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CAR T-CELLS ASSOCIATED ACUTE TOXICITY IN B-CELL NON-HODGKIN LYMPHOMA: REAL-WORLD STUDY FROM THE DESCAR-T REGISTRY
Author(s): ,
PIERRE SESQUES
Affiliations:
CHU LYON SUD,LYON,France;CHU LYON SUD,LYON,Frankreich;CHU LYON SUD,LYON,Francia;CHU LYON SUD,LYON,France;CHU LYON SUD,LYON,Francia;CHU LYON SUD,LYON,Frankrijk;CHU LYON SUD,LYON,França;CHU LYON SUD,LYON,Франция ;CHU LYON SUD,LYON,Frankrike
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ROBERTA DI BLASI
Affiliations:
Hematology,Assistance Publique Hôpitaux de Paris ,PARIS,France;Hematology,Assistance Publique Hôpitaux de Paris ,PARIS,Frankreich;Hematology,Assistance Publique Hôpitaux de Paris ,PARIS,Francia;Hematology,Assistance Publique Hôpitaux de Paris ,PARIS,France;Hematology,Assistance Publique Hôpitaux de Paris ,PARIS,Francia;Hematology,Assistance Publique Hôpitaux de Paris ,PARIS,Frankrijk;Hematology,As
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STEVEN LE GOUILL
Affiliations:
Hematology,INSTITUT CURIE,PARIS,France;Hematology,INSTITUT CURIE,PARIS,Frankreich;Hematology,INSTITUT CURIE,PARIS,Francia;Hematology,INSTITUT CURIE,PARIS,France;Hematology,INSTITUT CURIE,PARIS,Francia;Hematology,INSTITUT CURIE,PARIS,Frankrijk;Hematology,INSTITUT CURIE,PARIS,França;Hematology,INSTITUT CURIE,PARIS,Франция ;Hematology,INSTITUT CURIE,PARIS,Frankrike
,
GUILLAUME CARTRON
Affiliations:
HEMATOLOGY,Département d'Hématologie clinique, CHU de Montpellier,MONTPELLIER,France;HEMATOLOGY,Département d'Hématologie clinique, CHU de Montpellier,MONTPELLIER,Frankreich;HEMATOLOGY,Département d'Hématologie clinique, CHU de Montpellier,MONTPELLIER,Francia;HEMATOLOGY,Département d'Hématologie clinique, CHU de Montpellier,MONTPELLIER,France;HEMATOLOGY,Département d'Hématologie clinique, CHU de M
,
GUILLAUME MANSON
Affiliations:
CHU de Rennes,RENNES,France;CHU de Rennes,RENNES,Frankreich;CHU de Rennes,RENNES,Francia;CHU de Rennes,RENNES,France;CHU de Rennes,RENNES,Francia;CHU de Rennes,RENNES,Frankrijk;CHU de Rennes,RENNES,França;CHU de Rennes,RENNES,Франция ;CHU de Rennes,RENNES,Frankrike
,
DAVID BEAUVAIS
Affiliations:
Hématologie clinique, CHU de Lille,LILLE,France;Hématologie clinique, CHU de Lille,LILLE,Frankreich;Hématologie clinique, CHU de Lille,LILLE,Francia;Hématologie clinique, CHU de Lille,LILLE,France;Hématologie clinique, CHU de Lille,LILLE,Francia;Hématologie clinique, CHU de Lille,LILLE,Frankrijk;Hématologie clinique, CHU de Lille,LILLE,França;Hématologie clinique, CHU de Lille,LILLE,Франция ;Hémat
,
FABIEN LE BRAS
Affiliations:
Lymphoid Malignancies,CRETEIL,France;Lymphoid Malignancies,CRETEIL,Frankreich;Lymphoid Malignancies,CRETEIL,Francia;Lymphoid Malignancies,CRETEIL,France;Lymphoid Malignancies,CRETEIL,Francia;Lymphoid Malignancies,CRETEIL,Frankrijk;Lymphoid Malignancies,CRETEIL,França;Lymphoid Malignancies,CRETEIL,Франция ;Lymphoid Malignancies,CRETEIL,Frankrike
,
FRANCOIS XAVIER GROS
Affiliations:
