Reinfusion of CD19 CAR T Cells for Relapse Prevention and Treatment in Children with Acute Lymphoblastic Leukemia
Copyright © 2024 American Society of Hematology..
Relapse after CD19-directed chimeric antigen receptor (CAR)-modified T-cells remains a substantial challenge. Short CAR T-cell persistence contributes to relapse risk, necessitating novel approaches to prolong durability. CAR T-cell reinfusion (CARTr) represents a potential strategy to reduce the risk of, or treat, relapsed disease after initial CAR infusion (CARTi). We conducted a retrospective review of reinfusion of murine (CTL019) or humanized (huCART19) anti-CD19.4-1BB CAR T-cells across 3 clinical trials or commercial tisagenlecleucel for relapse prevention [peripheral B-cell recovery (BCR) or bone marrow hematogones ≤6 months after CARTi], minimal residual disease (MRD) or relapse, or nonresponse to CARTi. The primary endpoint was complete response (CR) at day 28 after CARTr, defined as complete remission with B-cell aplasia. Of 262 primary treatments, 81 were followed by ≥1 reinfusion (investigational CTL019, n=44; huCART19, n=26; tisagenlecleucel, n=11), representing 79 unique patients. Of 63 reinfusions for relapse prevention, 52% achieved CR (BCR, 15/40, 38%; hematogones, 18/23, 78%). Lymphodepletion was associated with response to CARTr for BCR (OR 33.57, P = 0.015), but not hematogones (OR 0.30, P = 0.291). The cumulative incidence of relapse was 29% at 24-months for CR versus 61% for nonresponse to CARTr (P=0.259). For MRD/relapse, CR rate to CARTr was 50% (5/10), but 0/8 for nonresponse to CARTi. Toxicity was generally mild, with the only grade ≥3 cytokine release syndrome (n=6) or neurotoxicity (n=1) observed in MRD/relapse treatment. Reinfusion of CTL019/tisagenlecleucel or huCART19 is safe, may reduce relapse risk in a subset of patients, and can reinduce remission in CD19-positive relapse.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Blood advances - (2024) vom: 22. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Myers, Regina M [VerfasserIn] |
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| Anmerkungen: |
Date Revised 22.02.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1182/bloodadvances.2024012885 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368769933 |
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| 520 | |a Copyright © 2024 American Society of Hematology. | ||
| 520 | |a Relapse after CD19-directed chimeric antigen receptor (CAR)-modified T-cells remains a substantial challenge. Short CAR T-cell persistence contributes to relapse risk, necessitating novel approaches to prolong durability. CAR T-cell reinfusion (CARTr) represents a potential strategy to reduce the risk of, or treat, relapsed disease after initial CAR infusion (CARTi). We conducted a retrospective review of reinfusion of murine (CTL019) or humanized (huCART19) anti-CD19.4-1BB CAR T-cells across 3 clinical trials or commercial tisagenlecleucel for relapse prevention [peripheral B-cell recovery (BCR) or bone marrow hematogones ≤6 months after CARTi], minimal residual disease (MRD) or relapse, or nonresponse to CARTi. The primary endpoint was complete response (CR) at day 28 after CARTr, defined as complete remission with B-cell aplasia. Of 262 primary treatments, 81 were followed by ≥1 reinfusion (investigational CTL019, n=44; huCART19, n=26; tisagenlecleucel, n=11), representing 79 unique patients. Of 63 reinfusions for relapse prevention, 52% achieved CR (BCR, 15/40, 38%; hematogones, 18/23, 78%). Lymphodepletion was associated with response to CARTr for BCR (OR 33.57, P = 0.015), but not hematogones (OR 0.30, P = 0.291). The cumulative incidence of relapse was 29% at 24-months for CR versus 61% for nonresponse to CARTr (P=0.259). For MRD/relapse, CR rate to CARTr was 50% (5/10), but 0/8 for nonresponse to CARTi. Toxicity was generally mild, with the only grade ≥3 cytokine release syndrome (n=6) or neurotoxicity (n=1) observed in MRD/relapse treatment. Reinfusion of CTL019/tisagenlecleucel or huCART19 is safe, may reduce relapse risk in a subset of patients, and can reinduce remission in CD19-positive relapse | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Devine, Kaitlin J |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yimei |e verfasserin |4 aut | |
| 700 | 1 | |a Lawrence, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Barz Leahy, Allison |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Vernau, Lauren |e verfasserin |4 aut | |
| 700 | 1 | |a Callahan, Colleen |e verfasserin |4 aut | |
| 700 | 1 | |a Baniewicz, Diane |e verfasserin |4 aut | |
| 700 | 1 | |a Kadauke, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a McGuire, Regina |e verfasserin |4 aut | |
| 700 | 1 | |a Wertheim, Gerald |e verfasserin |4 aut | |
| 700 | 1 | |a Kulikovskaya, Irina |e verfasserin |4 aut | |
| 700 | 1 | |a Gonzalez, Vanessa |e verfasserin |4 aut | |
| 700 | 1 | |a Fraietta, Joseph A |e verfasserin |4 aut | |
| 700 | 1 | |a DiNofia, Amanda |e verfasserin |4 aut | |
| 700 | 1 | |a Hunger, Stephen P |e verfasserin |4 aut | |
| 700 | 1 | |a Rheingold, Susan R |e verfasserin |4 aut | |
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| 700 | 1 | |a June, Carl H |e verfasserin |4 aut | |
| 700 | 1 | |a Grupp, Stephan A |e verfasserin |4 aut | |
| 700 | 1 | |a Wray, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Maude, Shannon L |e verfasserin |4 aut | |
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