Propensity score (PS) comparison between lisocabtagene maraleucel (liso-cel) plus ibrutinib combination therapy (combo) and liso-cel monotherapy (mono) cohorts from TRANSCEND CLL.

7037 Background: TRANSCEND CLL 004 (NCT03331198) is a phase 1/2, open-label, nonrandomized, multicohort study in adult patients (pt) with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma with liso-cel mono and liso-cel + ibrutinib combo cohorts. Given the study design, we performed PS matching/weighting to adjust for differences in key covariates between cohorts to compare efficacy and safety. Methods: Here, PS is the probability of receiving combo given the covariates and estimated by logistic regression. Covariates were hemoglobin, LDH, number of prior therapies, platelets, prior BTKi + venetoclax exposure, R/R on prior BTKi, and bulky disease for efficacy; and ALC, bulky disease, CRP, ferritin, and number of prior therapies for safety. PS balancing methods were optimal 1:1 matching, average treatment effect for treated pts (ATT) full matching, and ATT inverse probability of treatment weighting (IPTW). Efficacy endpoints were response (CR rate, ORR) and time to event endpoints (DOR, PFS, OS). Safety endpoints were proportions of pts with any-grade (gr)/gr ≥ 3 cytokine release syndrome (CRS) and investigator-identified neurological events (NE). Results: Fifty-one and 88 efficacy-evaluable pts were treated at dose level 2 (100 × 10 6 CAR + T cells) in the combo and mono cohorts, respectively. Before matching/weighting on PS, odds of achieving CR and overall response were statistically significantly higher for combo (Table). DOR did not differ between cohorts. For PFS and OS, HRs were lower with combo vs mono (not statistically significant [NS]). Odds of gr ≥ 3 CRS/NE were lower with combo vs mono (NS). After matching/weighting, odds of CR (except IPTW ATT) and overall response remained statistically significantly higher in combo. HRs for PFS and OS and ORs for gr ≥ 3 CRS/NE were numerically lower with combo vs mono (NS, except IPTW ATT for PFS). HRs for DOR were less but close to HR of 1. Conclusions: The liso-cel + ibrutinib combo demonstrated a trend for better efficacy and safety vs liso-cel mono, with statistically significant differences for CR rate and ORR. Clinical trial information: NCT03331198 . Efficacy and safety outcomes: combo vs mono. No adjustment ATT optimal 1:1 IPTW - ATT CR rate, OR (95% CI) 2.07* (1.01–4.28) 2.40* (1.05–5.66) 2.00(0.89–4.61) ORR, OR (95% CI) 3.96* (1.68–10.51) 3.43* (1.33–9.71) 4.18* (1.63–11.78) DOR, HR (95% CI) 0.98(0.51–1.87) 0.88(0.43–1.78) 0.96(0.50–1.85) PFS, HR (95% CI) 0.62(0.37–1.02) 0.61(0.35–1.05) 0.59* (0.35–0.98) OS, HR (95% CI) 0.70(0.38–1.28) 0.73(0.37–1.43) 0.66(0.36–1.22) CRS, OR (95% CI) 0.63(0.26–1.56) 0.67(0.24–1.84) 0.69(0.24–1.88) Gr ≥ 3 CRS, OR (95% CI) 0.23(0.01–1.35) 0.49(0.02–5.28) 0.26(0.01–1.94) NE, OR (95% CI) 0.84(0.41–1.68) 0.92(0.40–2.08) 1.10(0.48–2.52) Gr ≥ 3 NE, OR (95% CI) 0.56(0.19–1.45) 0.58(0.16–1.89) 0.68(0.19–2.30) *Statistically significant difference at 5% level.