Hématologie Clinique et Thérapie cellulaire,MERIGNAC,France;Hématologie Clinique et Thérapie cellulaire,MERIGNAC,Frankreich;Hématologie Clinique et Thérapie cellulaire,MERIGNAC,Francia;Hématologie Clinique et Thérapie cellulaire,MERIGNAC,France;Hématologie Clinique et Thérapie cellulaire,MERIGNAC,Francia;Hématologie Clinique et Thérapie cellulaire,MERIGNAC,Frankrijk;Hématologie Clinique et Thérapi
,
SYLVAIN CHOQUET
Affiliations:
APHP la Pitié Salpêtriere,PARIS,France;APHP la Pitié Salpêtriere,PARIS,Frankreich;APHP la Pitié Salpêtriere,PARIS,Francia;APHP la Pitié Salpêtriere,PARIS,France;APHP la Pitié Salpêtriere,PARIS,Francia;APHP la Pitié Salpêtriere,PARIS,Frankrijk;APHP la Pitié Salpêtriere,PARIS,França;APHP la Pitié Salpêtriere,PARIS,Франция ;APHP la Pitié Salpêtriere,PARIS,Frankrike
,
PIERRE BORIES
Affiliations:
Hematology Laboratory, Onco-occitanie Network,TOULOUSE,France;Hematology Laboratory, Onco-occitanie Network,TOULOUSE,Frankreich;Hematology Laboratory, Onco-occitanie Network,TOULOUSE,Francia;Hematology Laboratory, Onco-occitanie Network,TOULOUSE,France;Hematology Laboratory, Onco-occitanie Network,TOULOUSE,Francia;Hematology Laboratory, Onco-occitanie Network,TOULOUSE,Frankrijk;Hematology Laborato
,
MARIE THERESE RUBIO
Affiliations:
Service Hématologie,NANCY,France;Service Hématologie,NANCY,Frankreich;Service Hématologie,NANCY,Francia;Service Hématologie,NANCY,France;Service Hématologie,NANCY,Francia;Service Hématologie,NANCY,Frankrijk;Service Hématologie,NANCY,França;Service Hématologie,NANCY,Франция ;Service Hématologie,NANCY,Frankrike
,
RENE OLIVIER CASASNOVAS
Affiliations:
Department of Hematology,DIJON,France;Department of Hematology,DIJON,Frankreich;Department of Hematology,DIJON,Francia;Department of Hematology,DIJON,France;Department of Hematology,DIJON,Francia;Department of Hematology,DIJON,Frankrijk;Department of Hematology,DIJON,França;Department of Hematology,DIJON,Франция ;Department of Hematology,DIJON,Frankrike
,
LAURA BOUNAIX
Affiliations:
Department of Hematology, Clermont-Ferrand University Hospital,CLEMRONT FERRAND,France;Department of Hematology, Clermont-Ferrand University Hospital,CLEMRONT FERRAND,Frankreich;Department of Hematology, Clermont-Ferrand University Hospital,CLEMRONT FERRAND,Francia;Department of Hematology, Clermont-Ferrand University Hospital,CLEMRONT FERRAND,France;Department of Hematology, Clermont-Ferrand Univ
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MOHAMAD MOHTY
Affiliations:
Hôpital St Antoine,PARIS,France;Hôpital St Antoine,PARIS,Frankreich;Hôpital St Antoine,PARIS,Francia;Hôpital St Antoine,PARIS,France;Hôpital St Antoine,PARIS,Francia;Hôpital St Antoine,PARIS,Frankrijk;Hôpital St Antoine,PARIS,França;Hôpital St Antoine,PARIS,Франция ;Hôpital St Antoine,PARIS,Frankrike
,
MAGALIE JORIS
Affiliations:
Hematology department, CHU Amiens,AMIENS,France;Hematology department, CHU Amiens,AMIENS,Frankreich;Hematology department, CHU Amiens,AMIENS,Francia;Hematology department, CHU Amiens,AMIENS,France;Hematology department, CHU Amiens,AMIENS,Francia;Hematology department, CHU Amiens,AMIENS,Frankrijk;Hematology department, CHU Amiens,AMIENS,França;Hematology department, CHU Amiens,AMIENS,Франция ;Hemat
