Multicenter development of a PET-based risk assessment tool for product-specific outcome prediction in large B-cell lymphoma patients undergoing CAR T-cell therapy
© 2023. The Author(s)..
PURPOSE: The emergence of chimeric antigen receptor (CAR) T-cell therapy fundamentally changed the management of individuals with relapsed and refractory large B-cell lymphoma (LBCL). However, real-world data have shown divergent outcomes for the approved products. The present study therefore set out to evaluate potential risk factors in a larger cohort.
METHODS: Our analysis set included 88 patients, treated in four German university hospitals and one Italian center, who had undergone 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET) before CAR T-cell therapy with tisagenlecleucel or axicabtagene ciloleucel. We first determined the predictive value of conventional risk factors, treatment lines, and response to bridging therapy for progression-free survival (PFS) through forward selection based on Cox regression. In a second step, the additive potential of two common PET parameters was assessed. Their optimal dichotomizing thresholds were calculated individually for each CAR T-cell product.
RESULTS: Extra-nodal involvement emerged as the most relevant of the conventional tumor and patient characteristics. Moreover, we found that inclusion of metabolic tumor volume (MTV) further improves outcome prediction. The hazard ratio for a PFS event was 1.68 per unit increase of our proposed risk score (95% confidence interval [1.20, 2.35], P = 0.003), which comprised both extra-nodal disease and lymphoma burden. While the most suitable MTV cut-off among patients receiving tisagenlecleucel was 11 mL, a markedly higher threshold of 259 mL showed optimal predictive performance in those undergoing axicabtagene ciloleucel treatment.
CONCLUSION: Our analysis demonstrates that the presence of more than one extra-nodal lesion and higher MTV in LBCL are associated with inferior outcome after CAR T-cell treatment. Based on an assessment tool including these two factors, patients can be assigned to one of three risk groups. Importantly, as shown by our study, metabolic tumor burden might facilitate CAR T-cell product selection and reflect the individual need for bridging therapy.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
|---|---|
| Enthalten in: |
European journal of nuclear medicine and molecular imaging - 51(2024), 5 vom: 21. März, Seite 1361-1370 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Voltin, Conrad-Amadeus [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
CAR T-cell therapy |
|---|
| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 24.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s00259-023-06554-0 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366052845 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366052845 | ||
| 003 | DE-627 | ||
| 005 | 20240324234918.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231227s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s00259-023-06554-0 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1344.xml |
| 035 | |a (DE-627)NLM366052845 | ||
| 035 | |a (NLM)38114616 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Voltin, Conrad-Amadeus |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Multicenter development of a PET-based risk assessment tool for product-specific outcome prediction in large B-cell lymphoma patients undergoing CAR T-cell therapy |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.03.2024 | ||
| 500 | |a Date Revised 24.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a PURPOSE: The emergence of chimeric antigen receptor (CAR) T-cell therapy fundamentally changed the management of individuals with relapsed and refractory large B-cell lymphoma (LBCL). However, real-world data have shown divergent outcomes for the approved products. The present study therefore set out to evaluate potential risk factors in a larger cohort | ||
| 520 | |a METHODS: Our analysis set included 88 patients, treated in four German university hospitals and one Italian center, who had undergone 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET) before CAR T-cell therapy with tisagenlecleucel or axicabtagene ciloleucel. We first determined the predictive value of conventional risk factors, treatment lines, and response to bridging therapy for progression-free survival (PFS) through forward selection based on Cox regression. In a second step, the additive potential of two common PET parameters was assessed. Their optimal dichotomizing thresholds were calculated individually for each CAR T-cell product | ||
| 520 | |a RESULTS: Extra-nodal involvement emerged as the most relevant of the conventional tumor and patient characteristics. Moreover, we found that inclusion of metabolic tumor volume (MTV) further improves outcome prediction. The hazard ratio for a PFS event was 1.68 per unit increase of our proposed risk score (95% confidence interval [1.20, 2.35], P = 0.003), which comprised both extra-nodal disease and lymphoma burden. While the most suitable MTV cut-off among patients receiving tisagenlecleucel was 11 mL, a markedly higher threshold of 259 mL showed optimal predictive performance in those undergoing axicabtagene ciloleucel treatment | ||
| 520 | |a CONCLUSION: Our analysis demonstrates that the presence of more than one extra-nodal lesion and higher MTV in LBCL are associated with inferior outcome after CAR T-cell treatment. Based on an assessment tool including these two factors, patients can be assigned to one of three risk groups. Importantly, as shown by our study, metabolic tumor burden might facilitate CAR T-cell product selection and reflect the individual need for bridging therapy | ||
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CAR T-cell therapy | |
| 650 | 4 | |a Extra-nodal involvement | |
| 650 | 4 | |a Large B-cell lymphoma | |
| 650 | 4 | |a MTV | |
| 650 | 4 | |a Risk factors | |
| 700 | 1 | |a Paccagnella, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Winkelmann, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Heger, Jan-Michel |e verfasserin |4 aut | |
| 700 | 1 | |a Casadei, Beatrice |e verfasserin |4 aut | |
| 700 | 1 | |a Beckmann, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Herrmann, Ken |e verfasserin |4 aut | |
| 700 | 1 | |a Dekorsy, Franziska J |e verfasserin |4 aut | |
| 700 | 1 | |a Kutsch, Nadine |e verfasserin |4 aut | |
| 700 | 1 | |a Borchmann, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Fanti, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Kunz, Wolfgang G |e verfasserin |4 aut | |
| 700 | 1 | |a Subklewe, Marion |e verfasserin |4 aut | |
| 700 | 1 | |a Kobe, Carsten |e verfasserin |4 aut | |
| 700 | 1 | |a Zinzani, Pier Luigi |e verfasserin |4 aut | |
| 700 | 1 | |a Stelljes, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Roth, Katrin S |e verfasserin |4 aut | |
| 700 | 1 | |a Drzezga, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Noppeney, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Rahbar, Kambiz |e verfasserin |4 aut | |
| 700 | 1 | |a Reinhardt, H Christian |e verfasserin |4 aut | |
| 700 | 1 | |a von Tresckow, Bastian |e verfasserin |4 aut | |
| 700 | 1 | |a Seifert, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Albring, Jörn C |e verfasserin |4 aut | |
| 700 | 1 | |a Blumenberg, Viktoria |e verfasserin |4 aut | |
| 700 | 1 | |a Farolfi, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Flossdorf, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Gödel, Philipp |e verfasserin |4 aut | |
| 700 | 1 | |a Hanoun, Christine |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of nuclear medicine and molecular imaging |d 2002 |g 51(2024), 5 vom: 21. März, Seite 1361-1370 |w (DE-627)NLM116957360 |x 1619-7089 |7 nnns |
| 773 | 1 | 8 | |g volume:51 |g year:2024 |g number:5 |g day:21 |g month:03 |g pages:1361-1370 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s00259-023-06554-0 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 51 |j 2024 |e 5 |b 21 |c 03 |h 1361-1370 | ||