Phase III Alliance Trial: Oblimersen for Older Patients With AML
Posted: Monday, August 23, 2021
Successful downregulation of BCL2 using the BCL2 antisense oligodeoxynucleotide oblimersen has previously been demonstrated in a phase I study of patients with acute myeloid leukemia (AML). However, although it was found to be safely tolerated, oblimersen did not appear to improve clinical outcomes in untreated older adults with AML, according to the multicenter CALGB 10201 (Alliance) phase III study.
“We conclude that addition of oblimersen 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,” stated Richard A. Larson, MD, of the University of Chicago Comprehensive Cancer Center, and colleagues. The findings of this study were published in the journal Blood Advances.
Patients aged 60 years and older with AML and no history of chemotherapy were enrolled (n = 506). Patients were randomly assigned to one of two arms. Patients in arm A received continuous intravenous infusions of oblimersen for 4 days prior to standard chemotherapy, and bone marrow biopsies were performed on day 17. Patients in arm B received standard chemotherapy alone with yoked doses, schedules, and methods of administration, but with bone marrow biopsies performed on day 14. Patients with residual leukemia received a second induction course.
No differences in toxicity were observed between the arms, and there appeared to be no differences in estimated overall survival at 1 year for arm A (43%) or arm B (40%, P = .13). Further, the addition of oblimersen did not seem to alter disease-free survival (P = .26) or event-free survival (P = .80). However, patients with secondary AML and patients younger than age 70 who received oblimersen exhibited improved disease-free survival (P = .04) and slightly improved overall survival (P = .04), respectively.
“Although there has been no further development of oblimersen, the concept of attacking antiapoptotic proteins, as attempted in the current trial, may represent a new paradigm in AML therapy,” stated the study authors.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
