Obe-cel Demonstrates Deep Responses in Patients With R/R B-ALL
Among 94 patients who were treated with obe-cel in the trial, 76% achieved a CR or CRi.
Autolus Therapeutics’ obecabatagene autoleucel (obe-cel), an investigational autologous CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, has produced deep responses among adult patients with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) treated in the pivotal phase 2 FELIX clinical trial (NCT04404660). The results were presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois, by Claire Roddie, MD, PhD, FRCPath, MBChB, MRCP, an associate professor at University College London.
Among 94 patients who were treated with obe-cel in the trial, 76% achieved either a complete remission (CR) (54.3%) or a CR with incomplete blood count recovery (CRi) (21.3%). The overall response rate was 76% (95% CI, 66-84; 1-sided P < .0001) and 97% of patients who responded and had evaluable samples achieved minimal residual disease (MRD) negativity at the 10-4 level when evaluated by flow cytometry. At a median follow-up of 9.5 months, 61% of patients who responded continued to remain in remission without receiving new anticancer therapies. The median duration of response was 14.1 months (95% CI, 5.9, not estimable). It was noted that 13% of the patients who responded and proceeded to stem cell transplantation (SCT) while in remission were censored at the time of SCT.
In terms of safety, 71 of the treated patients (75.5%) experienced cases of cytokine release syndrome (CRS), with 3 patients (3.2%) experiencing CRS cases that were grade 3 or higher. Meanwhile, 24 of the treated patients (25.5%) experienced cases of immune effector cell-associated neurotoxicity syndrome (ICANS), with 7 patients (7.4%) experiencing ICANS cases that were grade 3 or higher. Roddie drew attention to the fact that 6 of the 7 patients who experienced grade 3 or higher ICANS had greater than 75% bone marrow (BM) blasts at the time of preconditioning. She also noted that 56% of the treated patients received tocilizumab for CRS, 17% of the treated patients received steroids for CRS, and 3% of the treated patients received vasopressor support for CRS. The most common grade 3 or higher treatment-emergent adverse events experienced by patients in the trial were neutropenia, which occurred in 36.2% of patients; thrombocytopenia, which occurred in 25.5% of patients; febrile neutropenia, which occurred in 25.5% of patients; and anemia, which occurred in 19.1% of patients. Roddie also pointed out that 1 patient death deemed related to obe-cel occurred, which was attributed to hemophagocytic lymphohistiocytosis and neutropenic sepsis.
READ MORE: Tecartus Achieves High Response Rates Among Patients With R/R B-ALL in Real-World Data
The ages of the 94 patients treated with obe-cel in the study ranged from 20 years to 81 years (median, 50). Exactly half of these patients were female and 25 of the treated patients (26.6%) were Philadelphia chromosome-positive. The number of prior lines of therapy received by the patients treated with obe-cel ranged from 1 to 6 (median, 2), with 30.9% of the patients having received 3 or more prior lines of therapy. Roddie noted that 50 (53.2%) of the patients were refractory to their last line of prior therapy. Thirty-six (38.3%) of the treated patients had received prior allogeneic SCT, 33 (35.1%) had received prior treatment with blinatumomab, 30 (31.9%) had received prior treatment with inotuzumab, and 15 (16%) had received prior treatment with both blinatumomab and inotuzumab. The median percentage of BM blasts at screening was 49.5% (range, 6 to 100), the median percentage of BM blasts at preconditioning was 41.1% (range, 0 to 100), and 18 patients (19.1%) had extramedullary disease at preconditioning.
Roddie also discussed the manufacturing success for obe-cel in the trial, emphasizing that product was released for 94% of patients who underwent leukapheresis, that 84% of enrolled patients received the CAR-T product, and that the median vein to delivery time was 21 days. She additionally spoke about engraftment, highlighting that a Cmax of 114,982 copies/ug DNA (Geo-Mean; CV%, 287.6) and Tmax at 14 days (median, range 2 to 55) was observed.
“...We're dealing with a very difficult [to treat] patient population here,” Roddie concluded. “They're heavily pretreated, they're older, they're comorbid, they've got a lot of disease on board. There was a lot of extramedullary disease. But despite all of these odds being stacked against the product, obe-cel was able to achieve CR or CRi in 76% of those infused patients—and what's more, those responses were deep, MRD-negative responses.”
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REFERENCE
1. Roddie C, Sandhu KS, Tholouli E, et al. Safety and efficacy of obecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR, in relapsed/refractory adult B-cell acute lymphoblastic leukemia (r/r B-ALL): Top line results of the pivotal FELIX study. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #7000
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