Trends in All-Cause Mortality Rates in Patients with Follicular Lymphoma in the US before and during the COVID-19 Pandemic: A Retrospective Observational Study

Introduction: With the advent of new agents, the overall prognosis of patients with follicular lymphoma (FL) has substantially improved in the last few decades. However, the global COVID-19 pandemic posed a significant challenge for patients with hematologic malignancies, including those undergoing treatment for FL. The pandemic introduced unprecedented excess morbidity and mortality, potentially confounding clinical trial outcomes and impacting real-world assessments of patient health outcomes. COVID-19 infections were the highest at the peak of the pandemic in 2021, coincident with the highly contagious Omicron variant dominating at the time. Due to their advanced age, many patients with FL had a markedly increased risk of COVID-19 mortality. Assessing all-cause mortality rates in the pre- and post-COVID eras in real-world databases can provide insights into the impact of the pandemic on these patients, as COVID-specific mortality reporting was inconsistent. This study aimed to present trends in the mortality rates for patients with FL who initiated treatment before and after January 1, 2020, stratified by age, to address the current gaps in the literature on the impact of COVID-19 on mortality data in patients with FL.

Methods: The COTA-FL Electronic Health Records (EHR) database from 2010 to 2022 was utilized to assess annual crude all-cause mortality rates. All-cause mortality rates were calculated as the number of annual deaths divided by the total number of people at risk in the database in that year. Annual mortality rates (per 1000 persons) were studied from 2016 to 2022 for patients diagnosed with FL between 2010 and 2022. Stratification was performed by diagnosis and treatment initiation in the years before and after 2020 (pre- and post-COVID eras, respectively) and by age groups <65 and 65+ years.

Results: Among 4881 patients in the COTA-FL cohort, 49.0% of patients were 65+, 48.0% were male, and 77.3% were White. Death rates per 1000 persons fell between 2016 and 2019 (30.2 to 26.9) but increased between 2020 to 2022 (31.5 to 47.1). In the treated population, higher mortality rates were observed in recent years, particularly 2021 and 2022 (54.4, 54.3). Patients in the 65+ vs <65 year age groups had higher death rates (65+: 58.0 to 93.3; <65: 14.6 to 31.3) with the highest rates seen in 2021 and 2022. For the 65+ year age group, rates ranged from 61.7 to 93.3 in 2020 to 2022 vs 58.0 to 67.6 in 2016 to 2019. Treated patients had higher rates of death in 2021 and 2022 when stratified by treatment initiation in the post-COVID era vs the pre-COVID era (2020+ treatment initiation: 64.1, 73.6; pre-2020 treatment initiation: 52.3, 48.9).

Conclusion: Mortality rates increased during the years of the COVID-19 pandemic, peaking in 2021 and 2022, coinciding with the Omicron variant. As anticipated, the 65+ year age group and patients initiating new therapy experienced elevated mortality rates compared with patients under 65 years of age and those not initiating new therapies. Thus, COVID-19 substantially reduced survival of patients with FL and could have confounded survival outcomes in clinical trials, especially those conducted during the Omicron variant.