A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia Journal Article
| Authors: | Metheny, L. L.; Sobecks, R.; Cho, C.; Fu, P.; Margevicius, S.; Wang, J.; Ciarrone, L.; Kopp, S.; Convents, R. D.; Majhail, N.; Caimi, P. F.; Otegbeye, F.; Cooper, B. W.; Gallogly, M.; Malek, E.; Tomlinson, B.; Gerds, A. T.; Hamilton, B.; Giralt, S.; Perales, M. A.; de Lima, M. |
| Article Title: | A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia |
| 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. © 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International. |
| Journal Title: | Blood Advances |
| Volume: | 8 |
| Issue: | 6 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2024-03-26 |
| Start Page: | 1384 |
| End Page: | 1391 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2023011514 |
| PUBMED: | 38170741 |
| PROVIDER: | scopus |
| PMCID: | PMC10945150 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
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