Abstract 838P
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
Outcome | Weighted axi-cel versus epcoritamab (95% confidence interval) | |
Base case (C12) ESS=30 | Scenario (C1246) ESS=43 | |
ORR OR | 1.55 (0.65−3.69) | N/A |
PFS HR | 0.51 (0.31−0.85) | N/A |
DOR HR | 0.84 (0.46−1.52) | N/A |
OS HR | 0.77 (0.45−1.30) | 0.67 (0.41−1.10) |
G3+ CRS OR | 5.31 (1.21−23.32) | 4.43 (1.10−17.92) |
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.
Resources from the same session
832P - Characterisation of EXS73565: A potent and selective MALT1 inhibitor with low drug-drug interaction risk and potential in lymphoma
Presenter: Major Gooyit
Session: Poster session 18
833P - New targets for adult T cell leukemia/lymphoma (ATLL): A map for ATLL immunotherapy
Presenter: Zahra Rezaei Borojerdi
Session: Poster session 18
834P - Phase II clinical study of VR-CAP regimen for first-line treatment of marginal zone lymphoma
Presenter: Junfeng Chu
Session: Poster session 18
835P - A safe and effective immunochemotherapy with oral sobuzoxane and etoposide for untreated diffuse large B cell lymphoma patients aged 80 and over
Presenter: Kaname Miyashita
Session: Poster session 18
840P - Genomic landscape, immune characteristics and prognostic mutation signature of extranodal NK/T cell lymphoma, nasal type in China
Presenter: Yue Chai
Session: Poster session 18
841P - Ki67-revised risk index to risk-stratify patients with extra-nodal natural killer/T cell lymphoma
Presenter: Shuo Li
Session: Poster session 18
842P - Multicenter real-world study of newly diagnosed advanced-stage extranodal natural killer/T cell lymphoma (ENKTL): Proposal for intensive therapy
Presenter: Yu-Ce Wei
Session: Poster session 18