Bispecific antibody vs non-bispecific antibody systemic therapy as immediate next line treatment after chimeric antigen receptor T-cell (CART) failure in large B-cell lymphoma
Year: 2025
Type: conference-abstract
Abstract: Background For patients with large B-cell lymphoma (LBCL) who relapse after CART, optimal next line therapy is unknown. Bispecific antibodies (BsAbs) redirect T cells to target malignant B cells and are commonly used post-CART. Real-world patient selection and comparative efficacy for BsAbs vs other regimens after CART failure is limited. We evaluated outcomes of BsAb- vs non-BsAb-based salvage therapies following CART failure. Methods Among 935 relapsed/refractory (R/R) LBCL patients (pts) treated with CART between 2015-2024 across 15 academic institutions, pts with CART failure were grouped according to BsAb-based vs non-BsAb salvage therapy. Differences between variables were evaluated with Wilcoxon rank-sum test and pooled t-test (two-sided P<.05). Time-to-event curves were established by Kaplan-Meier method. Cox multivariable regression analysis (MVA) evaluated clinical impact. Results In 490 pts with CART failure, 311 received systemic salvage therapy. Median age was 59 years (range 19–85), 62% were male, 78% were Caucasian, and histology included de novo DLBCL (72%), transformed follicular lymphoma (13%) or other LBCLs (15%). Most common CART product was axi-cel (56%), followed by tisa-cel (21%), liso-cel (22%), and others (1%). 73 pts received BsAbs, with BsAb monotherapy (B-M) in 60 pts and BsAb + targeted therapy (B+T) in 13 pts. Non-BsAb regimens (n=238) included chemoimmunotherapy (CIT, n=45), lenalidomide +/- tafasitamab (len +/-taf, n=75), polatuzumab-bendamustine-rituximab (pola-BR; n=48), checkpoint inhibitors (CPI, n=25), loncastuximab (lonca, n=7) or other targeted therapies (TT, n=38). Baseline characteristics were balanced between the B-M and non-BsAb groups, including age, sex, cell of origin, double-hit lymphoma (DHL), primary refractory disease to frontline CIT (PRD), prior autologous transplant, prior bendamustine, and time to salvage <90 days post–CAR-T. However, B-M pts had a higher rate of EN disease as compared to non-BsAb pts (86% vs 70%, p=0.01). Pts who received CIT were typically younger (p<0.05) with de novoDLBCL (p=0.03) compared to all other treatment groups with the exception of pts receiving CPI. For B-M vs non-BsAb, median duration of follow-up was 12.5 vs 40.8 mo. Median PFS was 4.7 vs 2.4 mo (p=0.057); mOS was similar, 8.9 vs 9.9 mo (p=0.7). Comparing across all treatment regimens: mPFS (in mo) was 4.7 (B-M), 7.4 (B+T), 1.1 (CIT), 2.7 (len +/- taf), 4.6 (pola-BR), 1.8 (CPI), 1.4 (lonca), and 1.9 mo (TT; p=0.003). Median OS (in mo) was 8.9 (B-M), 10 (B+T), 5.4 (CIT), 12.5 (len +/- taf), 10.7 (pola-BR), 9.9 (CPI), 18.7 (lonca), and 8.5 mo (TT; p=0.8). In PRD, longest mPFS was associated with B+T (7.4 mo), pola-BR (3.6 mo), and B-M (3.2 mo) as compared to len +/- taf, lonca and CPI (mPFS range 0.5-2.7 mo, p<0.001) with no difference in mOS (p=0.6). In DHL, OS and PFS did not differ by regimen (mPFS range 0.9-13.6 mo, p=0.3; mOS range 0.9-4.8 mo, p=0.14). With relapse >180 days post-CART (n=91): B-M vs B+T vs len +/- taf performed best for mPFS (NR vs 16.3 vs 22.4 mo respectively, p=0.005). With relapse <180 days post-CART (n=211): mPFS (in mo) from highest to lowest was 7.4 (B+T), 3.8 (pola-BR), 2.6 (B-M), 1.9 (len +/- taf), 1.8 (CPI), 1.4 (TT) and 1 mo (either CIT or lonca, p=0.03). With relapse >180 days post-CART (n=91), B-M vs B+T vs len +/- taf performed best (mPFS NR vs 16.3 vs 22.4 mo respectively, p=0.005). For mOS for this subset was not different by regimen (range 4.5-9.4 mo, p=0.8). In MVA, no regimen offered PFS or OS benefit post-CART failure over B-M. However, pts who received CIT [HR=2.0 (95% CI 1.1-3.7)], CPI [HR=2.0 (95% CI 1.2-3.4)] or lonca [HR=4.4 (95% CI 1.7-11.6)] had worse PFS (p=0.003). PRD and relapse <180 days post-CART were independently associated with decreased mPFS (p<0.007) and mOS (p<0.009). Conclusion In pts with R/R LBCL post-CART failure, BsAb-based salvage demonstrated superior mPFS without significant OS benefit compared to most non-BsAb therapies, particularly in late relapse. Survival with BsAb and non-BsAb treatments within 6 months of CART were diminished, suggesting that timing of relapse influences effectiveness of salvage regimens. Treatment-era bias may affect results, as many non-BsAb pts were potentially treated before BsAb FDA approval, but our results support integration of BsAbs in the post-CART setting. Prospective validation is warranted to define optimal sequencing of BsAbs and other treatment options in post-CART treatment paradigms.
Source: Blood
Authors: Kyle Miyazaki, Natalie Grover, Colin Thomas, Yun Kyoung Tiger, Ari Pelcovits, Matthew Cortese, James Davis, Adam Kidwell, Tamara Moyo, Lindsey Fitzgerald, Jonathon Cohen, Megan Melody, Vaishalee Kenkre, Megan Herr, Thomas Ollila, Geoffrey Shouse, Daniel Antonio, Deborah Stephens, Nirav Shah, Nour Nassour, Omar Elghawy, Jonathan Moreira, Adit Dharia, Salmaan Mubeen, Shuo Ma, Jane Winter, Leo Gordon, Brian Hess, Narendranath Epperla, Reem Karmali
Institutions: Northwestern University, University of North Carolina at Chapel Hill, University of Pennsylvania, Rutgers, The State University of New Jersey, Rutgers Cancer Institute, Brown University, Roswell Park Comprehensive Cancer Center, Medical University of South Carolina, MUSC Hollings Cancer Center, Medical College of Wisconsin, Medical College of Wisconsin Cancer Center, Levine Cancer Institute, University of Utah, Huntsman Cancer Institute, Emory University, Winship Cancer Institute, Tampa General Hospital, University of Wisconsin–Madison, University of Wisconsin Carbone Cancer Center, City Of Hope National Medical Center, City of Hope, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, University at Buffalo, State University of New York, University of South Florida, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7108469995
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