TY  - JOUR
A1  - Kiem, Dominik
A1  - Leisch, Michael
A1  - Neureiter, Daniel
A1  - Haslauer, Theresa
A1  - Egle, Alexander
A1  - Melchardt, Thomas
A1  - Topp, Max S.
A1  - Greil, Richard
T1  - Two cases of pancytopenia with Coombs-negative hemolytic anemia after chimeric antigen receptor T-cell therapy
JF  - International Journal of Molecular Sciences
N2  - Background: Chimeric antigen receptor (CAR) T-cells are changing the therapeutic landscape of hematologic malignancies. Severe side effects include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but prolonged cytopenia has also been reported. The underlying mechanism for prolonged cytopenia is poorly understood so far. Cases: Severe pancytopenia with grade 2-3 anemia was marked 2–3 months after treatment. Laboratory evaluation revealed undetectable levels of haptoglobin with increased reticulocyte counts. Coomb's tests were negative, no schistocytes were detected on blood smear, and infectious causes were ruled out. Increased erythropoiesis without lymphoma infiltration was noted on bone marrow biopsy. A spontaneous increase in haptoglobin and hemoglobin levels was observed after several weeks. For one patient, peripheral CAR-T levels were monitored over time. We observed a decline at the same time as hemoglobin levels began to rise, implying a potential causality. Conclusion: To our knowledge, we describe the first two cases of Coombs-negative hemolytic anemia after CAR-T treatment for B-cell lymphoma. We encourage routine monitoring for hemolytic anemia after CAR-T treatment and also encourage further investigations on the underlying mechanism.
KW  - CAR T-cell
KW  - hemolytic anemia
KW  - prolonged cytopenia
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284977
SN  - 1422-0067
VL  - 22
IS  - 11
ER  - 
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  -