Estimating and Projecting the Number of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) By Treatment Lines in the United States

Introduction

Treatment landscape in DLBCL has significantly evolved in the past decade. It is important to quantify and understand the risk groups in DLBCL that represent unmet needs. Hence, we developed a dynamic epidemiology model to estimate and project the annual numbers of adult patients with DLBCL in the first-line (1L), second-line (2L), and third-line (3L) settings from 2024 to 2028 in the US.

Methods

The model estimated the annual incidence of DLBCL using the US population data and incidence rates from the Surveillance, Epidemiology, and End Results Program. A proportion of newly diagnosed DLBCL patients would receive 1L treatments, including rituximab-based chemoimmunotherapies (CIT). Patients with an International Prognostic Index (IPI) score of 2 or higher could receive polatuzumab-based combination and emerging therapies that might be approved after 2024. Annual patient counts in the 1L setting were estimated overall and stratified by IPI scores. Based on time-to-next-treatment (TTNT) and overall survival (OS) of 1L treatments, a proportion of 1L patients progressed and received 2L treatments. Second-line treatments included high-dose chemotherapy + transplantation, chimeric antigen receptor T-cell (CAR-T) therapies, tafasitamab + lenalidomide, polatuzumab-based combinations, bispecific antibodies, other CIT, and emerging therapies that might be approved after 2024. Patients would receive 2L treatments based on eligibility for transplantation and CAR-T if they progressed within 12 months (mo) after 1L treatment initiation; or based on eligibility for transplantation if they progressed after 12 mo. Annual patient counts in the 2L setting were estimated overall and stratified by progression time (≤12 mo vs. >12 mo), eligibility for transplantation, and eligibility for CAR-T therapies. Based on the TTNT and OS of 2L treatments, a proportion of patients progressed and received 3L treatments. Annual patient counts in the 3L setting were estimated overall and for a subgroup receiving prior CD19-directed CAR-T therapies. The TTNT and OS for existing regimens in the 1L and 2L settings were estimated based on the literature, whereas assumptions were made for emerging therapies. Market share for each regimen was derived from market research and assumptions. Sensitivity analysis was conducted by varying the proportion of patients eligible for transplantation in the 2L setting (base-case: 33% transplant eligible and 67% transplant ineligible; sensitivity analysis: 50% transplant eligible and 50% transplant ineligible).

Results

In 2024, it was estimated that 29,400 adult patients with DLBCL would receive 1L treatments, comprising 18,228 (62%) with IPI 2+, 10,584 (36%) with IPI 3+, and 4,116 (14%) with IPI 4-5. Moreover, 8,364 patients would receive 2L treatments, including 4,547 (54%) who progressed ≤12 mo and 3,817 (46%) >12 mo following 1L treatment initiation. Among those who progressed ≤12 mo, 1,440 patients were both transplant- and CAR-T-eligible; 76 were transplant-eligible but CAR-T-ineligible; 1,743 were transplant-ineligible but CAR-T-eligible; and 1,288 were transplant- and CAR-T ineligible. Among those who progressed >12 mo, 1,272 were transplant-eligible and 2,544 were transplant-ineligible. Lastly, 3,671 patients would receive 3L treatments, including 348 who received prior CD19-directed CAR-T therapies. A subgroup analysis indicated that about two-thirds of adult patients in each treatment line aged 65 years or older. In 2028, the projected annual numbers of patients in the 1L, 2L, and 3L settings were expected to increase compared to 2024 (2028 counts: 31,409, 8,519, and 3,734, respectively). In the sensitivity analysis, the annual numbers of patients who would receive 1L, 2L, and 3L treatments were 29,400, 8,364, and 4,029, respectively, in 2024 and were projected to increase over time.

Conclusions

We projected that the annual numbers of DLBCL patients are expected to increase from 2024 to 2028 in the 1L, 2L, and 3L settings. The results also informed the sizes of DLBCL patients by risk group, as well as subgroups with unmet need (limited treatment options), providing an opportunity for the development of novel regimens to improve the outcomes of these patients.

Lu:Janssen Scientific Affairs: Current Employment, Current equity holder in publicly-traded company. Bokun:Janssen US Medical Affairs: Current Employment, Current equity holder in publicly-traded company. Yang:Analysis Group, Inc., Beijing, China: Current Employment, Other: I am an employee of Analysis Group, Inc.; Analysis Group, Inc. received research funding from Johnson & Johnson.. Wang:Analysis Group, Inc.: Current Employment, Other: I am an employee of Analysis Group, which received funding from study sponsors for conducting research projects.. Chen:Analysis Group, Inc., Beijing, China: Current Employment, Other: I am an employee of Analysis Group, Inc.; Analysis Group, Inc. received research funding from Johnson & Johnson.. Wang:Analysis Group, Inc., Beijing, China: Current Employment, Other: I am an employee of Analysis Group, Inc.; Analysis Group, Inc. received research funding from Johnson & Johnson.. Epperla:BeiGene: Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Speakers Bureau; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Research Funding; AstraZeneca: Research Funding.