Several factors that predict the outcome of large B‐cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T‐cell therapy can be identified before cell administration
Abstract Aim The aim of this study was to analyse the outcomes of patients with large B‐cell lymphoma (LBCL) treated with chimeric antigen receptor T‐cell therapy (CAR‐Tx), with a focus on outcomes after CAR T‐cell failure, and to define the risk factors for rapid progression and further treatment....
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-09-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.70138 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825206479071739904 |
|---|---|
| author | Alice Sýkorová František Folber Kamila Polgárová Heidi Móciková Juraj Ďuraš Kateřina Steinerová Aleš Obr Adriana Heindorfer Miriam Ladická Ľubica Lukáčová Erika Čellárová Ivana Plameňová David Belada Andrea Janíková Marek Trněný Tereza Jančárková Vít Procházka Andrej Vranovský Margaréta Králiková Jan Vydra Lukáš Smolej Ľuboš Drgoňa Martin Sedmina Eva Čermáková Robert Pytlík |
| author_facet | Alice Sýkorová František Folber Kamila Polgárová Heidi Móciková Juraj Ďuraš Kateřina Steinerová Aleš Obr Adriana Heindorfer Miriam Ladická Ľubica Lukáčová Erika Čellárová Ivana Plameňová David Belada Andrea Janíková Marek Trněný Tereza Jančárková Vít Procházka Andrej Vranovský Margaréta Králiková Jan Vydra Lukáš Smolej Ľuboš Drgoňa Martin Sedmina Eva Čermáková Robert Pytlík |
| author_sort | Alice Sýkorová |
| collection | DOAJ |
| description | Abstract Aim The aim of this study was to analyse the outcomes of patients with large B‐cell lymphoma (LBCL) treated with chimeric antigen receptor T‐cell therapy (CAR‐Tx), with a focus on outcomes after CAR T‐cell failure, and to define the risk factors for rapid progression and further treatment. Methods We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd‐line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. Results The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression‐free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty‐three patients (59%) were refractory or relapsed after CAR‐Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow‐up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR‐Tx. Risk factors for not receiving further therapy after CAR‐Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS‐2 (from R/P after CAR‐Tx) was 6.7 months (6‐month 57.9%) for treated patients and 0.4 months (6‐month 4.2%) for untreated patients (p < 0.001). The median PFS‐2 (from R/P after CAR‐Tx) was 3.2 months (6‐month 28.5%) for treated patients. The risk factors for a shorter PFS‐2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS‐2 for treated patients. Conclusion Our findings allow better stratification of CAR‐Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement). |
| format | Article |
| id | doaj-art-613627563fa145bcad4718e937c66eed |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-613627563fa145bcad4718e937c66eed2025-02-07T09:08:08ZengWileyCancer Medicine2045-76342024-09-011317n/an/a10.1002/cam4.70138Several factors that predict the outcome of large B‐cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T‐cell therapy can be identified before cell administrationAlice Sýkorová0František Folber1Kamila Polgárová2Heidi Móciková3Juraj Ďuraš4Kateřina Steinerová5Aleš Obr6Adriana Heindorfer7Miriam Ladická8Ľubica Lukáčová9Erika Čellárová10Ivana Plameňová11David Belada12Andrea Janíková13Marek Trněný14Tereza Jančárková15Vít Procházka16Andrej Vranovský17Margaréta Králiková18Jan Vydra19Lukáš Smolej20Ľuboš Drgoňa21Martin Sedmina22Eva Čermáková23Robert Pytlík244th Department of Internal Medicine – Haematology University Hospital and Faculty of Medicine Hradec Králové Czech RepublicDepartment of Internal Medicine, Haematology and Oncology Masaryk University Hospital Brno Czech Republic1st Department of Medicine‐Department of Haematology Charles University, General University Hospital Prague Czech RepublicDepartment of Haematology University Hospital Královské Vinohrady and Third Faculty of Medicine, Charles University Prague Czech RepublicDepartment of Haemato‐oncology University Hospital Ostrava and Faculty of Medicine, University of Ostrava Ostrava Czech RepublicDepartment of Haematology and Oncology University Hospital Pilsen Czech RepublicDepartment of Haemato‐Oncology, Faculty of Medicine and Dentistry Palacky University Olomouc Czech RepublicDepartment of Haematology Hospital Liberec Liberec Czech RepublicClinic of Oncohaematology Medical Faculty of Comenius University and National Cancer Institute Bratislava SlovakiaOncology Clinic J.A. Reiman Faculty Hospital Prešov SlovakiaDepartment of Haematology F.D. Roosevelt University Hospital Banská Bystrica SlovakiaClinic of Haematology and Transfusion Medicine Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava Martin Slovakia4th Department of Internal Medicine – Haematology University Hospital and Faculty of Medicine Hradec Králové Czech RepublicDepartment of Internal Medicine, Haematology and Oncology Masaryk University Hospital Brno Czech Republic1st Department of Medicine‐Department of Haematology Charles University, General University Hospital Prague Czech RepublicDepartment of Haematology University Hospital Královské Vinohrady and Third Faculty of Medicine, Charles University Prague Czech RepublicDepartment of Haemato‐Oncology, Faculty of Medicine and Dentistry Palacky University Olomouc Czech RepublicClinic of Oncohaematology Medical Faculty of Comenius University and National Cancer Institute Bratislava SlovakiaDepartment of Haematology F.D. Roosevelt University Hospital Banská Bystrica SlovakiaInstitute of Haematology and Blood Transfusion Prague Czech Republic4th Department of Internal Medicine – Haematology University Hospital and Faculty of Medicine Hradec Králové Czech RepublicClinic of