Treatment Outcomes of Immune-Related Cutaneous Adverse Events.

PURPOSE: The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics. METHODS: A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed. RESULTS: A total of 285 patients (median age, 65 years [range, 17 to 89 years]) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype (P = .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74 v 0.71; P < .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1; P = .043). CONCLUSION: Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.

Managing Pulmonary Toxicities Associated with Immunotherapy: A Case Discussion.

Immunotherapy has changed the field of oncology around the world with the approval of immune checkpoint inhibitors for a number of tumor types over the last 5 years. However, immune-mediated adverse events can be challenging and difficult to treat, with one of the most dire consequences being immune-mediated pneumonitis. KEY POINTS: Rapid intervention and aggressive management for grade 3 or greater pneumonitisSlow taper of steroids and also recommend pneumocystis carinii pneumonia prophylaxisMonitor carefully for a pneumonitis flare with steroid taper, which can occur in the absence of resuming anti-programmed cell death protein 1 (PD-1) [1], and do not resume anti-PD-1 therapy until completely off steroids and no clinical or radiologic evidence of recurrenceConsider observation without anti-PD-1 resumption-in this case, durable response was maintained even without resuming anti-PD-1 therapy.

Targeting immune checkpoints in melanoma: an update.

Different treatment modalities encompassed under the term 'immunotherapy' have led to major breakthroughs in the treatment of melanoma. Immune checkpoint-blocking antibodies targeting CTLA-4 and PD-1 result in significant activity and prolonged survival in patients with advanced melanoma and are currently available for clinical use. Studies addressing novel immune checkpoint blocking antibodies, combined approaches and predictive/prognostic biomarkers are expected to broaden the applicability and efficacy of this approach. In this article, we will review clinically meaningful aspects of immune checkpoint blockade, promising strategies under development and the challenges faced in a continuous search to improve the outcomes of patients affected by this disease.