Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia

Abstract

Flavopiridol, a cyclin-dependent kinase inhibitor, is cytotoxic to leukemic blasts. In a Phase II study, flavopiridol 50 mg/m(2) was given by 1-h infusion daily x 3 beginning day 1 followed by 2 g/m(2)/72 h ara-C beginning day 6 and 40 mg/m(2) mitoxantrone on day 9 (FLAM) to 45 adults with newly diagnosed acute myelogenous leukemia (AML) with multiple poor-risk features. Thirty patients (67%) achieved complete remission (CR) and 4 (9%) died. Twelve (40%) received myeloablative allogeneic bone marrow transplant (BMT) in first CR. Median OS and DFS are not reached (67% alive 12.5-31 months, 58% in CR 11.4-30 months), with median follow-up 22 months. Sixteen received FLAM in CR, with median OS and DFS 9 and 13.1 months, and 36% alive at 21-31 months. Short OS and DFS correlated with adverse cytogenetics, regardless of age or treatment in CR. The addition of allogeneic BMT in CR translates into long OS and DFS in the majority of eligible patients.

Figure 1

Overall survival (―) with confidence limits for all 45 patients receiving induction therapy with FLAM. Median overall survival for the entire group is 7.4 months.

Figure 2

Overall (―) and disease-free (---) survival for the 30 patients who achieved a complete remission. Median overall survival was 12.6 months and median disease-free survival was 13.3 months.

Figure 3

Overall and disease-free survival for the 30 complete remission patients, analyzed according to whether or not the patient underwent bone marrow transplantation (BMT) in CR. Median overall survival for 12 BMT patients (---) was not reached and for 18 non-BMT patients (―) was 10 months (p=0.06). Median disease-free survival for BMT patients was not reached and for non-BMT patients was 9 months (p=0.05).