Matching-Adjusted Indirect Comparison of Obecabtagene Autoleucel vs. Blinatumomab Inotuzumab Ozogamicin and Ponatinib in Relapsed or Refractory Adult B-cell Acute Lymphoblastic Leukemia
Author(s)
Noemi A. Hardi, BSc, MSc1, Caroline Barwood, MSc1, Stephanie Fisher, BSc, MSc1, Jessica Dempsey, BSc1, dilip Patel, BSc2, David Bertwistle, BSc, MSc, PhD2, Martin Brown, MSc, MA2.
1FIECON, a Herspiegel Company, London, United Kingdom, 2Autolus Therapeutics, London, United Kingdom.
1FIECON, a Herspiegel Company, London, United Kingdom, 2Autolus Therapeutics, London, United Kingdom.
OBJECTIVES: Obecabtagene autoleucel (obe-cel) is an autologous chimeric antigen receptor (CAR) T-cell therapy which was granted conditional regulatory approval for the treatment of relapsed or refractory (R/R) adult B-cell acute lymphoblastic leukaemia (ALL) in the UK by the Medicines and Healthcare products Regulatory Agency in April, 2025. Immunotherapies blinatumomab and inotuzumab ozogamicin (inotuzumab) and tyrosine kinase inhibitor (TKI) ponatinib, are widely used for treatment of R/R adult B- ALL. To assess the comparative efficacy of obe-cel versus blinatumomab, inotuzumab and ponatinib, unanchored matching-adjusted indirect comparisons (MAICs) were conducted using patient-level data from the single-arm phase Ib/II FELIX trial [obe-cel] and aggregate data from comparator trials (TOWER [blinatumomab], INO-VATE [inotuzumab], and PACE [ponatinib]).
METHODS: FELIX patients were matched to each comparator trial baseline characteristics on primary refractory disease status, percentage bone marrow blasts at screening, prior lines of therapy, duration of first remission ≤12 months, Eastern Cooperative Oncology Group (ECOG) status, Philadelphia chromosome (Ph) presence, age, race, prior stem cell transplant (SCT), and sex, where available. Weighted Cox proportional hazards models were used for the primary outcomes, event-free survival (EFS) and overall survival (OS), with additional clinically relevant endpoints evaluated. Scenario analyses were also conducted.
RESULTS: In the infused primary cohort of FELIX, adjusted results significantly favoured obe-cel when compared to blinatumomab in the Ph- population (EFS: HR=0.32 [0.21,0.48]; OS: HR=0.48 [0.33,0.71]), and ponatinib in the Ph+ population (EFS: HR=0.26 [0.13,0.49]; OS: HR=0.16 [0.04,0.54]). In the overall (any Ph status) population, the MAIC demonstrated a numerical benefit in both EFS and OS for obe-cel versus inotuzumab (EFS: HR=0.90 [0.60,1.35]; OS: HR=0.80 [0.59,1.10]). Outcomes from unadjusted analyses were directionally consistent with weighted outcomes and showed statistical significance across all comparisons.
CONCLUSIONS: MAIC findings suggest that obe-cel offers clinically meaningful improvements in outcomes compared to inotuzumab, blinatumomab, and ponatinib in patients with R/R B-cell ALL.
METHODS: FELIX patients were matched to each comparator trial baseline characteristics on primary refractory disease status, percentage bone marrow blasts at screening, prior lines of therapy, duration of first remission ≤12 months, Eastern Cooperative Oncology Group (ECOG) status, Philadelphia chromosome (Ph) presence, age, race, prior stem cell transplant (SCT), and sex, where available. Weighted Cox proportional hazards models were used for the primary outcomes, event-free survival (EFS) and overall survival (OS), with additional clinically relevant endpoints evaluated. Scenario analyses were also conducted.
RESULTS: In the infused primary cohort of FELIX, adjusted results significantly favoured obe-cel when compared to blinatumomab in the Ph- population (EFS: HR=0.32 [0.21,0.48]; OS: HR=0.48 [0.33,0.71]), and ponatinib in the Ph+ population (EFS: HR=0.26 [0.13,0.49]; OS: HR=0.16 [0.04,0.54]). In the overall (any Ph status) population, the MAIC demonstrated a numerical benefit in both EFS and OS for obe-cel versus inotuzumab (EFS: HR=0.90 [0.60,1.35]; OS: HR=0.80 [0.59,1.10]). Outcomes from unadjusted analyses were directionally consistent with weighted outcomes and showed statistical significance across all comparisons.
CONCLUSIONS: MAIC findings suggest that obe-cel offers clinically meaningful improvements in outcomes compared to inotuzumab, blinatumomab, and ponatinib in patients with R/R B-cell ALL.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO163
Topic
Clinical Outcomes, Study Approaches
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Genetic, Regenerative & Curative Therapies, Oncology, Personalized & Precision Medicine