Autoimmune comorbidities in patients with metastatic melanoma: a retrospective analysis of us claims data

Abstract

BackgroundImmunotherapies have advanced the treatment of metastatic melanoma; however, they are associated with immune-related toxicities. Patients with pre-existing autoimmune comorbidities are commonly excluded from clinical trials investigating immunotherapies in metastatic melanoma. Since information on pre-existing autoimmune comorbidities in “real-world” patients with newly diagnosed metastatic melanoma is limited, we sought to estimate the prevalence of autoimmune comorbidities and its change over time.MethodsData were obtained from a large US claims database, MarketScan®, from 2004 to 2014. Records of patients with newly diagnosed metastatic or non-metastatic melanoma and of general population were analyzed. Autoimmune comorbidities were defined as presence of autoimmune disorders, which were obtained from the list of diseases at the American Autoimmune-Related Diseases Association web portal (www.aarda.org). The prevalence of pre-existing autoimmune comorbidities and its change over the 11-year period were calculated. Logistic regression analyses were performed to evaluate the relationship between clinical and demographic factors and pre-existing autoimmune comorbidities in patients with metastatic melanoma.ResultsThis study assessed the prevalence and change of prevalence over a period of 11 years of 147 autoimmune comorbidities. Among 12,028 patients with newly diagnosed metastatic melanoma, the prevalence rate of pre-existing autoimmune comorbidities increased from 17.1% in 2004 to 28.3% in 2014 (P < 0.001). The prevalence rates of autoimmune comorbidities increased from 11.7% in 2004 to 19.8% in 2014 in patients with non-metastatic melanoma and 7.9% in 2004 to 9.2% in 2014 in the general population. In addition, patients with bone or gastrointestinal melanoma metastases, those with more comorbid diseases, or female patients, were found to have a higher risk of autoimmune comorbidities.ConclusionsThe prevalence of pre-existing autoimmune comorbidities in patients with newly diagnosed metastatic melanoma was high, and increased over 11 years. In comparison, a lower prevalence of autoimmune comorbidities was seen in patients with newly diagnosed non-metastatic melanoma and in the general population. Increases in prevalence for these population groups were also observed over 11 years. Impact of autoimmune comorbidities on treatment decisions in patients with metastatic melanoma should be explored.

Real-world experience with pembrolizumab in patients with advanced melanoma

“…Examination of a large US claims database from 2004 to 2014 found that the prevalence rate of pre-existing autoimmune comorbidities was 28% among 1177 patients with newly diagnosed metastatic melanoma in 2014, a prevalence higher than that in patients with non-metastatic melanoma and in the general population. [39] In our study, we found no significant difference in OS with regard to the presence or absence of an autoimmune condition (8% of patients had pre-existing autoimmune diagnoses). A recent systematic review of case reports and observational studies of patients with cancer found no differences in adverse events between those who had active vs. inactive autoimmune disease and who were prescribed an immune checkpoint inhibitor (ipilimumab or a PD-1/PD-L1 inhibitor); nonetheless, the authors [28] and others [40] have called for more research to establish the risk:benefit ratio of checkpoint inhibitors in this patient population.…”

An update on the safety of nivolumab for the treatment of advanced melanoma

“…Phase 1 trial is currently recruiting such patients (NCT03816345) including patients with varying severity of dermatomyositis (DM)/systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) (ulcerative colitis [UC] and Crohn's disease [CD]), multiple sclerosis (MS), Sjogren's syndrome (SjS), and other autoimmune diseases. In fact the prevalence rate of autoimmune disorders in melanoma patients ranges between 17% and more than 28%; with myositis, peripheral neuropathies, type 1 diabetes mellitus, rheumatoid arthritis and psoriasis being the most common [77]. Some case and case series confirm the safety of nivolumab usage in individuals with autoimmune disease including rheumatoid arthritis and myastenia [78,79].…”

STAT3 and STAT5 Targeting for Simultaneous Management of Melanoma and Autoimmune Diseases

“…Other autoimmune diseases are positively correlated with melanoma progression [2,26]. A retrospective meta-analysis assessed that the prevalence of pre-existing AD in melanoma patients increased by 1.7-fold within a decade.…”

“…Cancer immunotherapy approaches include (a) checkpoint inhibitors, which act by releasing the brakes that prevent T-cells from killing cancer cells, (b) monoclonal antibodies, that are designed to attach to cancer cell-specific antigens, (c) cancer vaccines, boosting the immune system’s response to tumors, or (d) cell-based therapies, such as chimeric antigen receptor (CAR) T-cell therapy, where T cells taken from a patient’s tumor are expanded and/or genetically engineered ex vivo and then administered back to the patient, a process termed adoptive transfer [1]. The field of successful application of immunotherapy includes, but is not limited to, metastatic melanoma [2], a type of cancer that arises from melanocytes and represents the deadliest form of skin cancer, with increasing prevalence. Once it becomes metastatic, the prognosis is very unfavorable and, thus, early diagnosis is crucial for effective management [3].…”

“…Since 2011, several next-generation immune-based formulations, such as the checkpoint inhibitors ipilimumab, pembrolizumab, and nivolumab, received approval by the Food and Drug Administration (FDA) for the indication of metastatic melanoma [2] and led to significant clinical improvements, either as monotherapies or in combination regimens [4]. However, despite their remarkable success, only up to 20% to 30% of patients have benefited from these treatments, while the rest are either non-responders (primary resistance) or partial responders (acquired resistance).…”