839P - Matching-adjusted indirect comparison (MAIC) of axicabtagene ciloleucel (axi-cel) and glofitamab (glofit) in relapsed/refractory (R/R) large B cell lymphoma (LBCL) after at least two prior systemic therapies (3L+)

Background

Axi-cel is a chimeric antigen receptor T-cell (CAR T) therapy evaluated in ZUMA-1 while glofit is a bispecific antibody evaluated in NP30179. Without direct evidence, we estimated relative treatment effects of axi-cel versus glofit in 3L+ R/R LBCL using an unanchored MAIC.

Methods

A logistic propensity score model was used to weigh ZUMA-1 patient-level data to match the baseline characteristics of NP30179 (N=155) on pre-specified clinically relevant prognostic factors: ECOG performance status, disease stage, response to last therapy, prior lines of therapy, lactate dehydrogenase, 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 (G3+) cytokine release syndrome (CRS) and neurological events (NE). Relative effects were hazard/odds ratios (HR/OR). Base case analyses included ZUMA-1 pivotal Cohorts 1+2 (C12; N=101) while scenario analyses of OS, CRS, and NE included ZUMA-1 safety Cohorts 4+6 (C1246; N=182).

Results

Axi-cel improved ORR and PFS versus glofit (Table; effective sample size [ESS] = 32). Median PFS for axi-cel versus glofit were 15 and 11.4 months, respectively. DOR and OS were comparable with point estimates favoring axi-cel. In the scenario analysis, OS was also improved with axi-cel (ESS = 63). Axi-cel was associated with higher rates of G3+ CRS and NEs but the former was comparable in the scenario analysis.

Table: 839P

MAIC results

Conclusions

Findings suggests axi-cel may be more efficacious in terms of ORR and PFS compared to glofit but with a higher risk of certain adverse events. Of note, median follow-up was shorter in NP30179 (12.6 months) than ZUMA-1 (60 months [C12] and 24 months [C46]) and differences in prior CAR T use could not be accounted for (34% in NP30179 versus 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

F.L. Locke: Financial Interests, Institutional, Advisory Role, Honoraria from Gilead and Pfizer; scientific advisory role and consultant to AbbVie, ADC, Curio Science, Epizyme, Gilead, Janssen, Kite, a Gilead Company, Pfizer, Nektar, Novartis, Syncopation, and TGR therapeutics: 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. M.D. Ray, C. Fu, A.R. Patel: Financial Interests, Personal and Institutional, Full or part-time Employment, Is a stockholder and current employee of Kite, a Gilead Company: Kite Pharma. 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.