Safety and efficacy outcomes with three CD19-directed CAR T-cell therapies in Italy were concordant with other real-world data with CAR T-cell therapy in patients with B-cell malignancies, according to data from a single-center experience presented during the 51st Annual EBMT Meeting.1
Among all patients (n = 44), cytokine release syndrome (CRS) occurred in 95% (n = 42) of cases, all of which were characterized as grade 1 or 2 events. Immune effector cell–associated neurotoxicity syndrome occurred in 9% (n = 4) of patients and was grade 1/2 in 1% of cases and grade 3/4 in 3%. Hemophagocytic lymphohistiocytosis occurred in 2% (n = 1) of patients.
Tocilizumab (Actemra) was used in 34% (n = 15) of patients, and the median number of doses was 2 (range, 1-4). Steroids and anakinra were used in 18% (n = 8) and 2% (n = 1) of cases, respectively.
“Our results are concordant with other reports of real-life experiences with CAR [T-cell therapy] and support the use of CAR [T-cell therapy] with reversible and manageable toxicities,” lead study author, Giorgia Battipaglia, MD, of Federico II University of Naples in Italy, and coauthors wrote in the poster.
CD19-directed CAR T-cell therapy has revolutionized the treatment paradigm for patients with B-cell malignancies despite their risk for CRS and neurologic events. Real-world evidence has shown that such adverse effects do affect patients in the clinic but at a lower severity.
To augment current real-world data, investigators from the Federico II University of Naples conducted a single-center study that evaluated the outcomes of patients with B-cell malignancies who received commercially available CD19-directed CAR T-cell therapy between October 2021 and November 2024.
Patient eligibility was assessed in accordance with the Agenzia Italiana del Farmaco criteria.
A total of 92 patients were screened, 33 of whom did not meet eligibility criteria due to recent thrombosis (n = 2), cardiac comorbidity (n = 3), ECOG performance status of 3 (n = 2), history of epilepsy (n = 1), CD19-negative disease (n = 1), unknown CD19 status after tafasitamab-cxix (Monjuvi; n = 1), CAR T-cell therapy not being indicated (n = 6), central nervous system positivity (n = 2), and active infection (n = 3). Other reasons for ineligibility were a move to another CAR T-cell therapy center (n = 4), receipt of alternative treatment (n = 2), and missing reason (n = 6).
A total of 59 patients (64%) underwent apheresis. The breakdown of distributed products was as follows: axicabtagene ciloleucel (axi-cel; Yescarta) for diffuse large B-cell lymphoma (DLBCL) in the third line (27%), axi-cel for DLBCL in the second line (17%), axi-cel for primary mediastinal B-cell lymphoma (PMBCL; 5%), axi-cel for follicular lymphoma (8%), brexucabtagene autoleucel (brexu-cel; Tecartus) for acute lymphoblastic leukemia (ALL; 5%), brexu-cel for mantle cell lymphoma (MCL; 12%), tisagenlecleucel (tisa-cel; Kymriah) for DLBCL (22%), tisa-cel for follicular lymphoma (8%), and tisa-cel for ALL (2%).
A total of 58% (n = 34) of patients received bridging therapy prior to CAR T-cell therapy infusion. Bridging therapies for patients with DLBCL included rituximab (Rituxan) plus polatuzumab vedotin-piiq (Polivy) and bendamustine (n = 11); rituximab plus polatuzumab (n = 4); rituximab plus lenalidomide (Revlimid; n = 3); radiotherapy (n = 1); rituximab plus gemcitabine and oxaliplatin (n = 3); and rituximab plus ICE (n = 1). Patients with PMBCL received brentuximab vedotin (Adcetris) plus nivolumab (Opdivo; n = 2). Patients with MCL received a BTK inhibitor (n = 3) or rituximab plus venetoclax (Venclexta; n = 1). Patients with ALL received either intrathecal chemotherapy (n = 1), vincristine (n = 1), a TKI (n = 1), or inotuzumab ozogamicin (n = 1; Besponsa). One patient with follicular lymphoma received bendamustine (n = 1).
The results indicated that 19% (n = 11) of patients were not able to undergo infusion due to disease progression/sudden death.
A total of 76% (n = 45) patients underwent infusion. One patient with follicular lymphoma and progressive disease died 2 days after infusion resulting from a fatal post-traumatic hemorrhage and was removed from the post-infusion analysis.
Among all patients included in the analysis (n = 44), most were female (53%). The median age was 58 years (range, 22-83), and 9% of patients received an out-of-specification product. The median manufacturing time was 28 days (range, 16-54), and the median time from product shipment to infusion was 33 days (range, 5-122). Disease status before infusion was recorded as stable disease (44%), progressive disease (15%), partial response (34%), and complete response (7%). The median duration of hospitalization was 19 days (range, 9-32).
At last follow-up ten patients had died due to disease relapse (n = 8), which included 2 CD19-negative relapses, the development of a TP53-mutated myelodysplastic syndrome (n = 1), and an unknown cause (n = 1).
With a median follow-up of 7 months (range, 1-31), the 6-month progression-free survival and overall survival rates were 81% (±7) and 84% (±6), respectively.
The study authors noted in conclusion that no patients required transfer to the intensive care unit.
Disclosures: No disclosures were listed.
Reference
Battipaglia G, Andretta C, Correale P, et al. Outcomes after CD19-directed chimeric antigen receptor T cells for B-cell malignancies: a single center experience. Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025; Florence, Italy. Abstract A126.