Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance)

• Published in: Blood advances Vol. 5; no. 13; pp. 2775 - 2787
• Main Authors: Walker, Alison R., Marcucci, Guido, Yin, Jun, Blum, William, Stock, Wendy, Kohlschmidt, Jessica, Mrózek, Krzysztof, Carroll, Andrew J., Eisfeld, Ann-Kathrin, Wang, Eunice S., Jacobson, Sawyer, Kolitz, Jonathan E., Thakuri, Mohan, Sutamtewagul, Grerk, Vij, Ravi, Stuart, Robert K., Byrd, John C., Bloomfield, Clara D., Stone, Richard M., Larson, Richard A.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 13.07.2021; American Society of Hematology
• Subjects: Clinical Trials and Observations
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2021004233

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/m2 per day on days 4-10) and daunorubicin (60 mg/m2 per day on days 4-6) followed by cytarabine consolidation (2000 mg/m2 per day on days 4-8) with (arm A) or without (arm B) G3139 (7 mg/m2 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. •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. [Display omitted]