A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia
© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved..
ABSTRACT: The curative potential of allogeneic hematopoietic transplantation (allo-HCT) in patients with acute lymphoblastic leukemia (ALL) is hampered by relapse. Inotuzumab ozogamicin (INO) is an anti-CD22 monoclonal antibody bound to calicheamicin, which has significant activity against ALL. We hypothesized that low-dose INO would be safe and feasible after allo-HCT. Therefore, we conducted a phase 1 study to determine the dose and safety in this setting. Patients were eligible if they were aged 16 to 75 years, had undergone allo-HCT for CD22+ ALL, were in complete remission (CR) after allo-HCT, had high risk of recurrence, were between day 40 and 100 after allo-HCT with adequate graft function, and did not have a history of sinusoidal obstruction syndrome (SOS). The objectives of this trial were to define INO maximum tolerated dose (MTD), to determine post-allo-HCT INO safety, and to measure 1-year progression-free survival (PFS). The trial design followed a "3+3" model. The treatment consisted of INO given on day 1 of 28-day cycles. Dose levels were 0.3 mg/m2, 0.4 mg/m2, 0.5 mg/m2, and 0.6 mg/m2. Median age was 44 years (range, 17-66 years; n = 18). Disease status at transplantation was first CR (n = 14) or second CR or beyond (n = 4). Preparative regimen was of reduced intensity in 72% of patients who received transplantation. Most common toxicity was thrombocytopenia. There were no instances of SOS; the MTD was 0.6 mg/m2. One-year nonrelapse mortality was 5.6%. With a median follow-up of 18.1 months (range, 8.6-59 months) 1-year post-allo-HCT PFS and overall survival is 89% and 94%, respectively. Low-dose INO has a favorable safety profile and was associated with high rates of 1-year PFS. This trial was registered at www.clinicaltrials.gov as #NCT03104491.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Blood advances - 8(2024), 6 vom: 26. März, Seite 1384-1391 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Metheny, Leland L [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal, Humanized |
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| Anmerkungen: |
Date Completed 14.03.2024 Date Revised 20.03.2024 published: Print ClinicalTrials.gov: NCT03104491 Citation Status MEDLINE |
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| doi: |
10.1182/bloodadvances.2023011514 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 2 | |a A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia |
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| 500 | |a ClinicalTrials.gov: NCT03104491 | ||
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| 520 | |a ABSTRACT: The curative potential of allogeneic hematopoietic transplantation (allo-HCT) in patients with acute lymphoblastic leukemia (ALL) is hampered by relapse. Inotuzumab ozogamicin (INO) is an anti-CD22 monoclonal antibody bound to calicheamicin, which has significant activity against ALL. We hypothesized that low-dose INO would be safe and feasible after allo-HCT. Therefore, we conducted a phase 1 study to determine the dose and safety in this setting. Patients were eligible if they were aged 16 to 75 years, had undergone allo-HCT for CD22+ ALL, were in complete remission (CR) after allo-HCT, had high risk of recurrence, were between day 40 and 100 after allo-HCT with adequate graft function, and did not have a history of sinusoidal obstruction syndrome (SOS). The objectives of this trial were to define INO maximum tolerated dose (MTD), to determine post-allo-HCT INO safety, and to measure 1-year progression-free survival (PFS). The trial design followed a "3+3" model. The treatment consisted of INO given on day 1 of 28-day cycles. Dose levels were 0.3 mg/m2, 0.4 mg/m2, 0.5 mg/m2, and 0.6 mg/m2. Median age was 44 years (range, 17-66 years; n = 18). Disease status at transplantation was first CR (n = 14) or second CR or beyond (n = 4). Preparative regimen was of reduced intensity in 72% of patients who received transplantation. Most common toxicity was thrombocytopenia. There were no instances of SOS; the MTD was 0.6 mg/m2. One-year nonrelapse mortality was 5.6%. With a median follow-up of 18.1 months (range, 8.6-59 months) 1-year post-allo-HCT PFS and overall survival is 89% and 94%, respectively. Low-dose INO has a favorable safety profile and was associated with high rates of 1-year PFS. This trial was registered at www.clinicaltrials.gov as #NCT03104491 | ||
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Inotuzumab Ozogamicin |2 NLM | |
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| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 700 | 1 | |a Sobecks, Ronald |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Pingfu |e verfasserin |4 aut | |
| 700 | 1 | |a Margevicius, Seunghee |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jiasheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ciarrone, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Kopp, Shelby |e verfasserin |4 aut | |
| 700 | 1 | |a Convents, Robin D |e verfasserin |4 aut | |
| 700 | 1 | |a Majhail, Navneet |e verfasserin |4 aut | |
| 700 | 1 | |a Caimi, Paolo F |e verfasserin |4 aut | |
| 700 | 1 | |a Otegbeye, Folashade |e verfasserin |4 aut | |
| 700 | 1 | |a Cooper, Brenda W |e verfasserin |4 aut | |
| 700 | 1 | |a Gallogly, Molly |e verfasserin |4 aut | |
| 700 | 1 | |a Malek, Ehsan |e verfasserin |4 aut | |
| 700 | 1 | |a Tomlinson, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Gerds, Aaron T |e verfasserin |4 aut | |
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| 700 | 1 | |a Perales, Miguel-Angel |e verfasserin |4 aut | |
| 700 | 1 | |a de Lima, Marcos |e verfasserin |4 aut | |
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