PMID- 35316325
OWN - NLM
STAT- MEDLINE
DCOM- 20220801
LR  - 20220811
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 140
IP  - 4
DP  - 2022 Jul 28
TI  - GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell 
      lymphoma in Germany.
PG  - 349-358
LID - 10.1182/blood.2021015209 [doi]
AB  - CD19-directed chimeric antigen receptor (CAR) T cells have evolved as a new 
      standard-of-care (SOC) treatment in patients with relapsed/refractory (r/r) large 
      B-cell lymphoma (LBCL). Here, we report the first German real-world data on SOC 
      CAR T-cell therapies with the aim to explore risk factors associated with 
      outcomes. Patients who received SOC axicabtagene ciloleucel (axi-cel) or 
      tisagenlecleucel (tisa-cel) for LBCL and were registered with the German Registry 
      for Stem Cell Transplantation (DRST) were eligible. The main outcomes analyzed 
      were toxicities, response, overall survival (OS), and progression-free survival 
      (PFS). We report 356 patients who received axi-cel (n = 173) or tisa-cel (n = 
      183) between November 2018 and April 2021 at 21 German centers. Whereas the 
      axi-cel and tisa-cel cohorts were comparable for age, sex, lactate dehydrogenase 
      (LDH), international prognostic index (IPI), and pretreatment, the tisa-cel group 
      comprised significantly more patients with poor performance status, ineligibility 
      for ZUMA-1, and the need for bridging, respectively. With a median follow-up of 
      11 months, Kaplan-Meier estimates of OS, PFS, and nonrelapse mortality (NRM) 12 
      months after dosing were 52%, 30%, and 6%, respectively. While NRM was largely 
      driven by infections subsequent to prolonged neutropenia and/or severe 
      neurotoxicity and significantly higher with axi-cel, significant risk factors for 
      PFS on the multivariate analysis included bridging failure, elevated LDH, age, 
      and tisa-cel use. In conclusion, this study suggests that important outcome 
      determinants of CD19-directed CAR T-cell treatment of LBCL in the real-world 
      setting are bridging success, CAR-T product selection, LDH, and the absence of 
      prolonged neutropenia and/or severe neurotoxicity. These findings may have 
      implications for designing risk-adapted CAR T-cell therapy strategies.
CI  - (c) 2022 by The American Society of Hematology.
FAU - Bethge, Wolfgang A
AU  - Bethge WA
AUID- ORCID: 0000-0001-6052-2618
AD  - Department of Hematology and Oncology, University Hospital Tuebingen, Tuebingen, 
      Germany.
FAU - Martus, Peter
AU  - Martus P
AD  - Department of Biometrics and Statistics, University Hospital of Tuebingen, 
      Tuebingen, Germany.
FAU - Schmitt, Michael
AU  - Schmitt M
AD  - Department of Hematology and Oncology, University Hospital Heidelberg, 
      Heidelberg, Germany.
FAU - Holtick, Udo
AU  - Holtick U
AD  - Department of Hematology and Oncology, University Hospital Cologne, Cologne, 
      Germany.
FAU - Subklewe, Marion
AU  - Subklewe M
AUID- ORCID: 0000-0001-9154-9469
AD  - Department of Hematology and Oncology, University Hospital Munich (LMU Munich), 
      Munich, Germany.
FAU - von Tresckow, Bastian
AU  - von Tresckow B
AUID- ORCID: 0000-0003-1410-4487
AD  - Department of Hematology and Oncology, University Hospital Essen, Essen, Germany.
FAU - Ayuk, Francis
AU  - Ayuk F
AD  - Department for Stem Cell Transplantation, University Hospital Hamburg, Hamburg, 
      Germany.
FAU - Wagner-Drouet, Eva Marie
AU  - Wagner-Drouet EM
AUID- ORCID: 0000-0002-0728-2253
AD  - Department of Hematology and Oncology, University Hospital Mainz, Mainz, Germany.
FAU - Wulf, Gerald G
AU  - Wulf GG
AD  - Department of Hematology and Oncology, University Hospital Goettingen, Gottingen, 
      Germany.
FAU - Marks, Reinhard
AU  - Marks R
AD  - Department of Hematology and Oncology, University Hospital Freiburg, Freiburg, 
      Germany.
FAU - Penack, Olaf
AU  - Penack O
AD  - Department of Hematology and Oncology, University Hospital Charite Berlin, 
      Berlin, Germany.
FAU - Schnetzke, Ulf
AU  - Schnetzke U
AD  - Department of Hematology and Oncology, University Hospital Jena, Jena, Germany.
