Obe-cel is associated with durable survival outcomes in relapsed/refractory B-ALL, regardless of BOR of CR or CRi.
Findings from a post hoc analysis of the phase 1b/2 FELIX trial (NCT04404660) demonstrated that obecabtagene autoleucel (obe-cel; Aucatzyl) yielded durable clinical benefit in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), regardless of best overall response (BOR) to the chimeric antigen receptor (CAR) T-cell therapy.1
Data presented at the
For patients in CR at month 3, the 24-month EFS and OS probabilities were 53.2% and 55.5%, respectively. These respective rates were 72.9% and 83.3% for patients in CRi.
“Most patients in CRi by month 1 will increase their blood counts and achieve a CR by 3 months,” presenting study author Manuel Guerreiro, MD, PhD, of Hospital Universitari in Valencia, Spain, said during the presentation. “A substantial number of patients who responded to obe-cel…had sustained survival benefit, regardless of BOR.”
In November 2024,
The open-label, multicenter trial enrolled patients at least 18 years of age with relapsed/refractory B-ALL who had CD19-positive disease within 1 month of screening.3 Patients with Philadelphia chromosome (Ph)–positive disease were allowed to enroll if they were intolerant to a tyrosine kinase inhibitor (TKI), had progressed following 2 prior lines with a TKI, had progressed on 1 line of a second-generation TKI, or were contraindicated for a TKI. An ECOG performance status of 0 or 1 was required for all patients.
Following leukapheresis and bridging therapy, patients underwent lymphodepleting chemotherapy with fludarabine at 30 mg/m2 per day for 4 days and cyclophosphamide at 500 mg/m2 per day for 2 days.1
Obe-cel administration was guided by tumor burden, with the CAR T-cell therapy given as a split dose on days 1 and 10 for a total target dose of 410 x 106 CAR-positive T cells.1,3
CR/CRi rate per independent review committee assessment served as the trial’s primary end point; secondary end points included duration of response, EFS, OS, safety, CAR T-cell expansion, and CAR T-cell persistence.3
To achieve a CR, patients needed to have a bone marrow blast level of less than 5%; have no extramedullary disease; have no circulating lymphoblasts in the peripheral blood; have an absolute neutrophil count (ANC) of more than 1000/µL; and have a platelet count of more than 100,000/µL.1 No platelet transfusions in the last 7 days, no short-acting granulocyte colony-stimulating factor (G-CSF) in the last 3 days, and no long-acting G-CSF in the last 14 days were also required for CR.
CRi criteria mirrored CR criteria, except for platelet count (≤ 100,000/µL) and ANC (< 1000/µL).
In patients who achieved a CR/CRi (n = 99), the median age at baseline was 50.0 years (range, 20-81); 54% of patients were male, and 67.7% were not Hispanic or Latino. Patients had received a median of 2.0 prior lines of therapy (range, 1-5), and 33.3% had received at least 3 prior lines. Additionally, 8.1% of patients had disease refractory to all prior lines of therapy, 26.3% had disease refractory to first-line therapy, and 46.5% had disease refractory to their last line of therapy.
Prior treatments included blinatumomab (Blincyto; 38.4%), inotuzumab ozogamicin (Besponsa; 26.3%), blinatumomab plus inotuzumab ozogamicin (15.2%), blinatumomab or inotuzumab ozogamicin (49.5%), and allogeneic hematopoietic stem cell transplantation (allo-HSCT; 47.5%).
Furthermore, 33.3% of patients had Ph-positive disease at lymphodepletion. Patients had a median bone marrow blast percentage of 38.0% (range, 0%-100%), with 30.3% of patients harboring a blast percentage above 75%. The median bone marrow blast percentage at lymphodepletion was 30.0% (range, 0%-100%). Additionally, 19.2% of patients had extramedullary disease at screening; this rate decreased to 16.2% after lymphodepletion.
The landmark analysis included patients who achieved a CR/CRi (n = 99) among the population of all infused patients (n = 127). Among the 99 patients to experience a CR/CRi by month 3, 24 were subsequently excluded from the landmark analysis due to morphological relapses (n = 7), receipt of allo-HSCT (n = 11), unconfirmed CR/CRi (n = 2), and death due to reasons other than the underlying cancer (n = 4).
Among the 75 patients ultimately included in the landmark analysis, 32 converted from CRi at month 1 to CR by month 3, representing 63% of all patients who achieved CR by month 3.
Findings also showed that in evaluable patients (n = 99), the median time to a platelet count recovery of at least 50 x 109/L was 0.7 months (95% CI, 0.30-1.68). Notably, 4 patients in CRi had persistent thrombocytopenia by month 6. No bleeding events were reported among these patients, and only 1 patient in this group had persistent thrombocytopenia through month 12, which resolved.
Furthermore, the median time to neutrophil recovery to at least 0.5 x 109/L was 0.7 months (95% CI, 0.49-0.92). Two patients had persistent neutropenia at month 3, but no instances of neutropenia were reported beyond 4.5 months. Notably, patients who underwent allo-HSCT (n = 47) experienced similar neutrophil recovery outcomes compared with those who did not undergo transplant (n = 52), with median times to recovery of 0.7 months (95% CI, 0.49-0.92) and 0.7 months (95% CI, 0.49-1.81), respectively.
Data also showed that infection led to death in 3 patients who achieved remission but did not proceed to allo-HSCT or experience relapse. These infections included sepsis (n = 2) and pneumonia (n = 1). One instance of sepsis leading to death occurred within 3 months of treatment; the other instance and the pneumonia event were reported during long-term follow-up.
Disclosures: Guerreiro reported serving in a consulting role for Bristol Myers Squibb, Gilead Sciences, Medac, Merck Sharp & Dohme, Novartis, Pierre Fabre, and Takeda.
