EHA Library - The official digital education library of European Hematology Association (EHA)

A MATCHED COMPARISON OF TISAGENLECLEUCEL AND AXICABTAGENE CILOLEUCEL CAR T CELLS IN RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: A REAL-LIFE LYSA STUDY FROM THE FRENCH DESCAR-T REGISTRY
Author(s): ,
Emmanuel Bachy
Affiliations:
Hematology,Hospices Civils de Lyon,Pierre Bénite,France;Hematology,Hospices Civils de Lyon,Pierre Bénite,Frankreich;Hematology,Hospices Civils de Lyon,Pierre Bénite,Francia;Hematology,Hospices Civils de Lyon,Pierre Bénite,France;Hematology,Hospices Civils de Lyon,Pierre Bénite,Francia;Hematology,Hospices Civils de Lyon,Pierre Bénite,Frankrijk;Hematology,Hospices Civils de Lyon,Pierre Bénite,França
,
Steven Le Gouill
Affiliations:
Institut Curie,Paris,France;Institut Curie,Paris,Frankreich;Institut Curie,Paris,Francia;Institut Curie,Paris,France;Institut Curie,Paris,Francia;Institut Curie,Paris,Frankrijk;Institut Curie,Paris,França;Institut Curie,Paris,Франция ;Institut Curie,Paris,Frankrike
,
Pierre Sesques
Affiliations:
Hospices Civils de Lyon,Pierre Bénite,France;Hospices Civils de Lyon,Pierre Bénite,Frankreich;Hospices Civils de Lyon,Pierre Bénite,Francia;Hospices Civils de Lyon,Pierre Bénite,France;Hospices Civils de Lyon,Pierre Bénite,Francia;Hospices Civils de Lyon,Pierre Bénite,Frankrijk;Hospices Civils de Lyon,Pierre Bénite,França;Hospices Civils de Lyon,Pierre Bénite,Франция ;Hospices Civils de Lyon,Pierr
,
Roberta Di Blasi
Affiliations:
AP-HP,Paris,France;AP-HP,Paris,Frankreich;AP-HP,Paris,Francia;AP-HP,Paris,France;AP-HP,Paris,Francia;AP-HP,Paris,Frankrijk;AP-HP,Paris,França;AP-HP,Paris,Франция ;AP-HP,Paris,Frankrike
,
Manson Guillaume
Affiliations:
CHU Rennes,Rennes,France;CHU Rennes,Rennes,Frankreich;CHU Rennes,Rennes,Francia;CHU Rennes,Rennes,France;CHU Rennes,Rennes,Francia;CHU Rennes,Rennes,Frankrijk;CHU Rennes,Rennes,França;CHU Rennes,Rennes,Франция ;CHU Rennes,Rennes,Frankrike
,
Guillaume Cartron
Affiliations:
CHU Montpellier,Montpellier,France;CHU Montpellier,Montpellier,Frankreich;CHU Montpellier,Montpellier,Francia;CHU Montpellier,Montpellier,France;CHU Montpellier,Montpellier,Francia;CHU Montpellier,Montpellier,Frankrijk;CHU Montpellier,Montpellier,França;CHU Montpellier,Montpellier,Франция ;CHU Montpellier,Montpellier,Frankrike
,
David Beauvais
Affiliations:
CHU Lille,Lille,France;CHU Lille,Lille,Frankreich;CHU Lille,Lille,Francia;CHU Lille,Lille,France;CHU Lille,Lille,Francia;CHU Lille,Lille,Frankrijk;CHU Lille,Lille,França;CHU Lille,Lille,Франция ;CHU Lille,Lille,Frankrike
,
Louise Roulin
Affiliations:
CHU Mondor,Paris,France;CHU Mondor,Paris,Frankreich;CHU Mondor,Paris,Francia;CHU Mondor,Paris,France;CHU Mondor,Paris,Francia;CHU Mondor,Paris,Frankrijk;CHU Mondor,Paris,França;CHU Mondor,Paris,Франция ;CHU Mondor,Paris,Frankrike
,
François Xavier Gros
Affiliations:
CHU Bordeaux,Bordeaux,France;CHU Bordeaux,Bordeaux,Frankreich;CHU Bordeaux,Bordeaux,Francia;CHU Bordeaux,Bordeaux,France;CHU Bordeaux,Bordeaux,Francia;CHU Bordeaux,Bordeaux,Frankrijk;CHU Bordeaux,Bordeaux,França;CHU Bordeaux,Bordeaux,Франция ;CHU Bordeaux,Bordeaux,Frankrike
,
Marie Thérèse Rubio
Affiliations:
CHU Nancy,Nancy,France;CHU Nancy,Nancy,Frankreich;CHU Nancy,Nancy,Francia;CHU Nancy,Nancy,France;CHU Nancy,Nancy,Francia;CHU Nancy,Nancy,Frankrijk;CHU Nancy,Nancy,França;CHU Nancy,Nancy,Франция ;CHU Nancy,Nancy,Frankrike
,
Pierre Bories
Affiliations:
