Mortality trends in patients with mantle cell lymphoma with or without a COVID-19 diagnosis

Abstract Introduction: Mantle cell lymphoma (MCL) is a rare, aggressive non-Hodgkin lymphoma (NHL) that accounts for 5‒7% of all lymphomas. In patients with B-cell NHL, COVID-19 mortality was a concern early in the pandemic when access to vaccines and supportive treatments was limited, though COVID-19 mortality rates generally decreased over time. Data on COVID-19 and MCL are limited; multiple clinical trials enrolled patients with MCL during the pandemic, but interpreting results can be challenging without knowledge of COVID-19 impact in these patients. This study aims to describe trends in mortality over time and specific patient attributes associated with death in patients with MCL with or without a COVID-19 diagnosis. Methods: A retrospective cohort study used Optum CDM data in patients with MCL between 12/1/2019 and 6/30/2024; index date was defined as the later of first MCL diagnosis date or 12/1/2019. COVID-19 vaccination status was based on vaccination claim records; time to vaccination was defined as the time from the date of first vaccine approval by the FDA (12/11/2020) to the date of first COVID-19 vaccination. Annualized all-cause mortality rate (AMR) was defined as total number of deaths per total number of patient-years and was calculated by COVID-19 diagnosis cohorts and by COVID-19 vaccination status. AMR was calculated for the pre-vaccine period (12/1/2019–11/30/2020) and 4 time periods thereafter (12/1/2020–6/30/2024). Results: A total of 1527 patients were included (≥1 COVID-19 diagnosis, n=349; no COVID-19 diagnosis, n=1178): median age 73 and 72 years (with and without COVID-19 diagnosis, respectively), age ≤65 years (22.6% and 28.4%), age 66‒75 years (44.7% and 42.8%), age ≥76 years (32.7% and 28.8%), male (64.5% and 66.1%), and mean Charlson Comorbidity Index (2.97 and 2.86). For patients with MCL and COVID-19 diagnosis, AMR decreased over time during the study (from a peak of 88.4% in the pre-vaccine period, to 41.7% in the immediate post-vaccine period [12/1/2020–11/30/2021], to 20.7% at end of study period [12/1/2023–6/30/2024]). For patients without a COVID-19 diagnosis, AMR remained steady throughout the study period (16.4% pre-vaccine; 12.5–17.4% [post-vaccine periods]). In patients with COVID-19 diagnosis, AMR increased with older age (33.7% in patients ≥76 years vs 10.4% in patients ≤65 years), no vaccination (40.2% vs 11.8% for vaccinated patients), Medicare Advantage (30.3% vs 5.6% with commercial plan; likely age-related), and no prior stem cell transplantation (SCT; 27.9% vs 13.2% in patients with prior SCT). Sex, race/ethnicity, region and time to first vaccine dose did not seem to impact AMR. Conclusions: This retrospective database analysis demonstrated a trend of decreased all-cause mortality over time among patients with MCL and a COVID-19 diagnosis, reflecting similar trends in the general population as access to multiple vaccine options and supportive treatments improved. The most prominent factors associated with death in patients with MCL and COVID-19 diagnosis were older age, no vaccination, and no prior SCT. Study limitations include those inherent to claims data, sample size, and inability to detail cause of death.