A Real-world Study of the Effectiveness and Safety of Chimeric Antigen Receptor T-cell Therapy Following Tafasitamab in Patients With Relapsed/refractory Diffuse Large B-cell Lymphoma
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background The expanding landscape of CD19-directed therapies for diffuse large B-cell lymphoma (DLBCL), including tafasitamab (tafa) and chimeric antigen receptor T-cell (CAR-T), is promising for patients (pts). However, there exist theoretical concerns that prior exposure to anti-CD19 therapy may compromise the efficacy of subsequent treatment with CAR-T. Several studies have demonstrated retention of CD19 expression following tafa, with limited evidence on the effectiveness and safety of sequential use of CAR-T post tafa. Aim To assess effectiveness and safety of CAR-T post tafa among adult pts with relapsed/refractory (R/R) DLBCL. Materials and methods A retrospective, US and EU panel-based chart review collected data for adults with R/R DLBCL who received tafa (± lenalidomide) and also subsequent CAR-T (index date) in second-line (2L)/3L/4L. Pts had to have ≥6 months of follow-up post CAR-T (except in the event of death); pts were followed until the start of new anticancer therapy after CAR-T, end of data availability, or death (whichever occurred first). Outcomes included overall response rate to CAR-T (ORR: proportion of pts with physician-assessed complete/partial response [CR/PR]), proportion of pts with cytokine release syndrome (CRS) within 6 weeks and immune effector cell–associated neurotoxicity syndrome (ICANS) within 3 months after CAR-T, and were reported for the overall population, by CAR-T line, and by tafa/CAR-T treatment sequence. Results A total of 338 pt charts (US: 168 [49.7%]; EU: 170 [50.3%]) were abstracted by 145 physicians (US: 73 [50.3%]; EU: 72 [49.7%]). Pts were 66.0% male with median (IQR) age 61.5 (55.1, 67.4) years at CAR-T infusion, 72.8% were primary refractory, and 53.0% had a revised International Prognostic Index score ≥3. CAR-T therapies administered (in 2L [n=37; all pts received tafa as bridging therapy to CAR-T], 3L [n=243], and 4L [n=58]) were axicabtagene ciloleucel (65.1%), lisocabtagene maraleucel (21.9%) and tisagenlecleucel (13.0%) Median (IQR) time from the last tafa dose until CAR-T was 1.2 (0.6-2.3) months; follow-up duration post CAR-T was 7.4 (3.3-10.6) months; and 73.1% of pts were still alive at the time of last contact. Overall, ORR for CAR-T among all pts was 81.1% (CR 58.6%, PR 22.5%). By CAR-T line, ORR was 91.9% (CR 59.5%, PR 32.4%) in 2L, 80.2% (CR 60.1%, PR 20.2%) in 3L, and 77.6% (CR 51.7%, PR 25.9%) in 4L. CRS and ICANS occurred in 30.8% (severe [grade ≥3], 7.4%) and 15.4% (severe [grade ≥3], 3.8%) of all pts, respectively. By line of CAR-T, respective incidences of CRS and ICANS were 24.3% (severe [grade ≥3], 5.4%) and 10.8% (all non-severe) in 2L, 29.6% (severe [grade ≥3], 7.4%) and 14.4% (severe [grade ≥3], 4.5%) in 3L, and 39.7% (severe [grade ≥3], 8.6%) and 22.4% (severe [grade ≥3], 3.4%) in 4L. Discussion Findings from this large, global, real-world study demonstrated favorable effectiveness and safety outcomes with CAR-T therapy in pts with R/R DLBCL who were previously treated with tafa. These findings are particularly relevant in the context of the evolving DLBCL treatment landscape, including emerging front-line tafa data and the potential impact of prior tafa exposure on later-line treatment sequencing. Conclusion While these real-world study findings should be interpreted in the context of an observational cohort, they support tafa followed by CAR-T therapy as a viable treatment sequencing strategy in clinical practice. Funding: Incyte Corporation.
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223156536