TY - JOUR
T1 - Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma
AU - Strati, Paolo
AU - Varma, Ankur
AU - Adkins, Sherry
AU - Nastoupil, Loretta J.
AU - Westin, Jason R.
AU - Hagemeister, Fredrick B
AU - Fowler, Nathan H.
AU - Lee, Hun J.
AU - Fayad, Luis E.
AU - Samaniego, Felipe
AU - Ahmed, Sairah
AU - Chen, Yiming
AU - Horowitz, Sandra
AU - Arafat, Sara
AU - Johncy, Swapna
AU - Kebriaei, Partow
AU - Mulanovich, Victor Eduardo
AU - Heredia, Ella Ariza
AU - Neelapu, Sattva S.
N1 - Funding Information:
This research is supported in part by the MD Anderson Cancer Center Support Grant P30 CA016672 and Kite Pharma. PS salary is supported by the Lymphoma Research Foundation Career Development Award. We thank Adrian Bot, John Rossi and Jenny Kim from Kite Pharma for data and manuscript review.
Publisher Copyright:
© 2021 Ferrata Storti Foundation
PY - 2021/10
Y1 - 2021/10
N2 - Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 may be associated with long-term adverse effects such as cytopenia and immune deficiency. In order to characterize these late events, we analyzed 31 patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel at our institution on two clinical trials, ZUMA-1 (clinicaltrials gov. Identifier: NCT02348216) and ZUMA-9 (clinicaltrials gov. Identifier: NCT03153462). Complete blood counts, lymphocyte subsets, and immunoglobulin levels were measured serially until month 24 or progression. Fifteen (48%) patients had grade 3-4 cytopenia, including anemia (five, 16%), neutropenia (nine, 29%), or thrombocytopenia (13, 42%) at day 30. Cytopenia at day 30 was not significantly associated with later diagnosis of myelodysplasia. Among patients with ongoing remission, grade 3-4 cytopenia was observed in one of nine (11%) at 2 years. While peripheral CD8+ T cells recovered early, CD4+ T-cell recovery was delayed with a count of <200/mL in three of nine (33%) patients at 1 year and two of seven (29%) at 2 years. Immunoglobulin G levels normalized in five of nine (56%) patients at 2 years. Thirteen (42%) patients developed grade 3-4 infectious complications, including herpes zoster and Pneumocystis jiroveci pneumonia. These results suggest the need for prolonged monitoring and prophylaxis against opportunistic infections in these patients, to improve the long-term safety of axicabtagene ciloleucel therapy.
AB - Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 may be associated with long-term adverse effects such as cytopenia and immune deficiency. In order to characterize these late events, we analyzed 31 patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel at our institution on two clinical trials, ZUMA-1 (clinicaltrials gov. Identifier: NCT02348216) and ZUMA-9 (clinicaltrials gov. Identifier: NCT03153462). Complete blood counts, lymphocyte subsets, and immunoglobulin levels were measured serially until month 24 or progression. Fifteen (48%) patients had grade 3-4 cytopenia, including anemia (five, 16%), neutropenia (nine, 29%), or thrombocytopenia (13, 42%) at day 30. Cytopenia at day 30 was not significantly associated with later diagnosis of myelodysplasia. Among patients with ongoing remission, grade 3-4 cytopenia was observed in one of nine (11%) at 2 years. While peripheral CD8+ T cells recovered early, CD4+ T-cell recovery was delayed with a count of <200/mL in three of nine (33%) patients at 1 year and two of seven (29%) at 2 years. Immunoglobulin G levels normalized in five of nine (56%) patients at 2 years. Thirteen (42%) patients developed grade 3-4 infectious complications, including herpes zoster and Pneumocystis jiroveci pneumonia. These results suggest the need for prolonged monitoring and prophylaxis against opportunistic infections in these patients, to improve the long-term safety of axicabtagene ciloleucel therapy.
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U2 - 10.3324/haematol.2020.254045
DO - 10.3324/haematol.2020.254045
M3 - Article
C2 - 32732355
AN - SCOPUS:85105265129
SN - 0390-6078
VL - 106
SP - 2667
EP - 2672
JO - Haematologica
JF - Haematologica
IS - 10
ER -