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). The results showed a statistically and clinically 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, in pts treated with BV (Kim et al, ASCO 2024; Abstract LBA7005). In order to better understand the recent, evolving treatment landscape for R/R DLBCL, and in particular the role of rituximab, lenalidomide, and CAR T-cell therapy in later LOT, we analyzed US claims data.
Methods: Claims from the nationally representative US Symphony Health Solutions database were retrospectively analyzed for pts aged ≥18 yrs with 1 inpatient or 2 outpatient (≥30 but ≤365 days apart) DLBCL claims (ICD-9 200.7x or ICD-10 C83.3x) who initiated first-line (1L) therapy between January 2017-May 2024 and had ≥6 months' continuous enrollment prior to DLBCL diagnosis (ie, baseline period). Pts with any other cancer during the baseline period were excluded. Baseline pt characteristics and treatment patterns were assessed. Treatment patterns were classified using this hierarchy: 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 hierarchy). The first anticancer treatment claim following initial DLBCL diagnosis was considered 1L therapy. All therapies initiated within the first 28 days of treatment cycle 1 were considered 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/or median and interquartile range (IQR). Categorical variables were summarized by counts and percentages.
Results:In total, 49,370 pts received 1L therapy and were followed for a median (IQR) duration of 35 (15-59) months. Median (IQR) pt age at DLBCL diagnosis was 68 (58-74) yrs; 54.9% of pts were men, and 57.8% were Caucasian. Baseline median (IQR) Charlson Comorbidity Index score was 2 (2-3). In 1L, 87.9% of pts (n=43,397) received a rituximab-based therapy (143 different regimens identified). Among those receiving 1L therapy, 21.1% (n=10,430) received second-line (2L) therapy; median (IQR) TTNT was 7 (3-14) months. In 2L, 68.1% of pts received a rituximab-based therapy (125 different regimens identified), 3.9% received a lenalidomide-based therapy, 1.2% received CAR T-cell therapy, and 18.8% received therapies classified as other. Of those receiving 2L therapy, 32.7% (n=3410) received third-line (3L) therapy; the median (IQR) TTNT was 5 (3-10) months. In 3L, 58.7% of pts received a rituximab-based therapy (65 regimens identified), 5.0% received a lenalidomide-based therapy, 1.8% received CAR T-cell therapy, and 21.5% received therapies classified as other. Among those receiving 3L therapy, 37.3% (n=1272) received fourth-line (4L) therapy; the median (IQR) TTNT was 5 (3-8) months. Of those receiving 4L therapy, 57.7% received a rituximab-based therapy (23 different regimens identified), 4.7% received a lenalidomide-based therapy, 2.6% received CAR T-cell therapy, and 17.9% received therapies classified as other.
Conclusions:The treatment landscape for R/R DLBCL is evolving. Results from this contemporary real-world analysis demonstrate heterogeneity in treatments administered with a lack of standard of care in the 3L/4L setting. Most pts with R/R DLBCL received rituximab-based second or later-line therapies with numerous, different, rituximab-based regimens administered. Few patients received CAR T-cell therapy. These results highlight a need for more efficacious, evidence-based therapies that improve overall survival in pts with R/R DLBCL, while also being more deliverable and acceptable to the community.
Burke:Abbvie: Consultancy; Foresight Diagnostics: Consultancy; AstraZeneca: Consultancy; Adaptive Biotechnologies: Consultancy; Genmab: Consultancy; Genentech/Roche: Consultancy; Bristol Myers Squibb: Consultancy; Kymera: Consultancy; Regeneron: Consultancy; SeaGen: Consultancy; BeiGene: Consultancy; Eli Lilly and Company: Honoraria, Other: Food/Beverage ; Novartis: Consultancy; Nurix: Consultancy. Zhou:Genesis: Current Employment; Pfizer: Consultancy, Research Funding. 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:Genesis: Current Employment; Pfizer: Consultancy, Research Funding. 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. Phillips:Pharmacyclics: Consultancy; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADCT: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Bayer: 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; 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; Xencor: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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