL) contributed 2849.3 years of follow-up (Table 1). Except for younger age at diagnosis, the patient characteristics were typical for an unselected CLL population with no significant differences between patients with and without melanoma [16].

Eighteen (3.8%) of the 470 patients in the cohort had 22 melanomas detected during the observation period with 7 (33.3%) detected at the in situ stage (pathologic stage 0), 8 (38.1%) at pathologic stage I, 2 (9.5%) at

Discussion

To the best of our knowledge, this study is the first comprehensive analysis of the detection and treatment of melanoma in a clinical cohort of patients with CLL. We also report the successful treatment of metastatic melanoma with pembrolizomab in a patient with CLL on ibrutinib therapy.

Consistent with previously published data, our study found a significantly higher rate of detection of melanoma (SIR 6.32,95% CI 3.45–10.60) in CLL patients compared to an age and sex matched general population [

Acknowledgments

The authors would like to thank the consenting CLL patients who made the study possible.

Funding

This work was funded by the Cadregari Endowment at the University of Rochester’s Wilmot Cancer Institute.

References (19)

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    A higher incidence of various visceral carcinomas occurs in CLL patients compared with age-matched populations.6,8-11 Cutaneous SPNLM exhibiting this higher incidence include Merkel cell carcinoma,7,12-16 squamous cell carcinoma,17-20 and malignant melanoma.21-24 In addition, there is an elevated risk for the development of non-epithelial malignancies such as Kaposi sarcoma among CLL individuals.16,25

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    This is crucial for survival as several studies have reported worse clinical outcomes and more aggressive cancerous cells in patients with melanoma diagnosed after lymphoma compared to patients with lymphoma alone or melanoma alone; the overall survival of patients with melanoma – at early stages – is estimated to be 96%-99%, while patient with melanoma after CLL have a survival rate of 60%.2,6,13 In addition, a study demonstrated the significance of active surveillance in a population of CLL patients, in which the risk of melanoma appeared to be significantly higher in comparison to the general population.14 The effect of CLL's chemotherapy on the development of melanoma or the survival of these patients is controversial.

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