Adding bortezomib (Velcade) to standard daunorubicin and cytarabine induction chemotherapy for acute myeloid leukemia (AML) “resulted in an encouraging remission rate” in previously untreated older adults, according to results of Cancer and Leukemia Group B (CALGB/Alliance) study 10502. The frequency of complete remission was 65% (62 of 95 patients), and 4% of patients achieved complete remission with incomplete platelet recovery. The researchers had found a similar remission frequency—61% complete remission rate and 10% rate of complete remission with incomplete platelet recovery—in a previous study of bortezomib added to induction therapy with idarubicin and cytarabine in patients with relapsed AML and older patients with de novo disease.
Patients in the current study were 60 to 75 years old and received bortezomib at 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin at 60 mg/m2 on days 1 through 3 and cytarabine at 100 mg/m2 by continuous IV infusion on days 1 through 7. Patients who achieved complete remission received up to two courses of consolidation chemotherapy with cytarabine at 2 g/m2 on days 1 through 5 with bortezomib, the researchers explained. Three dose levels of bortezomib (0.7, 1.0, and 1.3 mg/m2), were tested during consolidation therapy, with the highest dose proving tolerable.
The researchers had previously demonstrated that expression of CD74 “was associated with clinical outcome in patients with AML treated with bortezomib, idarubicin, and cytarabine,” and assessed the relationship in this study also. “Lower CD74 expression was associated with [complete remission/ complete remission with incomplete platelet recovery] (P = .04) but not with disease-free or overall survival,” the investigators stated. Median disease-free survival was 8 months, and median overall survival was 12 months.
Eleven patients developed grade 3 sensory neuropathy at some point during therapy. Neuropathy generally lessened or resolved with weeks of treatment, although several patients experienced persistent long-term grade 1 sensory neuropathy.”
“A phase III 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,” the researchers concluded.
Attar EC, et al: J Clin Oncol 31:923-929, 2013.