Impact of Salvage and Bridging Therapy in Adult Patients with Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL) Referred for Anti-CD19 CAR T-Cell Therapy: An Intention to Treat Analysis

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4875-4875
• Main Authors: Ortiz-Maldonado, Valentin, Martinez-Cibrian, Nuria, Del Campo Balguerías, Gonzalo, Español-Rego, Marta, Navarro, Sergio, Brillembourg, Helena, Alserawan, Leticia, Castella, Maria, Benitez-Ribas, Daniel, Magnano, Laura, Correa, Juan Gonzalo, Rivero, Andrea, Mozas, Pablo, Oliver-Caldes, Aina, Gine, Eva, Rodríguez-Lobato, Luis Gerardo, Martínez-Roca, Alexandra, Montoro-Lorite, Mercedes, Ayora, Pilar, Fernández de Larrea, Carlos, Pascal, Mariona, Esteve Reyner, Jordi, Urbano-Ispizua, Alvaro, Juan, Manel, Delgado, Julio
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-187226

Background: Prognosis of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) is poor, particularly after allogeneic hematopoietic cell transplantation (alloHCT). In this setting, several CAR T-cell products targeting CD19 (CART19) have been able to achieve complete response (CR) rates of 70 to 90%. However, a significant proportion of these patients still relapse. Several studies focus on the effect of the CART19 product on efficacy, however, information on how salvage therapy (ST) and bridging therapy (BT) can modulate the outcomes of CART19 therapy is scarce. Methods: We report the outcomes of all adult patients with R/R B-ALL intended for treatment (aphaeresis performed) with available CART19 products in a single institution from Jul 2017 to Jul 2023. This includes patients intended to receive the academic varnimcabtagene autoleucel (var-cel) in the CART19-BE-01 trial and the consecutive compassionate use and hospital exemption programs, as well as with commercially available tisagenleuceucel (tisa-cel). Lymphodepletion was performed with fludarabine (90 or 120 mg/m 2) and cyclophosphamide (900 or 1000 mg/m 2), followed by the infusion var-cel or tisa-cel, respectively. We analyzed all ST (treatment administered after last relapse before CART19-apheresis) and BT (treatment administered after apheresis and before CART19 infusion) performed, and analyzed the impact of BT on PFS and OS after apheresis. Results: A total of 74 adult B-ALL patients underwent leukapheresis and CART19 (var-cel/tisa-cel) production. At screening patients had a median age of 34 years (19-78), 45% were females, with a median of 3 prior lines of therapy (2-7) including inotuzumab (69%), blinatumomab (27%) and allo-HCT (84%). After last relapse, 92% of patients received ST with a median of 1 (0-3) treatment line, including inotuzumab (48%), high-dose chemotherapy (28%), low-dose chemotherapy (21%), TKIs (12%), blinatumomab (9%), radiotherapy (7%) and DLIs (4%). The overall response to ST prior apheresis was MRD-negative CR (28%), MRD-positive CR (22%), partial response (4%) and progressive disease (PD) in 46%. After apheresis was secured, BT was performed in 76% of patients with a median of 1 (0-2) bridging line, including low-dose chemotherapy (44%), intrathecal therapy (23%), high-dose chemotherapy (15%), TKIs (15%), inotuzumab (14%), radiotherapy (3.5%), blinatumomab (1.8%) and DLIs (1.8%). BT was not administered in 24% (8/74) of patients mainly due to morphologi