Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study.
Aged
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Agents, Immunological
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Decitabine
/ administration & dosage
Drug Monitoring
Female
Humans
Kaplan-Meier Estimate
Leukemia, Myeloid, Acute
/ drug therapy
Male
Middle Aged
Prognosis
Research Design
Treatment Outcome
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
24
07
2019
accepted:
13
02
2020
revised:
11
12
2019
pubmed:
24
3
2020
medline:
14
1
2021
entrez:
24
3
2020
Statut:
ppublish
Résumé
Talacotuzumab, a humanized anti-CD123 monoclonal antibody, was evaluated in combination with decitabine in elderly patients with acute myeloid leukemia (AML) not eligible for intensive chemotherapy. A multicenter, phase 2/3 study was initiated to determine the recommended phase 2 dose (RP2D) of talacotuzumab (Part A) followed by an open-label, randomized comparison of talacotuzumab in combination with decitabine versus decitabine alone to assess achievement of complete response (CR) and overall survival (OS) in Part B. Ten patients were enrolled in Part A and 316 in Part B; the results presented here are based on a database lock on January 25, 2018. Part A confirmed the RP2D of talacotuzumab to be 9 mg/kg. In Part B, CR was achieved in 12/80 (15%) patients receiving combination therapy and in 9/82 (11%) patients receiving decitabine alone (odds ratio: 1.4; 95% confidence interval [CI]: 0.6-3.6; p = 0.44). Median (95% CI) OS was 5.36 (4.27-7.95) months for combination therapy versus 7.26 (6.47-8.64) months for decitabine alone (hazard ratio: 1.04; 95% CI: 0.79-1.37; p = 0.78). Combination therapy showed no improvement in efficacy versus decitabine alone, resulting in the Independent Data Monitoring Committee's recommendation of early termination of enrollment and discontinuation of talacotuzumab treatment.
Identifiants
pubmed: 32203138
doi: 10.1038/s41375-020-0773-5
pii: 10.1038/s41375-020-0773-5
pmc: PMC7787975
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
Decitabine
776B62CQ27
Types de publication
Clinical Trial, Phase II
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
62-74Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
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