Insights from a Veterans Health Administration Database Analysis: Immune-Related Adverse Effects of Immunotherapy in Relapsed/Refractory Classical Hodgkin Lymphoma

Introduction: Despite the high success rates in treating Classical Hodgkin lymphoma (cHL), a specific group of patients still experience relapsed or refractory (R/R) disease, affecting approximately 10-20% of cases. The use of immunotherapy with checkpoint inhibitors (CPIs) has emerged as a promising approach, demonstrating impressive efficacy in R/R cHL patients [2,3]. However, there is a lack of real-world evidence regarding the immune-related adverse effects (irAEs) associated with immunotherapy in this relatively rare patient population. To address this gap, this study leverages the Veterans Health Administration (VHA) database to investigate irAEs, providing valuable insights to optimize treatment decisions.

Methods: A retrospective analysis was conducted on Hodgkin lymphoma patients who received immunotherapy from the VHA Corporate Data Warehouse from 2014-2022. Patients came from all 18 Veterans Integrated Service Networks, spanning all 50 states and US territories. Data was collected to determine the baseline characteristics, disease factors, detailed AE occurrence as well as outcomes in this cohort.

Results: The analysis included 68 cHL patients who received immunotherapy. The cohort had a mean age of 62.2 years (SD=15.9) and a median age of 66 years (IQR 54-72). The majority of the patients were male (97%) and White (80%) and only 6% of patients had a history of autoimmune disease. The distribution of patients across stages was as follows: Stage 1 (5%), Stage 2 (15%), Stage 3 (40%), and Stage 4 (40%). Additionally, 20% of patients underwent autologous stem cell transplantation (ASCT), with 10% receiving immunotherapy before transplantation and the remaining 10% receiving it post-transplant.

In our cohort, 31% had documented adverse effects related to immunotherapy. The most common adverse events observed were hematological/cytopenias (8%), dermatologic/rash (6%), endocrine-related (6%), pneumonitis (5%), hepatitis (2%), myocarditis (2%), and other adverse events (8%). Discontinuation of therapy due to irAEs occurred in 12% of patients. These findings align with prior literature, which has consistently reported thyroid gland dysfunction (such as hypothyroidism and thyroiditis) and rash as the most frequently observed immune-related adverse events [2]. The most common management of irAEs were holding therapy followed by use of corticosteroids.

Kaplan-Meier survival analysis revealed a median overall survival of 55.4 months (IQR=37.2-59.2), with a median follow-up time of 36.4 months (IQR=21.6 -58.6).

Conclusion: This study, utilizing the VA database, provides a distinctive and valuable perspective on irAEs associated with immunotherapy in cHL patients. By leveraging a comprehensive database on a large scale, this study significantly enhances our comprehension of immunotherapy in the context of cHL, thereby offering crucial guidance for treatment decisions concerning relapsed/refractory Hodgkin lymphoma patients. The findings of this study strongly indicate the sustained benefits of immune checkpoint inhibitors (ICI) in this population, emphasizing the importance of close patient monitoring to detect and manage immune-related adverse events at an early stage, thereby preventing life-threatening complications.