Introduction: Registry data indicate that 20% or more of Hodgkin lymphoma (HL) patients are ≥60; these HL patients have been labeled as elderly as their treatment has been associated with more toxicity, a higher relapse rate, and greater mortality relative to younger patients. The characteristics of HL in elderly patients differ from those in younger patients and may represent a biologically more aggressive disease. Further, elderly patients generally have a greater comorbidity burden than their younger counterparts, which may contribute to their under-representation in clinical trials. Nivolumab (NIVO) and pembrolizumab (PEMBRO) are both approved for treating relapsed/refractory HL based on studies that largely enrolled younger patients, as only about 10% of enrolled patients in the pivotal trials that led to their United States (US) Food and Drug Administration (FDA) approval were ≥60 years of age. Whether adverse events (AEs) related to these immunotherapies differ between younger and older HL patients is unknown and may have important clinical and practice implications. Therefore, we reviewed all post-marketing case reports from the FDA Adverse Events Reporting System (FAERS) Database involving NIVO or PEMBRO for HL and compared AEs and outcomes by age.
Methods: The FAERS database is a repository of anonymized reports for product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The database was queried for cases involving NIVO or PEMBRO (and their respective trade names) from the FDA approval date for the HL indication (May 17, 2016 for NIVO; March 14, 2017 for PEMBRO) through March 31, 2019. Cases were excluded if the age of the patient was unknown, or if the case was reported outside the US. Comparisons of rates of AEs by age group were made using Fisher's exact test; statistical significance was determined at a two-sided α=0.05.
Results: A total of 126 cases were retrieved (117 involving NIVO, 9 involving PEMBRO). One hundred and fourteen of the 126 cases (90%) were categorized as serious. Median age of all patients involved was 56 (range 10-89); 53 of the cases (42%) involved patients age 60 or older (Table). Overall, 8 cases had an outcome categorized as life-threatening; 20 cases resulted in death; 2 resulted in disability; and 74 resulted in hospitalization. A higher proportion of cases involving younger patients were categorized under the reaction group "neoplasms benign, malignant and unspecified" (16% vs. 2%; p<0.01), and older patients had a greater incidence of infectious complications compared with their younger counterparts, though this was marginally significant (40% vs. 23%; p=0.05). The proportion of cases resulting in hospitalization was significantly higher in the ≥60 age group as compared to the <60 age group (79% vs. 44%; p <0.01). Adverse reactions that were common in clinical trials, such as fatigue, pyrexia, headache, peripheral neuropathy, upper respiratory tract infection, hypothyroidism, diarrhea, nausea and vomiting, did not show any significant associations by age group (all p values >0.05).
Conclusions: Although elderly patients comprise 20% of the HL patient population in the US, our post-marketing analysis indicates that AEs in this subgroup account for more than 40% of the total. This suggests that elderly HL patients experience a disproportional number of AEs compared to younger HL patients. While the types of AEs reported in post-marketing cases generally paralleled those observed in clinical trials of HL patients receiving NIVO or PEMBRO, hospitalizations and infections were more common in the elderly group. These differences in the adverse reactions and safety outcomes associated with PD-1 blockade therapy in HL patients may help inform clinical care and monitoring for AEs. Despite the inherent limitations of this study, our findings complement clinical trial safety data and provide insight into real-world trends in reported safety signals that merit further study.
Disclosures
Zettler: Cardinal Health: Employment. Nabhan:Aptitude Health: Employment. Gajra:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.
Adverse Events Following Administration of Anti-CTLA4 Antibody Ipilimumab
