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Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S260

Type: Oral Presentation

Session title: Gene therapy and cellular immunotherapy - Clinical 2

Background

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). In a previous propensity score matching (PSM) analysis (Bachy et al., ASH 2021) allowing for balanced comparison between axi-cel and tisa-cel outcomes, we reported on a prolonged progression-free survival (PFS) but a higher toxicity associated with axi-cel compared with tisa-cel. No OS difference was observed but the follow-up was short (6 months).

Aims

We aim at reporting on PSM analysis with longer follow-up and with additionnal patients treated with axi-cel or tisa-cel.

Methods
All patients treated in France with axi-cel or tisa-cel from the 1st July 2018 to the 1st October 2021 and included in the DESCAR-T registry were considered.

Propensity score matching (PSM) was used to create a balanced covariate distribution between a cohort of patients treated with tisa-cel and a cohort of patients treated with axi-cel. An exhaustive list of covariates was used for PSM : age, sex, LDH level, C reactive protein (CRP), time between last treatment and infusion, Eastern Cooperative Oncology Group (ECOG) performance status (PS), Ann Arbor stage, number of prior lines of treatment before CAR-T, bridging and response to bridging, prior stem cell transplant (SCT) either autologous or allogeneic, bulk assessed at lymphodepletion, centre, histological diagnosis. PSM was performed considering a 1:1 matching without replacement and with optimal matching applying a calliper width of the propensity score set at 0.1. Inverse probability of treatment weighting (IPTW) was used as another approach to further validate PSM analysis.

Results

809 patients from 25 French centres with R/R DLBCL after at least 2 lines of previous therapy had a commercial CAR-T order with axi-cel or tisa-cel and were registered in DESCAR-T. Out of 809 patients with a CAR-T order, 60 were not infused due to progression or death between leukapheresis and lymphodepletion and 20 did not proceed to lymphodepletion for other reasons. Finally, 729 proceeded to lymphodepletion and CAR-T infusion. In the 1:1 matched population (N=418, 209 patients treated with tisa-cel and 209 patients treated with axi-cel), the best ORR/CRR was 66/42% versus 80/60% for patients treated with tisa-cel compared with axi-cel, respectively (P<0.001 for both ORR and CRR comparisons). After a median FU of 11.7 months (95% CI, 10.5-12.0 months) the 1-yr PFS was 33% for tisa-cel and 47% for axi-cel (HR=1.65, 95% CI 1.26-2.18, P=0.0003). OS was also significantly longer following axi-cel infusion than following tisa-cel infusion (1-yr OS 63% versus 49%; HR=1.58, 95% CI, 1.13-2.21; P=0.0072). Similar findings were found using IPTW statistical approach. Grade 1-2 CRS were significantly more frequent with axi-cel than tisa-cel (P=0.004) but no significant difference was observed for grade 3 or more CRS (9% versus 5% for tisa-cel and axi-cel respectively, P=0.130). Regarding ICANS, both all grades and severe (i.e. grade ≥3) ICANS were significantly more frequent with axi-cel than tisa-cel. 48% of patients experienced ICANS after axi-cel infusion compared to 22% after tisa-cel infusion. 29 patients (14%) presented a grade ≥3 ICANS with axi-cel compared with 6 (3%) only with tisa-cel.

Conclusion

In conclusion, our matched-comparison study supports a higher efficacy but also a higher toxicity of axi-cel compared with tisa-cel in third or more treatment line for R/R DLBCL.

Keyword(s): CAR-T, Diffuse large B cell lymphoma, Lymphoma

Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S260

Type: Oral Presentation

Session title: Gene therapy and cellular immunotherapy - Clinical 2

Background

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). In a previous propensity score matching (PSM) analysis (Bachy et al., ASH 2021) allowing for balanced comparison between axi-cel and tisa-cel outcomes, we reported on a prolonged progression-free survival (PFS) but a higher toxicity associated with axi-cel compared with tisa-cel. No OS difference was observed but the follow-up was short (6 months).

Aims

We aim at reporting on PSM analysis with longer follow-up and with additionnal patients treated with axi-cel or tisa-cel.

Methods
All patients treated in France with axi-cel or tisa-cel from the 1st July 2018 to the 1st October 2021 and included in the DESCAR-T registry were considered.

Propensity score matching (PSM) was used to create a balanced covariate distribution between a cohort of patients treated with tisa-cel and a cohort of patients treated with axi-cel. An exhaustive list of covariates was used for PSM : age, sex, LDH level, C reactive protein (CRP), time between last treatment and infusion, Eastern Cooperative Oncology Group (ECOG) performance status (PS), Ann Arbor stage, number of prior lines of treatment before CAR-T, bridging and response to bridging, prior stem cell transplant (SCT) either autologous or allogeneic, bulk assessed at lymphodepletion, centre, histological diagnosis. PSM was performed considering a 1:1 matching without replacement and with optimal matching applying a calliper width of the propensity score set at 0.1. Inverse probability of treatment weighting (IPTW) was used as another approach to further validate PSM analysis.

Results

809 patients from 25 French centres with R/R DLBCL after at least 2 lines of previous therapy had a commercial CAR-T order with axi-cel or tisa-cel and were registered in DESCAR-T. Out of 809 patients with a CAR-T order, 60 were not infused due to progression or death between leukapheresis and lymphodepletion and 20 did not proceed to lymphodepletion for other reasons. Finally, 729 proceeded to lymphodepletion and CAR-T infusion. In the 1:1 matched population (N=418, 209 patients treated with tisa-cel and 209 patients treated with axi-cel), the best ORR/CRR was 66/42% versus 80/60% for patients treated with tisa-cel compared with axi-cel, respectively (P<0.001 for both ORR and CRR comparisons). After a median FU of 11.7 months (95% CI, 10.5-12.0 months) the 1-yr PFS was 33% for tisa-cel and 47% for axi-cel (HR=1.65, 95% CI 1.26-2.18, P=0.0003). OS was also significantly longer following axi-cel infusion than following tisa-cel infusion (1-yr OS 63% versus 49%; HR=1.58, 95% CI, 1.13-2.21; P=0.0072). Similar findings were found using IPTW statistical approach. Grade 1-2 CRS were significantly more frequent with axi-cel than tisa-cel (P=0.004) but no significant difference was observed for grade 3 or more CRS (9% versus 5% for tisa-cel and axi-cel respectively, P=0.130). Regarding ICANS, both all grades and severe (i.e. grade ≥3) ICANS were significantly more frequent with axi-cel than tisa-cel. 48% of patients experienced ICANS after axi-cel infusion compared to 22% after tisa-cel infusion. 29 patients (14%) presented a grade ≥3 ICANS with axi-cel compared with 6 (3%) only with tisa-cel.

Conclusion

In conclusion, our matched-comparison study supports a higher efficacy but also a higher toxicity of axi-cel compared with tisa-cel in third or more treatment line for R/R DLBCL.

Keyword(s): CAR-T, Diffuse large B cell lymphoma, Lymphoma

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