TY - JOUR
T1 - Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy
AU - Holland, Elizabeth M.
AU - Yates, Bonnie
AU - Ling, Alex
AU - Yuan, Constance M.
AU - Wang, Hao Wei
AU - Stetler-Stevenson, Maryalice
AU - LaLoggia, Michael
AU - Molina, John C.
AU - Lichtenstein, Daniel A.
AU - Lee, Daniel W.
AU - Ligon, John A.
AU - Shalabi, Haneen
AU - Ahlman, Mark A.
AU - Shah, Nirali N.
N1 - Publisher Copyright:
© 2022 American Society of Hematology. All rights reserved.
PY - 2022/4/12
Y1 - 2022/4/12
N2 - Chimeric antigen receptor (CAR) T cells effectively eradicate medullary B-cell acute lymphoblastic leukemia (B-ALL) and can traffic to and clear central nervous system (CNS) involvement. CAR T-cell activity in non-CNS extramedullary disease (EMD) has not been well characterized. We systematically evaluated CAR T-cell kinetics, associated toxicities, and efficacy in B-ALL non-CNS EMD. We conducted a retrospective review of B-ALL patients with non-CNS EMD who were screened for/enrolled on one of three CAR trials (CD19, CD22, and CD19/22) at our institution. Non-CNS EMD was identified according to histology or radiographic imaging at extramedullary sites excluding the cerebrospinal fluid and CNS parenchyma. Of ∼180 patients with relapsed/refractory B-ALL screened across multiple early-phase trials over an 8-year period, 38 (21.1%) presented with isolated non-CNS EMD (n 5 5) or combined medullary/non-CNS EMD (n 5 33) on 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging. A subset receiving CAR T cells (18 infusions) obtained FDG PET/CT scans preinfusion and postinfusion to monitor response. At best response, 72.2% (13 of 18) of patients showed a medullary minimal residual disease–negative complete remission and complete (n 5 7) or partial (n 5 6) non-CNS EMD response. Non-CNS EMD responses to CAR T cells were delayed (n 5 3), and residual non-CNS EMD was substantial; rarely, discrepant outcomes (marrow response without EMD response) were observed (n 5 2). Unique CAR-associated toxicities at non-CNS EMD sites were seen in select patients. CAR T cells are active in B-ALL non-CNS EMD. Still, non-CNS EMD response to CAR T cells may be delayed and suboptimal, particularly with multifocal disease. Serial FDG PET/CT scans are necessary for identifying and monitoring non-CNS EMD.
AB - Chimeric antigen receptor (CAR) T cells effectively eradicate medullary B-cell acute lymphoblastic leukemia (B-ALL) and can traffic to and clear central nervous system (CNS) involvement. CAR T-cell activity in non-CNS extramedullary disease (EMD) has not been well characterized. We systematically evaluated CAR T-cell kinetics, associated toxicities, and efficacy in B-ALL non-CNS EMD. We conducted a retrospective review of B-ALL patients with non-CNS EMD who were screened for/enrolled on one of three CAR trials (CD19, CD22, and CD19/22) at our institution. Non-CNS EMD was identified according to histology or radiographic imaging at extramedullary sites excluding the cerebrospinal fluid and CNS parenchyma. Of ∼180 patients with relapsed/refractory B-ALL screened across multiple early-phase trials over an 8-year period, 38 (21.1%) presented with isolated non-CNS EMD (n 5 5) or combined medullary/non-CNS EMD (n 5 33) on 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging. A subset receiving CAR T cells (18 infusions) obtained FDG PET/CT scans preinfusion and postinfusion to monitor response. At best response, 72.2% (13 of 18) of patients showed a medullary minimal residual disease–negative complete remission and complete (n 5 7) or partial (n 5 6) non-CNS EMD response. Non-CNS EMD responses to CAR T cells were delayed (n 5 3), and residual non-CNS EMD was substantial; rarely, discrepant outcomes (marrow response without EMD response) were observed (n 5 2). Unique CAR-associated toxicities at non-CNS EMD sites were seen in select patients. CAR T cells are active in B-ALL non-CNS EMD. Still, non-CNS EMD response to CAR T cells may be delayed and suboptimal, particularly with multifocal disease. Serial FDG PET/CT scans are necessary for identifying and monitoring non-CNS EMD.
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UR - http://www.scopus.com/inward/citedby.url?scp=85128305183&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2021006035
DO - 10.1182/bloodadvances.2021006035
M3 - Article
C2 - 34920453
AN - SCOPUS:85128305183
SN - 2473-9529
VL - 6
SP - 2167
EP - 2182
JO - Blood Advances
JF - Blood Advances
IS - 7
ER -