TY - JOUR
T1 - Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies
AU - Jain, Tania
AU - Knezevic, Andrea
AU - Pennisi, Martina
AU - Chen, Yunxin
AU - Ruiz, Josel D.
AU - Purdon, Terence J.
AU - Devlin, Sean M.
AU - Smith, Melody
AU - Shah, Gunjan L.
AU - Halton, Elizabeth
AU - Diamonte, Claudia
AU - Scordo, Michael
AU - Sauter, Craig S.
AU - Mead, Elena
AU - Santomasso, Bianca D.
AU - Palomba, M. Lia
AU - Batlevi, Connie W.
AU - Maloy, Molly A.
AU - Giralt, Sergio
AU - Smith, Eric
AU - Brentjens, Renier
AU - Park, Jae H.
AU - Perales, Miguel Angel
AU - Mailankody, Sham
N1 - Funding Information:
This work was supported by National Institutes of Health, National Cancer Institute Cancer Center Support Grant P30 CA008748 (to Memorial Sloan Kettering Cancer Center).
Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/8/11
Y1 - 2020/8/11
N2 - Factors contributing to hematopoietic recovery following chimeric antigen receptor (CAR) T-cell therapy have not been well studied. In an analysis of 83 patients with hematologic malignancies treated with CAR T-cell therapy, we describe patterns of hematopoietic recovery and evaluate potentially associated factors. We included patients who received axicabtagene ciloleucel (n = 30) or tisagenlecleucel (n = 10) for B-cell lymphoma, CD19-28z CAR T therapy for B-cell acute lymphoblastic leukemia (NCT01044069; n = 37), or B-cell maturation antigen targeting CAR T cells for multiple myeloma (NCT03070327; n = 6). Patients treated with CAR T cells who had not progressed, died, or received additional chemotherapy had "recovered"(per definition in Materials and methods section) hemoglobin, platelet, neutrophil, and white blood cell counts at rates of 61%, 51%, 33%, and 28% at month 1 postinfusion and 93%, 90%, 80%, and 59% at month 3 postinfusion, respectively. Univariate analysis showed that increasing grade of immune effector cell-associated neurological syndrome (ICANS), baseline cytopenias, CAR construct, and higher peak C-reactive protein or ferritin levels were statistically significantly associated with a lower likelihood of complete count recovery at 1 month; a similar trend was seen for cytokine release syndrome (CRS). After adjustment for baseline cytopenia and CAR construct, grade ≥3 CRS or ICANS remained significantly associated with the absence of complete count recovery at 1 month. Higher levels of vascular endothelial growth factor and macrophage-derived chemokines, although not statistically significant, were seen patients without complete count recovery at 1 month. This remains to be studied further in larger prospective studies.
AB - Factors contributing to hematopoietic recovery following chimeric antigen receptor (CAR) T-cell therapy have not been well studied. In an analysis of 83 patients with hematologic malignancies treated with CAR T-cell therapy, we describe patterns of hematopoietic recovery and evaluate potentially associated factors. We included patients who received axicabtagene ciloleucel (n = 30) or tisagenlecleucel (n = 10) for B-cell lymphoma, CD19-28z CAR T therapy for B-cell acute lymphoblastic leukemia (NCT01044069; n = 37), or B-cell maturation antigen targeting CAR T cells for multiple myeloma (NCT03070327; n = 6). Patients treated with CAR T cells who had not progressed, died, or received additional chemotherapy had "recovered"(per definition in Materials and methods section) hemoglobin, platelet, neutrophil, and white blood cell counts at rates of 61%, 51%, 33%, and 28% at month 1 postinfusion and 93%, 90%, 80%, and 59% at month 3 postinfusion, respectively. Univariate analysis showed that increasing grade of immune effector cell-associated neurological syndrome (ICANS), baseline cytopenias, CAR construct, and higher peak C-reactive protein or ferritin levels were statistically significantly associated with a lower likelihood of complete count recovery at 1 month; a similar trend was seen for cytokine release syndrome (CRS). After adjustment for baseline cytopenia and CAR construct, grade ≥3 CRS or ICANS remained significantly associated with the absence of complete count recovery at 1 month. Higher levels of vascular endothelial growth factor and macrophage-derived chemokines, although not statistically significant, were seen patients without complete count recovery at 1 month. This remains to be studied further in larger prospective studies.
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U2 - 10.1182/bloodadvances.2020002509
DO - 10.1182/bloodadvances.2020002509
M3 - Article
C2 - 32780846
AN - SCOPUS:85090556703
SN - 2473-9529
VL - 4
SP - 3776
EP - 3787
JO - Blood Advances
JF - Blood Advances
IS - 15
ER -