Oncohaematology Medical Faculty of Comenius University and National Cancer Institute Bratislava SlovakiaDepartment of Haematology F.D. Roosevelt University Hospital Banská Bystrica SlovakiaDepartment of Medical Biophysics, Faculty of Medicine in Hradec Kralove Charles University Hradec Kralove Czech RepublicInstitute of Haematology and Blood Transfusion Prague Czech RepublicAbstract Aim The aim of this study was to analyse the outcomes of patients with large B‐cell lymphoma (LBCL) treated with chimeric antigen receptor T‐cell therapy (CAR‐Tx), with a focus on outcomes after CAR T‐cell failure, and to define the risk factors for rapid progression and further treatment. Methods We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd‐line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. Results The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression‐free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty‐three patients (59%) were refractory or relapsed after CAR‐Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow‐up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR‐Tx. Risk factors for not receiving further therapy after CAR‐Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS‐2 (from R/P after CAR‐Tx) was 6.7 months (6‐month 57.9%) for treated patients and 0.4 months (6‐month 4.2%) for untreated patients (p < 0.001). The median PFS‐2 (from R/P after CAR‐Tx) was 3.2 months (6‐month 28.5%) for treated patients. The risk factors for a shorter PFS‐2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS‐2 for treated patients. Conclusion Our findings allow better stratification of CAR‐Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement).https://doi.org/10.1002/cam4.70138CAR T‐cell failureoutcomes of patients after CAR T‐cell therapy failurerelapsed/refractory large B‐cell lymphomarisk factors for CAR T‐cell therapy failure |
| spellingShingle | Alice Sýkorová František Folber Kamila Polgárová Heidi Móciková Juraj Ďuraš Kateřina Steinerová Aleš Obr Adriana Heindorfer Miriam Ladická Ľubica Lukáčová Erika Čellárová Ivana Plameňová David Belada Andrea Janíková Marek Trněný Tereza Jančárková Vít Procházka Andrej Vranovský Margaréta Králiková Jan Vydra Lukáš Smolej Ľuboš Drgoňa Martin Sedmina Eva Čermáková Robert Pytlík Several factors that predict the outcome of large B‐cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T‐cell therapy can be identified before cell administration Cancer Medicine CAR T‐cell failure outcomes of patients after CAR T‐cell therapy failure relapsed/refractory large B‐cell lymphoma risk factors for CAR T‐cell therapy failure |
| title | Several factors that predict the outcome of large B‐cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T‐cell therapy can be identified before cell administration |
| title_full | Several factors that predict the outcome of large B‐cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T‐cell therapy can be identified before cell administration |
| title_fullStr | Several factors that predict the outcome of large B‐cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T‐cell therapy can be identified before cell administration |
| title_full_unstemmed | Several factors that predict the outcome of large B‐cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T‐cell therapy can be identified before cell administration |
| title_short | Several factors that predict the outcome of large B‐cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T‐cell therapy can be identified before cell administration |
| title_sort | several factors that predict the outcome of large b cell lymphoma patients who relapse progress after chimeric antigen receptor car t cell therapy can be identified before cell administration |
| topic | CAR T‐cell failure outcomes of patients after CAR T‐cell therapy failure relapsed/refractory large B‐cell lymphoma risk factors for CAR T‐cell therapy failure |
| url | https://doi.org/10.1002/cam4.70138 |
| work_keys_str_mv | AT alicesykorova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT frantisekfolber severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT kamilapolgarova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT heidimocikova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT jurajduras severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT katerinasteinerova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT alesobr severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT adrianaheindorfer severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT miriamladicka severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT lubicalukacova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT erikacellarova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT ivanaplamenova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT davidbelada severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT andreajanikova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT marektrneny severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT terezajancarkova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT vitprochazka severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT andrejvranovsky severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT margaretakralikova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT janvydra severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT lukassmolej severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT lubosdrgona severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT martinsedmina severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT evacermakova severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration AT robertpytlik severalfactorsthatpredicttheoutcomeoflargebcelllymphomapatientswhorelapseprogressafterchimericantigenreceptorcartcelltherapycanbeidentifiedbeforecelladministration |