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Obe-cel produced responses and low rates of high-grade CRS and ICANS in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia.
Treatment with obecabtagene autoleucel (obe-cel; Aucatzyl) led to low rates of high-grade cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), along with high response rates, in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), according to data from the phase 1b CATULUS trial (NCT06173518).1
Findings presented at the
Obe-Cel in Pediatric Relapsed/Refractory B-ALL
Remission was ongoing in 20 patients. Six of these patients underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) following obe-cel per investigator decision. Of the 6 patients who underwent transplant, 5 lost CAR T-cell persistence, and 4 were in B-cell recovery. Among the 14 patients to not undergo transplant, 11 had ongoing B-cell aplasia.
Regarding safety, grade 3 or higher CRS and ICANS each occurred in 8.7% of evaluable patients (n = 23). Any-grade CRS and any-grade ICANS were reported in 52.2% and 17.4% of patients, respectively. The median time to onset of any-grade CRS was 7.0 days (range, 1-11), and the median time to onset of any-grade ICANS was 8.5 days (range, 8-20). Infections of any grade occurred in 65.2% of patients, and 21.7% of patients had grade 3 or higher infections. Sepsis was reported in 8.7% of patients. The any-grade and grade 3 or higher rates of febrile neutropenia were 30.4% and 26.1%, respectively, and no treatment-related mortality was reported.
“While longer follow-up is needed, results demonstrate promising safety and preliminary efficacy in pediatric patients with relapsed/refractory B-ALL treated with obe-cel,” lead study author Sara Ghorashian, MD, PhD, FRCPath, and colleagues wrote in a poster presentation of the data. “These preliminary findings support further exploration of obe-cel in pediatric relapsed/refractory B-ALL. Planning for the phase 2 expansion is underway.”
Ghorashian is a clinical associate professor and honorary consultant in the Department of Developmental Biology & Cancer at University College London in the United Kingdom.
In November 2024,
Ghorashian explained that pediatric patients with relapsed/refractory B-ALL have a poor prognosis, particularly those who relapse early.1 Although allo-HSCT is an established therapy for this patient population, study authors noted that efficacious therapies with greater tolerability are needed for pediatric patients with relapsed/refractory B-ALL.
After obe-cel displayed promising efficacy and safety in a pediatric patient population in the phase 1 CARPALL trial (NCT02443831),3 investigators launched the single-arm, open-label, international, multicenter CATULUS trial to evaluate the CAR T-cell therapy in patients under 18 years of age with CD19-positive relapsed/refractory B-ALL or B-cell non-Hodgkin lymphoma.1
Patients needed to have primary refractory disease, be in very high–risk first relapse, have relapsed/refractory disease after at least 2 lines of therapy, or be post–allo-HSCT. Notably, patients with Philadelphia chromosome (Ph)–positive disease were allowed to participate if they had received at least 1 prior TKI.
After leukapheresis, bridging therapy was allowed at investigator discretion. Patients underwent lymphodepleting chemotherapy with fludarabine at 30 mg/m2 on days –6, –5, –4, and –3 plus cyclophosphamide at 500 mg/m2 on days –6 and –5. Obe-cel was then infused on day 1 at a target dose of 1.0 x 106 CAR T cells/kg (± 25%).
The frequency and severity of adverse effects served as the trial’s primary end point. Secondary end points included ORR, CAR T-cell expansion, CAR T-cell persistence, and B-cell aplasia.
All patients infused with obe-cel (n = 23) had a median age of 9.2 years (range, 0.8-17.8); 43.5% were at least 12 years of age, 52.2% were female, and 73.9% were not Hispanic or Latino. Down syndrome was reported in 4.3% of patients at baseline, 8.7% of patients harbored KMT2A rearrangements, and 13.0% of patients had Ph-positive disease. Additionally, 26.1% of patients had primary refractory disease, 21.7% of patients were in first relapse, and 52.2% of patients were in second or greater relapse. Prior treatments included allo-HSCT (13.0%) and blinatumomab (Blincyto; 26.1%); no patients had received prior inotuzumab ozogamicin (Besponsa).
Additionally, the median bone marrow blast percentage at screening was 5.0% (range, 0%-95%), and 56.5% of patients had a level of at least 5% at screening. CR/CR with incomplete hematologic recovery (CRi) was reported in 21.7% of patients at screening, who all had MRD-positive disease. Among 78.3% of patients not in CR/CRi at screening, 60.9% had bone marrow and/or blood disease with or without extramedullary disease (EMD), and 17.4% had isolated EMD. Overall, 26.1% of patients had EMD at screening, which was detected in the central nervous system (21.7%), testis (8.7%), or other (4.3%).
In the 5 patients who experienced grade 3 or higher infections, none of these infections were deemed related to obe-cel; these infections included sepsis (n = 2), respiratory syncytial virus (n = 1), device-related infection (n = 1), device-related sepsis (n = 1), and splenic infection (n = 1).
Most instances of neutropenia resolved by month 2; however, unresolved grade 3 or higher cytopenias reported at month 2 included neutropenia (n = 4) and anemia (n = 1).
Pharmacokinetic data demonstrated that after infusion, the geometric mean maximal CAR T-cell expansion was 90,383 copies/µg (geometric coefficient of variation [Geo-CV%], 142.3%). The median time to maximal expansion was 14 days (range, 9-21). The overall exposure during the first 28 days was 803,308 copies/µg DNA x days (Geo-CV%, 172.0%).
