Strategies for Recognizing and Managing Immune-Mediated Adverse Events in the Treatment of Hodgkin Lymphoma with Checkpoint Inhibitors.

Abstract

The programmed death-1 (PD-1) receptor checkpoint inhibitors nivolumab and pembrolizumab represent an important therapeutic advance in the treatment of relapsed or refractory classical Hodgkin lymphoma (cHL). Clinical trials have shown substantial therapeutic activity and an acceptable safety profile in heavily pretreated patients, resulting in U.S. Food and Drug Administration approval of nivolumab for the treatment of cHL that has relapsed or progressed after either autologous hematopoietic cell transplantation (auto-HCT) and brentuximab vedotin treatment or three or more lines of systemic therapy (including auto-HCT), and of pembrolizumab for adult or pediatric patients with refractory cHL or cHL that has relapsed after three or more prior therapies. Mechanistically, anti-PD-1 therapy prevents inhibitory signaling through PD-1 receptors on T cells, thereby releasing a 'block' to antitumor T-cell responses. However, this disinhibition can also lead to inappropriate T-cell activation and responses against healthy tissues, resulting in immune-mediated adverse events (IMAEs) that affect a number of organ systems. The skin, gastrointestinal, hepatic, and endocrine systems are most commonly involved, typically resulting in rash, colitis, abnormal liver enzyme levels, and thyroiditis, respectively. Notably, pneumonitis is a potentially fatal complication of checkpoint inhibitor immunotherapy. Hematologic oncologists who treat cHL with PD-1 immune checkpoint inhibitors should monitor patients for IMAEs, as early recognition and treatment can rapidly reduce morbidity and mortality. This review focuses on IMAEs during the treatment of relapsed or refractory cHL with nivolumab and pembrolizumab. IMPLICATIONS FOR PRACTICE: This article highlights the importance of monitoring for immune-mediated adverse events (IMAEs) in patients with Hodgkin lymphoma (HL) who receive anti-programmed death-1 (anti-PD-1) therapy, with particular attention given to the recognition and management of such events. The risk of individual IMAEs differs between patients with HL and those with solid tumors, as prior treatments may predispose certain organ systems to specific IMAEs. Accurate and prompt diagnosis of IMAEs is essential for optimal management, allowing PD-1 inhibitor therapy to be restarted in order to maintain disease control. Potential difficulties, such as distinguishing disease progression from pneumonitis, or colitis from diarrhea, are highlighted to raise clinical awareness.