A Retrospective Analysis of US Commercial and Medicare Closed-Claims Databases to Evaluate Real-World Characteristics and Treatment Patterns of Patients with Diffuse Large B-Cell Lymphoma (2017-2023)

Introduction:ECHELON-3, a phase 3 randomized-controlled trial, compared brentuximab vedotin (BV) and placebo, both administered with lenalidomide and rituximab, in pts with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) previously treated with ≥2 lines of therapy (LOT). Pts treated with BV had a statistically significant 37% reduction in the risk of death (hazard ratio, 0.629; 95% CI, 0.445-0.891; P=0.0085), regardless of detectable CD30 expression (Kim et al, ASCO 2024; Abstract LBA7005). In contrast with ECHELON 3, many studies evaluating the treatment of R/R DLBCL are single-arm trials. As the treatment of R/R DLBCL is evolving, this study determined how R/R DLBCL is treated, and the role of rituximab, lenalidomide, and CAR T-cell therapy as later LOT, in a contemporary R/R DLBCL population in the US.

Methods:Claims from the MarketScan® Commercial Claims and Encounters and Medicare Databases were retrospectively analyzed for pts aged ≥18 yrs with 1 inpatient or 2 outpatient (≥30 days but ≤365 days apart) DLBCL claims (ICD-9 200.7x or ICD-10 C83.3x) who initiated first-line (1L) therapy between January 2017-June 2023 and had ≥6 mo continuous enrollment prior to DLBCL diagnosis (ie, baseline period). Pts were excluded if diagnosed with another hematologic or a solid malignancy during the baseline period. Baseline characteristics and treatment patterns were assessed. Treatment patterns were hierarchically classified as rituximab-, lenalidomide-, polatuzumab-, and tafasitamab-based therapies; CAR T-cell therapy; CD20/CD3 bispecific antibodies; loncastuximab-, selinexor-, BV-, and bendamustine-based therapies; and other (ie, therapy not specified in the hierarchy). Following initial DLBCL diagnosis, the first anticancer treatment claim was considered 1L therapy. Therapies initiated within the first 28 days of treatment cycle 1 were deemed the same LOT. A LOT ended at the earliest of switch (new DLBCL treatment ≥29 days after LOT start), discontinuation (>90-day gap in all treatment), or end of follow-up. Pts were followed until the first of either the end of enrollment or end of data availability. Time to next treatment (TTNT) was defined as the time from the start of the former treatment to the start of a new treatment. Continuous variables were summarized using mean and standard deviation (SD) and median and interquartile range (IQR). Categorical variables were summarized by counts and percentages.

Results:In total, 3552 pts received 1L therapy and were followed for a median (IQR) duration of 15 (8-30) mo. Median (IQR) pt age at DLBCL diagnosis was 59 (50-65) yrs, 56.9% of pts were men. The baseline median (IQR) Charlson Comorbidity Index score was 2 (2-4). In 1L, 90.0% of pts (n=3196) received a rituximab-based therapy (64 different regimens identified). Of those receiving 1L therapy, 19.7% (n=699) received second-line (2L) therapy; the median (IQR) TTNT was 6 (3-10) mo. In 2L, 68.0% of pts received a rituximab-based therapy (60 different regimens identified), 4.9% received a lenalidomide-based therapy, 2.6% received CAR T-cell therapy, and 18.7% received an “other” therapy. Of those receiving 2L therapy, 35.5% (n=248) received third-line (3L) therapy; the median (IQR) TTNT was 4 (2-7) mo. In 3L, 54.8% of pts received a rituximab-based therapy (31 different regimens identified), 7.3% received a lenalidomide-based therapy, 3.2% received CAR T-cell therapy, and 25.0% received an “other” therapy. Of those receiving 3L therapy, 39.9% (n=99) received fourth-line (4L) therapy; the median (IQR) TTNT was 3 (2-6) mo. In 4L, 50.5% of pts received a rituximab-based therapy (11 different regimens identified), 7.1% received a lenalidomide-based therapy, 6.1% received CAR T-cell therapy, and 22.2% received an “other” therapy.

Conclusions: The treatment landscape for R/R DLBCL is evolving. Results from this retrospective contemporary analysis of US real-world data showed heterogeneity in treatments administered with a lack of standard of care in the 3L/4L setting. Most pts received rituximab-based treatment as 2L or later-line therapy; few patients received CAR T-cell therapy highlighting a need for new regimens that demonstrate clinical benefit and improved survival, while also being more deliverable and acceptable to the community.

Phillips:Abbvie: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; ADCT: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Eli Lilly and Company: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy; Xencor: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees. Zhou:Pfizer: Consultancy, Research Funding; Genesis: Current Employment. Gutierrez:Genesis: Current Employment; Pfizer: Consultancy, Research Funding. Shao:Pfizer: Consultancy, Research Funding; Genesis: Current Employment. Boyd:Novartis: Consultancy, Research Funding; Genesis Research Group: Current Employment. Noshad:Genesis Research Group: Current Employment; Novartis: Consultancy, Research Funding. Hohlbauch:Pfizer: Consultancy, Research Funding; Genesis: Current Employment. Liu:Pfizer: Current Employment, Current holder of stock options in a privately-held company. Repetny:Pfizer: Current Employment, Current holder of stock options in a privately-held company. Fanale:Seagen: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Pfizer: Current Employment, Current holder of stock options in a privately-held company. Mitchell:Pfizer: Current Employment, Current holder of stock options in a privately-held company. Burke:Genentech/Roche: Consultancy; SeaGen: Consultancy; BeiGene: Consultancy; Kymera: Consultancy; Bristol Myers Squibb: Consultancy; Genmab: Consultancy; Foresight Diagnostics: Consultancy; AstraZeneca: Consultancy; Abbvie: Consultancy; Nurix: Consultancy; Adaptive Biotechnologies: Consultancy; Novartis: Consultancy; Eli Lilly and Company: Honoraria, Other: Food/Beverage ; Regeneron: Consultancy.