838P - Matching-adjusted indirect comparison (MAIC) of axicabtagene ciloleucel (axi-cel) and epcoritamab (epcor) in relapsed/refractory (R/R) large B cell lymphoma (LBCL) after at least two prior systemic therapies (3L+)

Background

Axi-cel, a chimeric antigen receptor T-cell (CAR T) therapy evaluated in ZUMA-1, and epcor, a bispecific antibody evaluated in EPCORE NHL-1, are treatments for R/R LBCL. In the absence of a head-to-head trial, we conducted an unanchored MAIC to estimate relative treatment effects of axi-cel versus epcor in 3L+ R/R LBCL.

Methods

ZUMA-1 patient-level data were matched (using a logistic propensity score model) to baseline characteristics representing pre-specified clinically relevant prognostic factors in EPCORE NHL-1 (N=157): International Prognostic Index score, ECOG performance status, disease stage, response to last therapy, number of prior lines, primary refractoriness, LBCL subtype, and prior autologous stem cell transplant. Outcomes were objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and grade ≥3 cytokine release syndrome (G3+ CRS). Neurotoxicity was not analysed as definitions differed. Relative effects were hazard/odds ratios (HR/OR). Base case analyses included ZUMA-1 pivotal Cohorts 1+2 (C12; N=101). Scenario analyses of OS and CRS added ZUMA-1 safety Cohorts 4+6 (C1246; N=182).

Results

The effective sample size (ESS) for axi-cel was 30 in the base-case (Table). Axi-cel improved PFS (median 12.5 months) versus epcor (median 4.4 months). ORR, DOR and OS results were comparable with point estimates favoring axi-cel. A higher rate of G3+ CRS was associated with axi-cel but the difference was reduced in the scenario analysis.

Table: 838P

MAIC results

Conclusions

Our MAIC suggests axi-cel may be more efficacious in terms of PFS versus epcor but with a higher risk of CRS G3+. Of note, median follow-up was short in EPCORE NHL-1 (10.7 months) compared to ZUMA-1 (60 months [C12] and 24 months [C46]) and differences in prior CAR T exposure could not be adjusted for (39% in EPCORE NHL-1 vs 0% in ZUMA-1).

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Kite, a Gilead Company.

Funding

Kite, a Gilead Company.

Disclosure

O.O. Oluwole: Financial Interests, Institutional, Advisory Role, Scientific advisory role and consultant to Kite Pharma, Allogene, CERo Therapeutics, Novartis, BlueBird Bio, Bristol Myers Squibb, National Cancer Institute, Leukemia and Lymphoma Society: Kite Pharma. M.D. Ray, H. Smith, C.L. Bellasis Spooner, A.R. Patel: Financial Interests, Personal and Institutional, Full or part-time Employment, A stockholder and current employee of Kite, a Gilead company: Kite Pharma. J.M. Chen, K. Chan, I. Zhang, S. Keeping: Financial Interests, Institutional, Full or part-time Employment, PRECISIONheor received consulting fees from Kite, a Gilead Company: PRECISIONheor. F.L. Locke: Financial Interests, Institutional, Advisory Role, Honoraria from Gilead and Pfizer; scientific advisory role and consultant for AbbVie, ADC, Curio Science, Epizyme, Gilead, Janssen, Kite, a Gilead Company, Pfizer, Nektar, Novartis, Syncopation, and TGR therapeutics: Kite Pharma.