Abstract A013: Impact of putative cell of origin on CD19+CAR-T outcomes in patients with large B-cell lymphoma
Muhammad Bilal AbidAbstract
Background:
While the putative cell of origin (COO) (GCB vs non-GCB) impacts prognosis and treatment responses in LBCL as well as with autoHCT (Iqbal et al. CLML 2022), the impact of COO on CAR-T outcomes remains elusive. Additionally, while survival following axi-cel therapy (CAR-T in second line) was prolonged compared to SOC for both COO subtypes, the studies were not designed to detect differences in outcomes based on COO (Locke et al. NEJM 2022).
Methods:
We retrospectively examined the impact of COO in patients with LBCL receiving commercial CD19+CAR-T between 2019-2024, stratified by lines of therapy (LOT; 2L vs 3L+). Axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) were included in 2L and axi-cel, liso-cel and tisagenlecleucel (tisa-cel) in third line and beyond (3L+) setting. COO stratification was based on Hans algorithm and response to CAR-T per Lugano PET/CT criteria. Progression free survival (PFS) was the primary endpoint.
Results:
Of 344 patients, 59% (n=203) patients had GCB and 41% (n=141) had non-GCB subtype. Axi-cel accounted for 79.1% (n=272) CAR-T, liso-cel 17.2% (n=59), and tisa-cel 3.8% (n=13); and 75% (n=257) patients received CAR-T in 3L+ vs 25% (n=87) in 2L. Median interval between diagnosis and CAR-T was 16.6 months, 48% (n=165) had HCT-CI33, 59.9% (n=172) elevated LDH, 9.5% (n=25) bulky disease (>10cm), 15.7% (n=54) ECOG32, and 45.5% (n=154) IPI33. Of 132 patients who died, primary cause of death was disease progression in 69.5% patients, infections (11.5%), secondary malignancy (6.1%), ICANS (3.1%), and CRS (0.8%). Median PFS in GCB was 13.8 vs 6.7 months in non-GCB cohort. In multivariate analysis adjusted for LOT, HCT-CI, prior overall response rate (ORR), and ECOG, PFS was significantly superior in GCB vs non-GCB arm (HR, 1.40; p=0.028). Median OS in GCB arm was 24.1 vs 18.3 months in non-GCB. In multivariate analysis adjusted for LOT, prior ORR, and ECOG, OS was significantly superior in GCB arm vs non-GCB (HR, 1.46; p=0.032). While there was no significant difference in median PFS (p=0.49) and OS (p=0.82) between 2 COO arms with CAR-T in 2L, median PFS (13.5 vs 6.2 months; p=0.0176) and OS (28.6 vs 14 months; p=0.028) were significantly superior in GCB arm with CAR-T in 3L+ vs non-GCB. There were no significant differences in PFS or OS at 1, 2, and 3 years between the 2 COO subtypes in 2L, whereas these were superior in GCB arm, when CAR-T was given in 3L+. In multivariate analysis, CAR-T in 2L vs 3L+ was associated with superior PFS (HR, 1.65; p=0.013), however, there was no significant difference in OS (HR, 1.23; p=0.366).
Conclusion:
These results demonstrate that GCB subtype have a superior PFS (HR 1.4) and OS (HR 1.5) compared to non-GCB from CD19+CAR-T. Additionally, GCB subtype derive a significant survival benefit when CAR-T is given in 3L+ setting. Consistent with existing literature, CAR-T in earlier lines (2L vs 3L+) confers a PFS advantage (HR 1.65).
Citation Format:
Muhammad Bilal Abid. Impact of putative cell of origin on CD19+CAR-T outcomes in patients with large B-cell lymphoma [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A013.