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JULIE ABRAHAM
Affiliations:
CHU DE LIMOGES - HOPITAL DUPUYTREN,LIMOGES,France;CHU DE LIMOGES - HOPITAL DUPUYTREN,LIMOGES,Frankreich;CHU DE LIMOGES - HOPITAL DUPUYTREN,LIMOGES,Francia;CHU DE LIMOGES - HOPITAL DUPUYTREN,LIMOGES,France;CHU DE LIMOGES - HOPITAL DUPUYTREN,LIMOGES,Francia;CHU DE LIMOGES - HOPITAL DUPUYTREN,LIMOGES,Frankrijk;CHU DE LIMOGES - HOPITAL DUPUYTREN,LIMOGES,França;CHU DE LIMOGES - HOPITAL DUPUYTREN,LIMOGE
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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
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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
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SYLVAIN CARRAS
Affiliations:
CHU DE GRENOBLE,GRENOBLE,France;CHU DE GRENOBLE,GRENOBLE,Frankreich;CHU DE GRENOBLE,GRENOBLE,Francia;CHU DE GRENOBLE,GRENOBLE,France;CHU DE GRENOBLE,GRENOBLE,Francia;CHU DE GRENOBLE,GRENOBLE,Frankrijk;CHU DE GRENOBLE,GRENOBLE,França;CHU DE GRENOBLE,GRENOBLE,Франция ;CHU DE GRENOBLE,GRENOBLE,Frankrike
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ADRIEN CHAUCHET
Affiliations:
CHU JEAN MINJOZ,BESANCON,France;CHU JEAN MINJOZ,BESANCON,Frankreich;CHU JEAN MINJOZ,BESANCON,Francia;CHU JEAN MINJOZ,BESANCON,France;CHU JEAN MINJOZ,BESANCON,Francia;CHU JEAN MINJOZ,BESANCON,Frankrijk;CHU JEAN MINJOZ,BESANCON,França;CHU JEAN MINJOZ,BESANCON,Франция ;CHU JEAN MINJOZ,BESANCON,Frankrike
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LAURIANNE DRIEU LA ROCHELLE
Affiliations:
CHU BRETONNEAU,TOURS,France;CHU BRETONNEAU,TOURS,Frankreich;CHU BRETONNEAU,TOURS,Francia;CHU BRETONNEAU,TOURS,France;CHU BRETONNEAU,TOURS,Francia;CHU BRETONNEAU,TOURS,Frankrijk;CHU BRETONNEAU,TOURS,França;CHU BRETONNEAU,TOURS,Франция ;CHU BRETONNEAU,TOURS,Frankrike
,
JEREMIE ZERBIT
Affiliations:
APHP HOPITAL COCHIN,PARIS,France;APHP HOPITAL COCHIN,PARIS,Frankreich;APHP HOPITAL COCHIN,PARIS,Francia;APHP HOPITAL COCHIN,PARIS,France;APHP HOPITAL COCHIN,PARIS,Francia;APHP HOPITAL COCHIN,PARIS,Frankrijk;APHP HOPITAL COCHIN,PARIS,França;APHP HOPITAL COCHIN,PARIS,Франция ;APHP HOPITAL COCHIN,PARIS,Frankrike
,
OLIVIER HERMINE
Affiliations:
APHP HOPITAL NECKER,PARIS,France;APHP HOPITAL NECKER,PARIS,Frankreich;APHP HOPITAL NECKER,PARIS,Francia;APHP HOPITAL NECKER,PARIS,France;APHP HOPITAL NECKER,PARIS,Francia;APHP HOPITAL NECKER,PARIS,Frankrijk;APHP HOPITAL NECKER,PARIS,França;APHP HOPITAL NECKER,PARIS,Франция ;APHP HOPITAL NECKER,PARIS,Frankrike
,
STEPHANIE GUIDEZ
Affiliations:
CHU DE POITIERS - HOPITAL DE LA MILETRIE,POITIERS,France;CHU DE POITIERS - HOPITAL DE LA MILETRIE,POITIERS,Frankreich;CHU DE POITIERS - HOPITAL DE LA MILETRIE,POITIERS,Francia;CHU DE POITIERS - HOPITAL DE LA MILETRIE,POITIERS,France;CHU DE POITIERS - HOPITAL DE LA MILETRIE,POITIERS,Francia;CHU DE POITIERS - HOPITAL DE LA MILETRIE,POITIERS,Frankrijk;CHU DE POITIERS - HOPITAL DE LA MILETRIE,POITIERS
