Journal article
Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance)
Blood advances, Vol.5(13), pp.2775-2787
07/12/2021
DOI: 10.1182/bloodadvances.2021004233
PMCID: PMC8288671
PMID: 34251414
Abstract
G3139 can be safely added to conventional chemotherapy for older patients with AML.
Adding G3139 did not improve complete remission rates, but patients with secondary AML had improved DFS.
Overexpression of B-cell leukemia/lymphoma 2 (BCL2) renders acute myeloid leukemia (AML) cells resistant to chemotherapy and has been associated with unfavorable outcomes. Oblimersen (G3139) is a phosphorothioate 18-mer antisense oligonucleotide directed against the first 6
BCL2
codons. In a phase 1 study of AML patients treated with G3139, cytarabine, and daunorubicin induction with cytarabine consolidation, no antisense-related toxicity was reported, and BCL2 downregulation occurred in patients achieving complete remission. In this phase 3 trial, untreated older AML patients were randomized to cytarabine (100 mg/m
2
per day on days 4-10) and daunorubicin (60 mg/m
2
per day on days 4-6) followed by cytarabine consolidation (2000 mg/m
2
per day on days 4-8) with (arm A) or without (arm B) G3139 (7 mg/m
2
per day on days 1-10 [induction] or days 1-8 [consolidation]). A total of 506 patients were enrolled. No differences in toxicity were observed between arms. Estimated overall survival (OS) at 1 year was 43% for arm A and 40% for arm B (1-sided log rank
P
= .13), with no differences in disease-free (DFS;
P
= .26) or event-free survival (
P
= .80). Subgroup analyses showed patients age <70 years in arm A had improved OS by 1 month vs those in arm B (
P
= .04), and patients with secondary AML in arm A had better DFS vs those in arm B (
P
= .04). We conclude that addition of G3139 to chemotherapy failed to improve outcomes of older AML patients. However, more effective means of inhibiting BCL2 are showing promising results in combination with chemotherapy in AML. This trial was registered at
www.clinicaltrials.gov
as #NCT00085124.
Details
- Title: Subtitle
- Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance)
- Creators
- Alison R. Walker - The Ohio State UniversityGuido Marcucci - City Of Hope National Medical CenterJun Yin - Mayo ClinicWilliam Blum - Emory UniversityWendy Stock - University of ChicagoJessica Kohlschmidt - The Ohio State UniversityKrzysztof Mrózek - Sylvester Comprehensive Cancer CenterAndrew J. Carroll - University of Alabama at BirminghamAnn-Kathrin Eisfeld - The Ohio State UniversityEunice S. Wang - Roswell Park Cancer InstituteSawyer Jacobson - Mayo ClinicJonathan E. Kolitz - Hofstra UniversityMohan Thakuri - Cancer Care of Western North CarolinaGrerk Sutamtewagul - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IARavi Vij - Washington University in St. LouisRobert K. Stuart - MUSC Hollings Cancer CenterJohn C. Byrd - The Ohio State UniversityClara D. Bloomfield - The Ohio State UniversityRichard M. Stone - Dana-Farber Cancer InstituteRichard A. Larson - University of Chicago
- Resource Type
- Journal article
- Publication Details
- Blood advances, Vol.5(13), pp.2775-2787
- DOI
- 10.1182/bloodadvances.2021004233
- PMID
- 34251414
- PMCID
- PMC8288671
- NLM abbreviation
- Blood Adv
- ISSN
- 2473-9529
- eISSN
- 2473-9537
- Publisher
- American Society of Hematology
- Language
- English
- Date published
- 07/12/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Biostatistics; Internal Medicine
- Record Identifier
- 9984359881602771
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