Adding Bortezomib to Induction, Consolidation Regimens Promising for Untreated AML in Older Patients
Noting that remission induction chemotherapy with cytarabine and an anthracycline has been a standard treatment for newly diagnosed AML for more than 30 years and that the complete remission rate for patients age ≥60 years is 40% to 60%, Eyal C. Attar, MD, Massachusetts General Hospital Cancer Center, Boston, MA, and colleagues investigated whether the addition of bortezomib could improve this remission rate with minimal added toxicity. They also examined the safety of bortezomib when combined with intermediate-dose cytarabine (Int-DAC) consolidation chemotherapy.
A total of 95 adults with previously untreated AML received bortezomib 1.3mg/m2 intravenously on days 1, 4, 8, and 11 with daunorubicin 60 mg/m2 on days 1 through 3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1 through 7. Median age of the patients was 67 years (range, 60 to 75 years).
Those who achieved complete remission received up to two courses of consolidation chemotherapy with cytarabine 2gm/m2 on days 1 through 5 with bortezomib. Escalating dose levels of bortezomib—0.7, 1.0, and 1.3 mg/m2—were tested in three cohorts. Dose-limiting toxicities were assessed during the first consolidation cycles and the relationship between cell surface CD74 expression and clinical outcome assessed.
Of the 95 patients, 62 (65%) achieved a complete remission and 4 (4%) a complete remission with incomplete platelet recovery. Grade 3 sensory neuropathy was observed in 11 patients.
“Bortezomib plus Int-DAC proved tolerable at the highest dose tested,” they found. Lower expression of CD74 was found to be associated with complete remission and complete remission with incomplete platelet recovery (P=0.04), but not with disease-free or overall survival.
“A phase 3 study in which patients are randomly assigned to receive bortezomib or a double-blinded placebo would be required to define the specific clinical benefit of bortezomib with induction and consolidation chemotherapy,” Dr. Attar concluded.