Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma

Abstract

Objectives: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with higher incidence among whites, elderly, and immunosuppressed patients. Although immunosuppressed MCC patients are at higher risk of recurrence and MCC-related death, it is unknown whether immunosuppression type is associated with differential outcomes. Materials and Methods: We retrospectively evaluated 89 nonmetastatic MCC patients with a diagnosis of chronic immunosuppression. Immunosuppression was categorized as chronic lymphocytic leukemia (31% of cohort), other hematologic malignancies (18%), solid organ transplant (21%), autoimmune disease (21%), and human immunodeficiency virus acquired deficiency syndrome (8%). Progression-free survival (PFS) and MCC-specific survival (MSS) were estimated with the cumulative incidence function. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: With a median follow-up of 52 months, 53 deaths occurred (42 from MCC, 7 unknown, and 4 non-MCC). Two-year PFS, MSS, and OS were 30%, 55%, and 52%, respectively. Human immunodeficiency virus/acquired deficiency syndrome and solid organ transplant patients were diagnosed with MCC at a younger age (median 55 and 59 y, respectively) and with more advanced stage disease compared with other immunosuppressed subgroups. PFS did not significantly differ among the 5 immunosuppression subgroups (P=0.30), but significant differences were observed in MSS and OS (both P=0.01). Controlling for potential confounders for OS, including age and stage, immunosuppression type was still significantly associated with risk of death (P=0.01). Conclusions: Among immunosuppressed MCC patients, recurrent MCC is the major cause of mortality. The risk of death from MCC differs among immunosuppression types, suggesting important biological differences in host-tumor immune interactions.

Paraneoplastic neurological syndromes: clinical presentations and management

“…This has been demonstrated in studies analyzing effect immunosuppression on Merkel cell cancer and cutaneous squamous cell cancer of head and neck. 108,109 In patients with cutaneous squamous cell carcinoma, immunosuppression was associated with worse 5-year disease-specific survival (68% versus 84%) and overall survival (37% versus 59%). 108 However, a considerable number of these patients had immunosuppression secondary to medical comorbidities, such as lymphoma or leukemia (27%) and HIV (2%), rather than immunosuppressive medications.…”

Merkel Cell Carcinoma of the Head and Neck: Epidemiology, Pathogenesis, Current State of Treatment and Future Directions

“…Immunosuppression has been shown in multiple studies to be a negative independent prognostic factor for patients with MCC [24,28,29,39,40]. With regard to differential impact on clinical outcomes by etiology of immunosuppression in MCC, Cook et al [41] performed a retrospective analysis of 89 patients with non-metastatic MCC and found increased mortality risk for immunosuppressed patients with HIV/AIDS and organ transplant relative to patients with autoimmune disease (reference group). In an analysis of the NCDB, Yusuf et al found immune status to be an independent predictor of OS for patients with MCC by MVA, and found etiology of immunosuppression to be associated with OS with the lowest 3-year OS rates for immunosuppressed patients with solid organ transplants [24].…”

Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis

“…Between 2000-2013, there was a 95% increase in reported cases of MCC, as compared to a 15% increase in all solid tumors, and its incidence has quadrupled during the past 20 years [4]. Merkel cell polyomavirus (MCPyV) [5], ultraviolet (UV) exposure [6], and immuno-suppression [7] are known major risk factors. Although immune checkpoint inhibitors (ICIs) targeting programmed cell death protein one and its ligand (PD1/PD-L1) have become the standard of care for advanced MCC, resistance develops in the majority of treated patients [8][9][10][11].…”