FAU - Koenecke, Christian
AU  - Koenecke C
AUID- ORCID: 0000-0001-7025-1735
AD  - Department of Hematology and Oncology, University Hospital Hannover, Hannover, 
      Germany.
FAU - von Bonin, Malte
AU  - von Bonin M
AD  - Department of Hematology and Oncology, University Hospital Dresden, Dresden, 
      Germany.
FAU - Stelljes, Matthias
AU  - Stelljes M
AUID- ORCID: 0000-0002-9331-5145
AD  - Department of Hematology and Oncology, University Hospital Muenster, Muenster, 
      Germany.
FAU - Glass, Bertram
AU  - Glass B
AD  - Department of Hematology and Oncology, Klinikum Berlin-Buch, Berlin, Germany.
FAU - Baldus, Claudia D
AU  - Baldus CD
AD  - Department of Hematology and Oncology, University Hospital Schleswig-Holstein, 
      Kiel, Germany.
FAU - Vucinic, Vladan
AU  - Vucinic V
AUID- ORCID: 0000-0002-8398-285X
AD  - University Hospital Leipzig, Leipzig, Germany.
FAU - Mougiakakos, Dimitrios
AU  - Mougiakakos D
AD  - Department of Hematology and Oncology, University Hospital Erlangen, Erlangen, 
      Germany.
FAU - Topp, Max
AU  - Topp M
AD  - Department of Hematology and Oncology, University Hospital Wuerzburg, Wuerzburg, 
      Germany.
FAU - Fante, Matthias A
AU  - Fante MA
AD  - Department of Hematology and Oncology, University Hospital Regensburg, 
      Regensburg, Germany; and.
FAU - Schroers, Roland
AU  - Schroers R
AUID- ORCID: 0000-0003-2744-5491
AD  - Department of Hematology and Oncology, University Hospital Bochum, Bochum, 
      Germany.
FAU - Bayir, Lale
AU  - Bayir L
AD  - Department of Hematology and Oncology, University Hospital Hannover, Hannover, 
      Germany.
FAU - Borchmann, Peter
AU  - Borchmann P
AD  - Department of Hematology and Oncology, University Hospital Cologne, Cologne, 
      Germany.
FAU - Buecklein, Veit
AU  - Buecklein V
AUID- ORCID: 0000-0001-7391-7280
AD  - Department of Hematology and Oncology, University Hospital Munich (LMU Munich), 
      Munich, Germany.
FAU - Hasenkamp, Justin
AU  - Hasenkamp J
AD  - Department of Hematology and Oncology, University Hospital Goettingen, Gottingen, 
      Germany.
FAU - Hanoun, Christine
AU  - Hanoun C
AD  - Department of Hematology and Oncology, University Hospital Essen, Essen, Germany.
FAU - Thomas, Simone
AU  - Thomas S
AD  - Department of Hematology and Oncology, University Hospital Regensburg, 
      Regensburg, Germany; and.
FAU - Beelen, Dietrich W
AU  - Beelen DW
AD  - Department of Hematology and Oncology, University Hospital Essen, Essen, Germany.
FAU - Lengerke, Claudia
AU  - Lengerke C
AUID- ORCID: 0000-0001-5442-2805
AD  - Department of Hematology and Oncology, University Hospital Tuebingen, Tuebingen, 
      Germany.
FAU - Kroeger, Nicolaus
AU  - Kroeger N
AD  - Department for Stem Cell Transplantation, University Hospital Hamburg, Hamburg, 
      Germany.
FAU - Dreger, Peter
AU  - Dreger P
AD  - Department of Hematology and Oncology, University Hospital Heidelberg, 
      Heidelberg, Germany.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD19)
SB  - IM
CIN - Blood. 2022 Jul 28;140(4):296-298. PMID: 35900785
MH  - Antigens, CD19
MH  - Germany/epidemiology
MH  - Humans
MH  - Immunotherapy, Adoptive/adverse effects
MH  - *Lymphoma, Large B-Cell, Diffuse/pathology
MH  - *Neutropenia/chemically induced
EDAT- 2022/03/23 06:00
MHDA- 2022/08/02 06:00
CRDT- 2022/03/22 17:17
PHST- 2021/12/20 00:00 [received]
PHST- 2022/03/09 00:00 [accepted]
PHST- 2022/03/23 06:00 [pubmed]
PHST- 2022/08/02 06:00 [medline]
PHST- 2022/03/22 17:17 [entrez]
AID - S0006-4971(22)00405-0 [pii]
AID - 10.1182/blood.2021015209 [doi]
PST - ppublish
SO  - Blood. 2022 Jul 28;140(4):349-358. doi: 10.1182/blood.2021015209.