,
THOMAS GASTINNE
Affiliations:
Nantes University Hospital Clinical Hematology,NANTES,France;Nantes University Hospital Clinical Hematology,NANTES,Frankreich;Nantes University Hospital Clinical Hematology,NANTES,Francia;Nantes University Hospital Clinical Hematology,NANTES,France;Nantes University Hospital Clinical Hematology,NANTES,Francia;Nantes University Hospital Clinical Hematology,NANTES,Frankrijk;Nantes University Hospita
,
JEAN JACQUES TUDESQ
Affiliations:
Hematology Department, Montpellier University Hospital, Univ Montpellier,MONTPELLIER,France;Hematology Department, Montpellier University Hospital, Univ Montpellier,MONTPELLIER,Frankreich;Hematology Department, Montpellier University Hospital, Univ Montpellier,MONTPELLIER,Francia;Hematology Department, Montpellier University Hospital, Univ Montpellier,MONTPELLIER,France;Hematology Department, Mont
,
PATRICK FOGARTY
Affiliations:
biostatistics,LYSARC,LYON,France;biostatistics,LYSARC,LYON,Frankreich;biostatistics,LYSARC,LYON,Francia;biostatistics,LYSARC,LYON,France;biostatistics,LYSARC,LYON,Francia;biostatistics,LYSARC,LYON,Frankrijk;biostatistics,LYSARC,LYON,França;biostatistics,LYSARC,LYON,Франция ;biostatistics,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
,
FRANCK MORSCHHAUSER
Affiliations:
Maladies du Sang CHRU Lille,LILLE,France;Maladies du Sang CHRU Lille,LILLE,Frankreich;Maladies du Sang CHRU Lille,LILLE,Francia;Maladies du Sang CHRU Lille,LILLE,France;Maladies du Sang CHRU Lille,LILLE,Francia;Maladies du Sang CHRU Lille,LILLE,Frankrijk;Maladies du Sang CHRU Lille,LILLE,França;Maladies du Sang CHRU Lille,LILLE,Франция ;Maladies du Sang CHRU Lille,LILLE,Frankrike
,
ROCH HOUOT
Affiliations:
CHU de Rennes, Université de Rennes, INSERM U1236, EFS,RENNES,France;CHU de Rennes, Université de Rennes, INSERM U1236, EFS,RENNES,Frankreich;CHU de Rennes, Université de Rennes, INSERM U1236, EFS,RENNES,Francia;CHU de Rennes, Université de Rennes, INSERM U1236, EFS,RENNES,France;CHU de Rennes, Université de Rennes, INSERM U1236, EFS,RENNES,Francia;CHU de Rennes, Université de Rennes, INSERM U1236
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CATHERINE THIEBLEMONT
Affiliations:
Saint Louis Hospital,PARIS,France;Saint Louis Hospital,PARIS,Frankreich;Saint Louis Hospital,PARIS,Francia;Saint Louis Hospital,PARIS,France;Saint Louis Hospital,PARIS,Francia;Saint Louis Hospital,PARIS,Frankrijk;Saint Louis Hospital,PARIS,França;Saint Louis Hospital,PARIS,Франция ;Saint Louis Hospital,PARIS,Frankrike
EMMANUEL BACHY
Affiliations:
chu lyon sud,LYON,France;chu lyon sud,LYON,Frankreich;chu lyon sud,LYON,Francia;chu lyon sud,LYON,France;chu lyon sud,LYON,Francia;chu lyon sud,LYON,Frankrijk;chu lyon sud,LYON,França;chu lyon sud,LYON,Франция ;chu lyon sud,LYON,Frankrike
(Abstract release date: 05/12/22) EHA Library. Sesques P. 06/11/22; 357074; S210
Dr. Pierre Sesques
Dr. Pierre Sesques
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: S210

Type: Oral Presentation

Session title: Aggressive Lymphoma - CART

Background

Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are common immune-related toxicities associated with chimeric antigen receptor (CAR)–T-cell therapy. Their clinical manifestations can be severe and potentially life threatening.

Aims

Here, we report the French experience of CAR-T toxicity, we specifically addressed the modifiable risk factors for toxicity and we assessed management toxicity in real-world population.

Methods

We conducted a study in a large cohort of R/R aggressive B-cell lymphoma patients (pts) treated with commercial products. All data were collected through the French DESCAR-T registry. CRS/ICANS were graded prospectively (ASTCT grade scale). Regarding previously validated predictive score of CRS and ICANS in the literature, EASIX score (LDHxCreatinine/Platelets), modified-EASIX score (m-EASIX: CRPxCreatinine/Platelets) and simplified-EASIX score (s-EASIX: LDH/Platelets) (Pennisi et al., 2021) were assessed in our cohort.

Results

A total of 705 pts were included for the analysis of toxicity with a median follow-up of 12 months (range: 0.2-39). Notably, 74 pts (11%) pts had an ECOG/PS ≥ 2 before lymphodepletion. CRS of any grade occurred in 587 pts (83.3%) including 62 (10.5%) with grade 3 or higher (grade 3+). The median time from the infusion to the onset of CRS was 2 days (range: 0-34); the median time to resolution was 6 days (range: 1-30). ICANS of any grade occurred in 289 pts (41%) including 78 (27%) with grade 3+. The median time from the infusion to the onset was 6 days (range: 0-379); the median time to resolution was 7 days (range: 1-100). Most patients (94.5%) with ICANS had previously experienced CRS. Only 89 pts (29.9%) required admission to intensive care unit. Tocilizumab was the most common treatment for toxicity (411 pts, 68%) and 272 pts (45%) received corticosteroids. Interestingly, 38% of patients with CRS grade 1, 53 % with grade 2 and 65% with grade 3+ developed ICANS subsequently.

In multivariate analysis, the parameters which retained statistical significance to predict any CRS were Axi-cel ([OR] = 2.79, 95% CI 1.75-4.45; p <0.0001) and elevated LDH (>upper limit normal; [OR] = 1.69, 95% CI 1.03-1.63; p = 0.03). Bulky mass > 5 cm ([OR] = 2.95, 95% CI 1.60-5.45; p = 0.0005), age <65 years ([OR] = 0.42, 95% CI 0.20-0.86; p = 0.01) and higher s-EASIX score ([OR] = 1.38, 95% CI 1.15-1.67; p = 0.0005) increased the risk of developing grade 3+ CRS. Parameters which retained statistical significance to predict any ICANS were Axi-cel ([OR] = 3.95, 95% CI 2.57-6.06; p <0.0001), ECOG ≥2 ([OR] = 2.10, 95% CI 1.26-3.51; p= 0.004), age ≥65 ([OR] = 3.17, 95% CI 2.10-4.79; p <0.0001) and higher s-EASIX score ([OR] = 1.20, 95% CI 1.03-1.40; p= 0.01). Axi-cel ([OR] = 13.1, 95% CI 3.98-43.3; p <0.001), ECOG ≥2 ([OR] = 0.04, 95% CI 1.007-4.38; p= 0.04) and higher s-EASIX score ([OR] = 1.35, 95% CI 1.08-1.67; p= 0.0067) increased the risk of developing grade 3+ ICANS. No survival impact (OS and PFS) was detected for pts who experimented any grade or grade 3+ of ICANS or CRS (Figure 1). Importantly, cumulative dose and duration of tocilizumab or corticosteroids were not significantly associated with adverse PFS or OS.

Conclusion

In this large study, robust biological and clinical predictive factors of CRS and ICANS were identified. A propensity-score matched comparison of axi-cel and tisa-cel for toxicities will be performed for the EHA congress. Neither grade 3+ CRS, ICANS, nor Tocilizumab or corticosteroids use for CAR-T toxicity had negative impact on survival.

