REAL-WORLD SEQUENTIAL USE OF CD19-DIRECTED THERAPIES FOR RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: TAFASITAMAB PRECEDING CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY

Abstract

Objectives: Potential CD19 antigen loss following CD19-directed therapy has raised concerns over sequential use of these therapies, and real-world data are limited. Tafasitamab, a CD19-targeting immunotherapy, combined with lenalidomide, is approved by the US Food and Drug Administration for treatment of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) in adults ineligible for autologous stem cell transplantation. Here, we examine characteristics and outcomes of patients who received tafasitamab for R/R DLBCL preceding CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy in a real-world setting. Material and methods: In this retrospective, multisite, medical chart review study, participating physicians from Cardinal Health's Oncology Provider Extended Network abstracted data from US adults who initiated tafasitamab (with or without lenalidomide) on or after October 21, 2020, for R/R DLBCL outside clinical trial settings. Patients were required to have ≥4 months of follow-up after tafasitamab initiation unless deceased. Initial data collection (February-March 2023) identified 181 eligible patients, and follow-up data were collected approximately 10 months thereafter. Results for patients who received tafasitamab preceding CAR-T therapy were summarized using descriptive statistics. Results: Nine patients (median age at tafasitamab initiation, 63 years; 3 male; 6 White) received tafasitamab and lenalidomide (tafa+len) as a line of therapy immediately preceding CAR-T therapy. Median (Q1-Q3) follow-up time since tafasitamab initiation was 26.1 (18.0-28.0) months and after CAR-T administration was 9.3 (1.9-16.7) months. At tafasitamab initiation, 7 patients had Eastern Cooperative Oncology Group performance status 0-1 and 2 had primary refractory disease. Of the 9 patients, 4 had complete response, 4 had partial response, and 1 had stable disease as best real-world response to tafa+len; all discontinued tafasitamab due to disease progression. Median (Q1-Q3) tafasitamab therapy duration was 11.0 (8.1-14.1) months. Three patients had CD19 testing following tafasitamab discontinuation, and all test results were positive. Median (Q1-Q3) time from tafasitamab discontinuation to CD19 testing was 7 (6-9) days. Among the 9 patients, median (Q1-Q3) time from tafasitamab discontinuation to initiation of CAR-T therapy was 3.2 (2.3-3.6) months. Four patients had complete response, 3 had partial response, and 1 had progressive disease as best real-world response to CAR-T therapy; 1 patient was not evaluable. Discussion: These results suggest that in patients treated with tafasitamab, CD19 expression remains detectable following treatment discontinuation, and disease response can be achieved with subsequent CD19-directed CAR-T therapy. However, this study is limited by small sample size. Conclusion: This small real-world analysis demonstrated disease response to CD19-directed CAR-T therapy and detectable CD19 expression following tafasitamab treatment for R/R DLBCL. Further studies with larger sample sizes are warranted to confirm these findings. Funding: Incyte Corporation.