TY  - JOUR
A1  - Topp, Max S.
A1  - van Meerten, Tom
A1  - Houot, Roch
A1  - Minnema, Monique C.
A1  - Bouabdallah, Krimo
A1  - Lugtenburg, Pieternella J.
A1  - Thieblemont, Catherine
A1  - Wermke, Martin
A1  - Song, Kevin W.
A1  - Avivi, Irit
A1  - Kuruvilla, John
A1  - Dührsen, Ulrich
A1  - Zheng, Yan
A1  - Vardhanabhuti, Saran
A1  - Dong, Jinghui
A1  - Bot, Adrian
A1  - Rossi, John M.
A1  - Plaks, Vicki
A1  - Sherman, Marika
A1  - Kim, Jenny J.
A1  - Kerber, Anne
A1  - Kersten, Marie José
T1  - Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B-cell lymphoma
JF  - British Journal of Haematology
N2  - Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). To reduce axi-cel–related toxicity, several exploratory safety management cohorts were added to ZUMA-1 (NCT02348216), the pivotal phase 1/2 study of axi-cel in refractory LBCL. Cohort 4 evaluated the rates and severity of cytokine release syndrome (CRS) and neurologic events (NEs) with earlier corticosteroid and tocilizumab use. Primary endpoints were incidence and severity of CRS and NEs. Patients received 2 × 106 anti-CD19 CAR T cells/kg after conditioning chemotherapy. Forty-one patients received axi-cel. Incidences of any-grade CRS and NEs were 93% and 61%, respectively (grade ≥ 3, 2% and 17%). There was no grade 4 or 5 CRS or NE. Despite earlier dosing, the cumulative cortisone-equivalent corticosteroid dose in patients requiring corticosteroid therapy was lower than that reported in the pivotal ZUMA-1 cohorts. With a median follow-up of 14·8 months, objective and complete response rates were 73% and 51%, respectively, and 51% of treated patients were in ongoing response. Earlier and measured use of corticosteroids and/or tocilizumab has the potential to reduce the incidence of grade ≥ 3 CRS and NEs in patients with R/R LBCL receiving axi-cel.
KW  - toxicity
KW  - large B-cell lymphoma
KW  - axi-cel
KW  - CAR T
KW  - corticosteroids
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258342
VL  - 195
IS  - 3
ER  - 
TY  - JOUR
A1  - Dimopoulos, Meletios A.
A1  - Weisel, Katja C.
A1  - Song, Kevin W.
A1  - Delforge, Michel
A1  - Karlin, Lionel
A1  - Goldschmidt, Hartmut
A1  - Moreau, Philippe
A1  - Banos, Anne
A1  - Oriol, Albert
A1  - Garderet, Laurent
A1  - Cavo, Michele
A1  - Ivanova, Valentina
A1  - Alegre, Adrian
A1  - Martinez-Lopez, Joaquin
A1  - Chen, Christine
A1  - Spencer, Andrew
A1  - Knop, Stefan
A1  - Bahlis, Nizar J.
A1  - Renner, Christoph
A1  - Yu, Xin
A1  - Hong, Kevin
A1  - Sternas, Lars
A1  - Jacques, Christian
A1  - Zaki, Mohamed H.
A1  - San Miguel, Jesus F.
T1  - Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone
JF  - Haematologica
N2  - Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P<0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P=0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del(17p) (4.6 versus 1.1 months; HR, 0.34; P < 0.001), t(4;14) (2.8 versus 1.9 months; HR, 0.49; P=0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P<0.001). Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or highdose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P=0.008) in patients with del(17p), 7.5 versus 4.9 months (HR, 1.12; P=0.761) in those with t(4;14), and 14.0 versus 9.0 months (HR, 0.85; P=0.380) in standard-risk subjects. The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2% versus 9.7%) and those with del(17p) (31.8% versus 4.3%), whereas it was similar in patients with t(4; 14) (15.9% versus 13.3%). The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma and del(17p) and/or t(4;14).
KW  - translocation
KW  - plus dexamethasone
KW  - deletion 17P
KW  - bortezomib
KW  - therapy
KW  - abnormalities
KW  - stem-cell transplantation
KW  - growth-factor receptor 3
KW  - high-risk cytogenetics
KW  - intergroupe francophone
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140349
VL  - 100
IS  - 10
SP  - 1327
EP  - 1333
ER  -