CHU Toulouse,Toulouse,France;CHU Toulouse,Toulouse,Frankreich;CHU Toulouse,Toulouse,Francia;CHU Toulouse,Toulouse,France;CHU Toulouse,Toulouse,Francia;CHU Toulouse,Toulouse,Frankrijk;CHU Toulouse,Toulouse,França;CHU Toulouse,Toulouse,Франция ;CHU Toulouse,Toulouse,Frankrike
,
Jacques Olivier Bay
Affiliations:
CHU Clermont Ferrand,Clermont Ferrand,France;CHU Clermont Ferrand,Clermont Ferrand,Frankreich;CHU Clermont Ferrand,Clermont Ferrand,Francia;CHU Clermont Ferrand,Clermont Ferrand,France;CHU Clermont Ferrand,Clermont Ferrand,Francia;CHU Clermont Ferrand,Clermont Ferrand,Frankrijk;CHU Clermont Ferrand,Clermont Ferrand,França;CHU Clermont Ferrand,Clermont Ferrand,Франция ;CHU Clermont Ferrand,Clermont
,
Cristina Castilla Llorente
Affiliations:
GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS,Villejuif,France;GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS,Villejuif,Frankreich;GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS,Villejuif,Francia;GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS,Villejuif,France;GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS,Villejuif,Francia;GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS,Villejuif,Frankrijk;GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS,Vi
,
Sylvain Choquet
Affiliations:
CHU Pitié Salprétrière,Paris,France;CHU Pitié Salprétrière,Paris,Frankreich;CHU Pitié Salprétrière,Paris,Francia;CHU Pitié Salprétrière,Paris,France;CHU Pitié Salprétrière,Paris,Francia;CHU Pitié Salprétrière,Paris,Frankrijk;CHU Pitié Salprétrière,Paris,França;CHU Pitié Salprétrière,Paris,Франция ;CHU Pitié Salprétrière,Paris,Frankrike
,
Rene-Olivier Casasnovas
Affiliations:
CHU Dijon,Dijon,France;CHU Dijon,Dijon,Frankreich;CHU Dijon,Dijon,Francia;CHU Dijon,Dijon,France;CHU Dijon,Dijon,Francia;CHU Dijon,Dijon,Frankrijk;CHU Dijon,Dijon,França;CHU Dijon,Dijon,Франция ;CHU Dijon,Dijon,Frankrike
,
Mohamad Mothy
Affiliations:
CHU Saint Antoine,Paris,France;CHU Saint Antoine,Paris,Frankreich;CHU Saint Antoine,Paris,Francia;CHU Saint Antoine,Paris,France;CHU Saint Antoine,Paris,Francia;CHU Saint Antoine,Paris,Frankrijk;CHU Saint Antoine,Paris,França;CHU Saint Antoine,Paris,Франция ;CHU Saint Antoine,Paris,Frankrike
,
Stephanie Guidez
Affiliations:
CHU Poitiers,Poitiers,France;CHU Poitiers,Poitiers,Frankreich;CHU Poitiers,Poitiers,Francia;CHU Poitiers,Poitiers,France;CHU Poitiers,Poitiers,Francia;CHU Poitiers,Poitiers,Frankrijk;CHU Poitiers,Poitiers,França;CHU Poitiers,Poitiers,Франция ;CHU Poitiers,Poitiers,Frankrike
,
Magalie Joris
Affiliations:
CHU Amiens,Amiens,France;CHU Amiens,Amiens,Frankreich;CHU Amiens,Amiens,Francia;CHU Amiens,Amiens,France;CHU Amiens,Amiens,Francia;CHU Amiens,Amiens,Frankrijk;CHU Amiens,Amiens,França;CHU Amiens,Amiens,Франция ;CHU Amiens,Amiens,Frankrike
,
Mickael Loschi
Affiliations:
CHU Nice,Nice,France;CHU Nice,Nice,Frankreich;CHU Nice,Nice,Francia;CHU Nice,Nice,France;CHU Nice,Nice,Francia;CHU Nice,Nice,Frankrijk;CHU Nice,Nice,França;CHU Nice,Nice,Франция ;CHU Nice,Nice,Frankrike
,
Sylvain Carras
Affiliations:
CHU Grenoble,Grenoble,France;CHU Grenoble,Grenoble,Frankreich;CHU Grenoble,Grenoble,Francia;CHU Grenoble,Grenoble,France;CHU Grenoble,Grenoble,Francia;CHU Grenoble,Grenoble,Frankrijk;CHU Grenoble,Grenoble,França;CHU Grenoble,Grenoble,Франция ;CHU Grenoble,Grenoble,Frankrike
,
Julie Abraham
Affiliations:
CHU Limoges,Limoges,France;CHU Limoges,Limoges,Frankreich;CHU Limoges,Limoges,Francia;CHU Limoges,Limoges,France;CHU Limoges,Limoges,Francia;CHU Limoges,Limoges,Frankrijk;CHU Limoges,Limoges,França;CHU Limoges,Limoges,Франция ;CHU Limoges,Limoges,Frankrike
,
Adrien Chauchet
Affiliations:
CHU Besancon,Besancon,France;CHU Besancon,Besancon,Frankreich;CHU Besancon,Besancon,Francia;CHU Besancon,Besancon,France;CHU Besancon,Besancon,Francia;CHU Besancon,Besancon,Frankrijk;CHU Besancon,Besancon,França;CHU Besancon,Besancon,Франция ;CHU Besancon,Besancon,Frankrike
,
Laurianne Drieu La Rochelle
Affiliations:
CHU Tours,Tours,France;CHU Tours,Tours,Frankreich;CHU Tours,Tours,Francia;CHU Tours,Tours,France;CHU Tours,Tours,Francia;CHU Tours,Tours,Frankrijk;CHU Tours,Tours,França;CHU Tours,Tours,Франция ;CHU Tours,Tours,Frankrike
,
Jeremie Zerbit
Affiliations:
APHP Cochin,Paris,France;APHP Cochin,Paris,Frankreich;APHP Cochin,Paris,Francia;APHP Cochin,Paris,France;APHP Cochin,Paris,Francia;APHP Cochin,Paris,Frankrijk;APHP Cochin,Paris,França;APHP Cochin,Paris,Франция ;APHP Cochin,Paris,Frankrike
,
Olivier Hermine
Affiliations:
CHU Necker,Paris,France;CHU Necker,Paris,Frankreich;CHU Necker,Paris,Francia;CHU Necker,Paris,France;CHU Necker,Paris,Francia;CHU Necker,Paris,Frankrijk;CHU Necker,Paris,França;CHU Necker,Paris,Франция ;CHU Necker,Paris,Frankrike
,
Thomas Gastinne
Affiliations:
CHU Nantes,Nantes,France;CHU Nantes,Nantes,Frankreich;CHU Nantes,Nantes,Francia;CHU Nantes,Nantes,France;CHU Nantes,Nantes,Francia;CHU Nantes,Nantes,Frankrijk;CHU Nantes,Nantes,França;CHU Nantes,Nantes,Франция ;CHU Nantes,Nantes,Frankrike
,
Jean Jacques Tudesq
Affiliations:
CHU Montpellier,Montpellier,France;CHU Montpellier,Montpellier,Frankreich;CHU Montpellier,Montpellier,Francia;CHU Montpellier,Montpellier,France;CHU Montpellier,Montpellier,Francia;CHU Montpellier,Montpellier,Frankrijk;CHU Montpellier,Montpellier,França;CHU Montpellier,Montpellier,Франция ;CHU Montpellier,Montpellier,Frankrike
,
Elodie Gat
Affiliations:
LYSARC,Lyon,France;LYSARC,Lyon,Frankreich;LYSARC,Lyon,Francia;LYSARC,Lyon,France;LYSARC,Lyon,Francia;LYSARC,Lyon,Frankrijk;LYSARC,Lyon,França;LYSARC,Lyon,Франция ;LYSARC,Lyon,Frankrike
,
Florence Broussais
Affiliations:
LYSARC,Lyon,France;LYSARC,Lyon,Frankreich;LYSARC,Lyon,Francia;LYSARC,Lyon,France;LYSARC,Lyon,Francia;LYSARC,Lyon,Frankrijk;LYSARC,Lyon,França;LYSARC,Lyon,Франция ;LYSARC,Lyon,Frankrike
,
Catherine Thieblemont
Affiliations:
CHU Saint Louis,Paris,France;CHU Saint Louis,Paris,Frankreich;CHU Saint Louis,Paris,Francia;CHU Saint Louis,Paris,France;CHU Saint Louis,Paris,Francia;CHU Saint Louis,Paris,Frankrijk;CHU Saint Louis,Paris,França;CHU Saint Louis,Paris,Франция ;CHU Saint Louis,Paris,Frankrike
,
Roch Houot
Affiliations:
CHU Rennes,Rennes,France;CHU Rennes,Rennes,Frankreich;CHU Rennes,Rennes,Francia;CHU Rennes,Rennes,France;CHU Rennes,Rennes,Francia;CHU Rennes,Rennes,Frankrijk;CHU Rennes,Rennes,França;CHU Rennes,Rennes,Франция ;CHU Rennes,Rennes,Frankrike
Franck Morschhauser
Affiliations:
CHU Lille,Lille,France;CHU Lille,Lille,Frankreich;CHU Lille,Lille,Francia;CHU Lille,Lille,France;CHU Lille,Lille,Francia;CHU Lille,Lille,Frankrijk;CHU Lille,Lille,França;CHU Lille,Lille,Франция ;CHU Lille,Lille,Frankrike
(Abstract release date: 05/12/22) EHA Library. Bachy E. 06/11/22; 357124; S260
Emmanuel Bachy
Emmanuel Bachy
Contributions
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

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies