TMTV CORRELATES WITH EARLY PROGRESSION (EP) AFTER CD19 CAR T-CELL THERAPY IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (R/R DLBCL)
Author(s): ,
Sophie Bernard
Affiliations:
Hematology unit,Hopital Saint Louis,Paris ,France
,
Laetitia Vercellino
Affiliations:
Nuclear medicine unit,St Louis Hospital ,Paris ,France
,
Caroline Bodet-Millin
Affiliations:
Nuclear medicine unit,CHU Hotel Dieu,Nantes ,France
,
Sylvie Chevret
Affiliations:
Biostatistics ,Hopital Saint Louis,Paris ,France
,
Salim Kanoun
Affiliations:
Nuclear medicine ,IUCT Oncopole ,Toulouse,France
,
Thomas Gastinne
Affiliations:
Hematology unit,CHU ,Nantes ,France
,
Roberta Di Blasi
Affiliations:
Hematology unit,Hopital Saint Louis,Paris ,France
,
Eugenio Galli
Affiliations:
Hematology unit,Hopital Saint Louis,Paris ,France
,
Francoise Kraeber-Bodéré
Affiliations:
Nuclear medicine ,CHU ,Nantes ,France
,
Benoit Tessoulin
Affiliations:
Hematology unit,CHU Nantes ,Nantes ,France
,
Hannah Moatti
Affiliations:
Hematology unit,Hopital Saint Louis,Paris ,France
,
Loic Ysebaert
Affiliations:
Hematology unit,IUCT Oncopole ,Toulouse,France
,
Steven Le Gouill
Affiliations:
Hematology unit,CHU Nantes ,Nantes ,France
Catherine Thieblemont
Affiliations:
Hematology unit,Hopital Saint Louis,Paris ,France
EHA Library. Bernard S. 06/12/20; 293989; EP1504
Dr. Sophie Bernard
Dr. Sophie Bernard
Contributions
Abstract

Abstract: EP1504

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
Despite significant clinical benefit in relapsed/refractory DLBCL, patients (pts) treated with autologous anti-CD19 chimeric antigen receptor (CD19 CAR) T-cells may experience early progression (EP) within the first 90 days after infusion. This highlights the importance of identifying predictive biomarkers. Total metabolic tumor volume (TMTV) measured with 18F-FDG PET/CT before R-CHOP is significantly associated with the outcome of pts with DLBCL de novo.

Aims
The aim of our study was to evaluate if high TMTV measured immediately before infusion was associated with EP in pts with R/R DLBCL treated with CAR T-cells.

Methods
We performed a cohort analysis including consecutive 102 pts treated with CAR T-cells (Axicabtagene or Tisagenlecleucel) for R/R DLBCL in 3 centers (Hospital Saint Louis Paris – Toulouse and Nantes) between June 2018 and January 2020. Median follow-up post injection was 155 days (range: 8-544). TMTV was measured on pre-infusion PET/CT with usual SUVmax threshold methods using the free semiautomatic software Beth Israel Fiji20 (St Louis-Paris) (http://petctviewer.org) and Dosisoft software (Nantes). Two methods to determine the TMTV were used: the thresholding method at 41% of the SUVmax (TMTV41%) and a fixed threshold of SUV> 4 (TMTVSUV4). Very EP and EP were determined based on the Lugano criteria determined before 30 days and before 90 days, respectively. The cumulative incidence of early relapse was estimated using the Kaplan-Meier method due to absence of competing death. Predictive factors associated with EP were assessed using univariate (10% level) then multivariate Cox models. All biological measurements were log-transformed for more symmetric distributions and an interpretable hazard ratio (HR) of EP according to the biomarker value. To measure the predictive accuracy of TMVT for progression, cumulative / dynamic ROC curves were used.

Results

102 pts received CD19 CAR T-cells (59 pts with Axicabtagene / 43 pts with Tisagenlecleucel). This abstract presents the results of the first 88 pts analysis.  The median age was 59 years (range: 22-77), with 82, 7 and 11 (2 unknown) pts having R/R DLBCL, primary mediastinal B-cell lymphoma and transformed follicular lymphoma, respectively; 74% were refractory to their last therapy, and 27% had prior autologous stem cell transplantation. An IPI score 3-5 was reported in 38% of pts. Median TMTV41% was 49.8 cm3 (range: 1.4-3247). Very EP and EP occurred in 18 pts and in 29 pts, respectively, within a median time of 28 days (range 6-88), while 8 pts additionally relapsed after from day 90 to day 181. High IPI (p< 0.001) and aaIPI=3 (p<0.001), C-reactive protein (CRP) (p<0.0001), ferritin (p=0.078), low albumin (p<0.0001), high lactate dehydrogenase (p=0.09), more intense SUVmax (p<0.001) and TMTV SUV4 (p<0.0001) were significantly associated with EP by univariate analyses. By multivariate analysis, TMTV SUV4 (HR=3.04, 95%CI [1.82; 5.08], p<0.0001) and aaIPI 3(HR=4.73, 95%CI [1.92;11.64], p=0.0007) were the only independent predictors of EP. Updated data with all patients will be presented at the meeting. 

Conclusion
In our cohort, pre-infusion TMVT was significantly correlated with early progression in patients with R/R DLBCL treated with CD19 CAR T-cells.

Session topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical

Keyword(s): CAR-T, DLBCL, PET, Relapsed lymphoma

Abstract: EP1504

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
Despite significant clinical benefit in relapsed/refractory DLBCL, patients (pts) treated with autologous anti-CD19 chimeric antigen receptor (CD19 CAR) T-cells may experience early progression (EP) within the first 90 days after infusion. This highlights the importance of identifying predictive biomarkers. Total metabolic tumor volume (TMTV) measured with 18F-FDG PET/CT before R-CHOP is significantly associated with the outcome of pts with DLBCL de novo.

Aims
The aim of our study was to evaluate if high TMTV measured immediately before infusion was associated with EP in pts with R/R DLBCL treated with CAR T-cells.

Methods
We performed a cohort analysis including consecutive 102 pts treated with CAR T-cells (Axicabtagene or Tisagenlecleucel) for R/R DLBCL in 3 centers (Hospital Saint Louis Paris – Toulouse and Nantes) between June 2018 and January 2020. Median follow-up post injection was 155 days (range: 8-544). TMTV was measured on pre-infusion PET/CT with usual SUVmax threshold methods using the free semiautomatic software Beth Israel Fiji20 (St Louis-Paris) (http://petctviewer.org) and Dosisoft software (Nantes). Two methods to determine the TMTV were used: the thresholding method at 41% of the SUVmax (TMTV41%) and a fixed threshold of SUV> 4 (TMTVSUV4). Very EP and EP were determined based on the Lugano criteria determined before 30 days and before 90 days, respectively. The cumulative incidence of early relapse was estimated using the Kaplan-Meier method due to absence of competing death. Predictive factors associated with EP were assessed using univariate (10% level) then multivariate Cox models. All biological measurements were log-transformed for more symmetric distributions and an interpretable hazard ratio (HR) of EP according to the biomarker value. To measure the predictive accuracy of TMVT for progression, cumulative / dynamic ROC curves were used.

Results

102 pts received CD19 CAR T-cells (59 pts with Axicabtagene / 43 pts with Tisagenlecleucel). This abstract presents the results of the first 88 pts analysis.  The median age was 59 years (range: 22-77), with 82, 7 and 11 (2 unknown) pts having R/R DLBCL, primary mediastinal B-cell lymphoma and transformed follicular lymphoma, respectively; 74% were refractory to their last therapy, and 27% had prior autologous stem cell transplantation. An IPI score 3-5 was reported in 38% of pts. Median TMTV41% was 49.8 cm3 (range: 1.4-3247). Very EP and EP occurred in 18 pts and in 29 pts, respectively, within a median time of 28 days (range 6-88), while 8 pts additionally relapsed after from day 90 to day 181. High IPI (p< 0.001) and aaIPI=3 (p<0.001), C-reactive protein (CRP) (p<0.0001), ferritin (p=0.078), low albumin (p<0.0001), high lactate dehydrogenase (p=0.09), more intense SUVmax (p<0.001) and TMTV SUV4 (p<0.0001) were significantly associated with EP by univariate analyses. By multivariate analysis, TMTV SUV4 (HR=3.04, 95%CI [1.82; 5.08], p<0.0001) and aaIPI 3(HR=4.73, 95%CI [1.92;11.64], p=0.0007) were the only independent predictors of EP. Updated data with all patients will be presented at the meeting. 

Conclusion
In our cohort, pre-infusion TMVT was significantly correlated with early progression in patients with R/R DLBCL treated with CD19 CAR T-cells.

Session topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical

Keyword(s): CAR-T, DLBCL, PET, Relapsed lymphoma

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