Introduction: Non-Hodgkin lymphoma (NHL) is the most common hematologic cancer in the US, with an estimated 80,350 new cases in 2025. Diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are aggressive subtypes of NHL, accounting for about 30% (most common) and 3-10% of all NHL cases in the US, respectively. Given major changes in the treatment landscape for DLBCL and MCL, estimating and forecasting the incidence, prevalence, and number of treatment-eligible patients of these two NHL subtypes by line of therapy (LoT) in the US is important for understanding the burden of NHL and identifying unmet need. However, there is a lack of comprehensive and up-to-date forecasted estimates for DLBCL and MCL, with many inconsistencies in the existing literature. The aim of this study was to 1) estimate and forecast the incidence and prevalence of DLBCL and MCL in the US from 2023 to 2032 by applying validated methods, and 2) construct a patient count model to estimate and forecast the number of treatment- eligible patients with DLBCL and MCL by LoT in the US from 2023 to 2032.

Methods: Historical incidence rates of DLBCL and MCL in the US (2017-2022), obtained from Surveillance, Epidemiology, and End Results (SEER) 21 (Nov 2024 submission), were used as the observation timeframe for projections. Data from 2020 was excluded as an outlier due to the impact of Covid-19. A validated joinpoint regression model from our previous work was applied to forecast age- and gender- specific incidence rates from 2023 to 2032. Annual cases were computed by multiplying projected rates and national population estimates from the US Census Bureau, summing across all subgroups for total incidence. For the 20-year prevalence of DLBCL and MCL in the US from 2023 to 2032, a model incorporating incidence, survival, and the likelihood and timing of cure was used for projections. This model included 1) a 52.8% cure rate, 2) the onset of cure beginning 10 years post-diagnosis, and 3) all surviving patients being considered cured by 20 years post-diagnosis. It demonstrated the best goodness-of-fit for DLBCL prevalence in our previous work. A new patient count model incorporating 1) incidence, 2) re-entry patients diagnosed in prior years, and 3) proportion of patients receiving systemic therapy by LoT was developed to estimate the number of treatment eligible patients with DLBCL and MCL by LoT. A literature review of PubMed and Embase (January 2014 - April 2025) was conducted to determine the percentage of 1) re-entry DLBCL and MCL patients by LoT, and 2) watchful waiting MCL patients. The SEER-Medicare linked database (2012-2021) was used to estimate the proportion of DLBCL/MCL patients receiving treatment in 1L, 2L, 3L, and 4L.

Results: Overall, the US incidence for DLBCL is expected to increase by 7% from 28,838 to 30,772 between 2023 and 2032. By age group, the DLBCL incidence is projected to increase by 11% in individuals aged ≥65 years while it is anticipated to decrease by 2% in those aged <65 years. For MCL, the incidence is projected to increase by 6% from 3,377 to 3,589 during the same period. From 2023 to 2032, the projected 20-year prevalence is expected to increase by 20% for DLBCL from 199,368 to 238,862 and by 19% for MCL from 22,946 to 27,208. The number of treatment- eligible patients is projected to increase significantly for DLBCL across all LoT, rising from 33,120 to 35,523 in 1L (7% increase), from 9,243 to 9,976 in 2L (8% increase), from 4,466 to 4,821 in 3L (8% increase), and from 2,163 to 2,335 in 4L (8% increase). For MCL, the number of treatment-eligible patients is anticipated to increase 6% in each LoT: from 3,376 to 3,591 in 1L, from 1,220 to 1,297 in 2L, from 685 to 729 in 3L, and from 379 to 405 in 4L.Conclusions: Using validated methods, a newly developed model, and contemporaneous data, our study showed that the estimated incidence, prevalence, and the number of treatment-eligible DLBCL and MCL patients by LoT are substantial and expected to increase steadily over the next several years. These findings will be valuable for stakeholders in planning, monitoring, and resource allocation to address the growing burden of DLBCL and MCL in the US.

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2025
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