Real-World Outcomes in Patients with Transformed Follicular Lymphoma Treated with CD19-Targeting CAR-T Therapy

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4888-4888
• Main Authors: Rivas-Delgado, Alfredo, Luttwak, Efrat, Drill, Esther, Goldstein, Ilan, Landego, Ivan, Alarcon Tomas, Ana, Parascondola, Allison, Saldia, Amethyst, Caron, Philip, Dahi, Parastoo B., Epstein-Peterson, Zachary D., Falchi, Lorenzo, Hamlin, Paul A., Johnson, William, Kumar, Anita, Lin, Richard J., Lue, Jennifer Kimberly, Owens, Colette, Noy, Ariela, Scordo, Michael, Dogan, Ahmet, Seshan, Venkatraman, Zelenetz, Andrew D., Perales, Miguel-Angel, Shouval, Roni, Palomba, Maria Lia, Shah, Gunjan L., Salles, Gilles
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-187379

INTRODUCTION. CD19-targeting CAR-T cell therapy has changed the treatment landscape of refractory/relapsed large B cell lymphoma, including transformed from FL (tFL). Axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel) are now FDA-approved for the treatment of tFL, but limited data are available on their clinical activity in patients (pts) with tFL since outcomes in those pts were not separately reported in registrational studies. Here, we report a single center's experience with CD19-directed CAR-T cell therapy in pts with tFL. METHODS. We performed a retrospective analysis of 54 pts with tFL treated with CAR-T cell therapy from January 2018 to December 2022. Pathological evidence of histologic transformation (HT) was confirmed. The main clinical-biological characteristics of the pts were extracted from the electronic medical records. Cytokine release syndrome (CRS) and neurotoxicity were graded according to ASTCT guidelines. Progression-free (PFS) and overall survival (OS) were measured from the time of CAR-T cell infusion; PFS events were death, relapse, and disease progression. RESULTS. Within our cohort of patients with tFL, the median age was 67 years (range 42-81), 65% were male and 77% had stage III-IV disease. Eight of the pts (15%) had an ECOG Performance Status (ECOG-PS) ≥2. Median time to transformation was 27 months from original FL diagnosis (range 0 to 223), including 6 cases with composite lymphoma (FL + aggressive histology) and 4 with synchronous transformation. Twenty percent presented with high-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements. Using Hans' algorithm, 85% (44/52) were identified as a germinal center B-cell origin (GCB). In 22 cases, targeted sequencing using the MSK-IMPACT panel was performed at the time of HT or prior to CAR-T. TP53 mutation/deletion was present in 50% of the cases (Figure 1). Pts received a median of 3 (range 1-9) prior lines of therapy including those for FL, and 9 pts (17%) had undergone prior autologous stem cell transplantation (SCT). Thirty-four pts (63%) were refractory to the last therapy, including 29 pts (53.7%) with primary refractory disease after HT. Forty-one pts (76%) received bridging therapy. Seventy-two percent of pts received axi-cel, 19% tisa-cel, and 9% liso-cel. CRS of any grade was seen in 43 (80%) pts with grade >3 in 3 (6%). Neurologic toxicity of any grade was observed in 20 (37%) pts with grade >3 in