Comparing CAR T-Cell Therapies for LBCL: Insights From CART-SIE Study

Author(s):

Key Takeaways

Axi-cel demonstrated superior progression-free survival compared to tisa-cel, despite a higher toxicity profile, including increased neurotoxicity and cytokine release syndrome.
The CAR-HEMATOTOX score effectively predicted hematologic toxicity and 1-year overall survival outcomes, highlighting its utility in clinical decision-making.
Axi-cel showed better efficacy in patients not responding to bridging therapy, with improved progression-free and overall survival rates compared to tisa-cel.
Secondary malignancies were observed in 4.1% of patients, but a causal relationship with CAR T-cell therapy was not established due to limited follow-up.

Real-world study compares the efficacy and safety of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), finding that axi-cel provides superior progression-free survival but with higher toxicity.

A recent multicenter study published in Blood Cancer Discovery examined the comparative efficacy and toxicity of 2 leading CAR T-cell therapies, axicabtageneciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), in 485 patients with relapsed or refractory large B-cell lymphoma (LBCL).¹ The research, part of the CART-SIE database initiative by the Italian Society of Hematology, conducted across 21 Italian centers, used inverse propensity score weighting to match baseline characteristics between the 2 treatment groups.

CAR T cells attacking cancer cells, illustrated | image credit: Anastasiia - stock.adobe.com

According to the study, axi-cel demonstrated superior efficacy in progression-free survival (PFS) at 1 year, with a rate of 46.5% compared to 34.1% for tisa-cel (P = .0009). The overall survival (OS) rates at 1 year were not significantly different between the therapies, with a 1-year OS of 70.8% for axi-cel vs 60.4% for tisa-cel (95% CI, 64.1%–87.2%; P = .1709).

Key findings from the study reveal significant differences in toxicity profiles and efficacy outcomes between axi-cel and tisa-cel. All-grade cytokine release syndrome (CRS) rates for axi-cel reached 89.3%, compared to 78.6% for tisa-cel (OR, 0.44; 95% CI, 0.26–0.74; P = .0017). However, grade ≥3 CRS was observed at similar rates in both groups, affecting 8.6% of axi-cel patients and 7.1% of tisa-cel patients. Neurotoxicity was also higher in axi-cel-treated patients at 32.2%, in contrast to 9.9% for tisa-cel (OR, 0.23; 95% CI, 0.14–0.38; P < .0001).

Despite these toxicity differences, the 1-year non-relapse mortality (NRM) remained low at 2.0% (95% CI, 1.0%–3.9%), with infection-related causes accounting for most NRM cases, occurring similarly across both groups. Additionally, the study found that the CAR-HEMATOTOX score, a predictive model for assessing hematologic toxicity risk based on markers of hematopoietic reserve and baseline inflammation, was not only able to forecast hematologic toxicity but also 1-year OS outcomes, with a survival rate of 77.2% for patients with low CAR-HEMATOTOX scores versus 51.5% for those with high scores (P < .0001). Similarly, the 1-year PFS for patients with a low CAR-HEMATOTOX score was 43.6%, versus 29% for those with a high score (P = .0003).

Among patients who did not respond to bridging therapy, axi-cel demonstrated superior PFS and OS compared to tisa-cel, with a 1-year PFS rate of 37.5% for axi-cel versus 22.7% for tisa-cel (P = .0059), and a 1-year OS of 61.8% with axi-cel versus a 48.4% with tisa-cel (P = .1844). Additionally, the study noted those patients who received a bridging therapy regimen including polatuzumab-vedotin (pola; Polivy) had better PFS outcomes than those receiving other types of bridging therapy, with a 1-year PFS rate of 47.6%, compared to 35.5% for those on nonpola-based regimens (P = .0340).

Another important finding of the study was the development of secondary primary malignancies. Over a median follow-up of 13 months (IQR: 6.32–23.55), 20 patients (4.1%) developed secondary malignancies, including hematologic cancers such as myelodysplastic syndromes and solid tumors. The authors note that “establishing a causal relationship between CAR T-cell therapy and the development of secondary malignancies was not feasible” due to the relatively short follow-up period and small number of secondary malignancies identified.

This multicenter study provides a comprehensive comparison of axi-cel and tisa-cel in a real-world setting, reinforcing previous findings of axi-cel’s higher toxicity profilewhile also demonstrating superior efficacy.^2,3“These findings enable more informed selection of anti-CD19 CAR T-cell therapy, balancing bridging, safety, and efficacy considerations for individual patients,” the authors conclude, adding that “axi-cel is superior to tisa-cel in terms of PFS and should be preferred when patients failing bridging.”

References:

Stella F, Chiappella A, Casadei B, et al. A multicenter real-life prospective study of axicabtageneciloleucel versus tisagenlecleucel toxicity and outcomes in large B-cell lymphomas. Blood Cancer Discov. 2024;5(5):318-330. doi:10.1158/2643-3230.BCD-24-0052
Kuhnl A, Roddie C, Kirkwood AA, et al. A national service for delivering CD19 CAR-T in large B-cell lymphoma: the UK real-world experience. Br J Haematol. 2022;198(3):492-502. doi:10.1111/bjh.18209
Kwon M, Iacoboni G, Reguera JL, et al. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma. Haematologica. 2023;108(1):110-121. doi:10.3324/haematol.2022.280805