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

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: S210

Type: Oral Presentation

Session title: Aggressive Lymphoma - CART

Background

Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are common immune-related toxicities associated with chimeric antigen receptor (CAR)–T-cell therapy. Their clinical manifestations can be severe and potentially life threatening.

Aims

Here, we report the French experience of CAR-T toxicity, we specifically addressed the modifiable risk factors for toxicity and we assessed management toxicity in real-world population.

Methods

We conducted a study in a large cohort of R/R aggressive B-cell lymphoma patients (pts) treated with commercial products. All data were collected through the French DESCAR-T registry. CRS/ICANS were graded prospectively (ASTCT grade scale). Regarding previously validated predictive score of CRS and ICANS in the literature, EASIX score (LDHxCreatinine/Platelets), modified-EASIX score (m-EASIX: CRPxCreatinine/Platelets) and simplified-EASIX score (s-EASIX: LDH/Platelets) (Pennisi et al., 2021) were assessed in our cohort.

Results

A total of 705 pts were included for the analysis of toxicity with a median follow-up of 12 months (range: 0.2-39). Notably, 74 pts (11%) pts had an ECOG/PS ≥ 2 before lymphodepletion. CRS of any grade occurred in 587 pts (83.3%) including 62 (10.5%) with grade 3 or higher (grade 3+). The median time from the infusion to the onset of CRS was 2 days (range: 0-34); the median time to resolution was 6 days (range: 1-30). ICANS of any grade occurred in 289 pts (41%) including 78 (27%) with grade 3+. The median time from the infusion to the onset was 6 days (range: 0-379); the median time to resolution was 7 days (range: 1-100). Most patients (94.5%) with ICANS had previously experienced CRS. Only 89 pts (29.9%) required admission to intensive care unit. Tocilizumab was the most common treatment for toxicity (411 pts, 68%) and 272 pts (45%) received corticosteroids. Interestingly, 38% of patients with CRS grade 1, 53 % with grade 2 and 65% with grade 3+ developed ICANS subsequently.

In multivariate analysis, the parameters which retained statistical significance to predict any CRS were Axi-cel ([OR] = 2.79, 95% CI 1.75-4.45; p <0.0001) and elevated LDH (>upper limit normal; [OR] = 1.69, 95% CI 1.03-1.63; p = 0.03). Bulky mass > 5 cm ([OR] = 2.95, 95% CI 1.60-5.45; p = 0.0005), age <65 years ([OR] = 0.42, 95% CI 0.20-0.86; p = 0.01) and higher s-EASIX score ([OR] = 1.38, 95% CI 1.15-1.67; p = 0.0005) increased the risk of developing grade 3+ CRS. Parameters which retained statistical significance to predict any ICANS were Axi-cel ([OR] = 3.95, 95% CI 2.57-6.06; p <0.0001), ECOG ≥2 ([OR] = 2.10, 95% CI 1.26-3.51; p= 0.004), age ≥65 ([OR] = 3.17, 95% CI 2.10-4.79; p <0.0001) and higher s-EASIX score ([OR] = 1.20, 95% CI 1.03-1.40; p= 0.01). Axi-cel ([OR] = 13.1, 95% CI 3.98-43.3; p <0.001), ECOG ≥2 ([OR] = 0.04, 95% CI 1.007-4.38; p= 0.04) and higher s-EASIX score ([OR] = 1.35, 95% CI 1.08-1.67; p= 0.0067) increased the risk of developing grade 3+ ICANS. No survival impact (OS and PFS) was detected for pts who experimented any grade or grade 3+ of ICANS or CRS (Figure 1). Importantly, cumulative dose and duration of tocilizumab or corticosteroids were not significantly associated with adverse PFS or OS.

Conclusion

In this large study, robust biological and clinical predictive factors of CRS and ICANS were identified. A propensity-score matched comparison of axi-cel and tisa-cel for toxicities will be performed for the EHA congress. Neither grade 3+ CRS, ICANS, nor Tocilizumab or corticosteroids use for CAR-T toxicity had negative impact on survival.

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

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