Treatment of older patients with de novo acute myeloid leukemia (AML) with one or more postremission chemotherapy courses: Analysis of four CALGB studies.

Abstract

6531 Background: AML in older patients is rarely cured by chemotherapy, but treatment is given to induce complete remission (CR) and prolong disease-free and overall survival (DFS, OS). Optimal post-CR chemotherapy has not been defined. We analyzed outcomes in previously untreated de novo AML patients ≥ 60 years (n = 1,525) among 4 consecutive CALGB trials using different consolidation regimens. A randomized trial (8923) produced similar results using 2 courses of cytarabine (AraC) 1 g/m2 x 5 days plus mitoxantrone 10 mg/m2 x 3 days compared to 4 courses of AraC at 100 mg/m2 x 5 days (Blood 2001;98:548). CALGB 9720 used ADE induction (AraC 100 mg/m2, daunorubicin 60 mg/m2 and etoposide 100 mg/m2 for 7, 3 and 3 days) with only a single post-remission course of the same drugs and doses for 5, 2 and 2 days. Methods: Results of 9720 were compared with results from similar patient populations treated on 3 other CALGB trials that used more than one post-CR course – either 4 courses (8525, 8923) or 2 intensified courses (8923, 10201). Results: The CR rate on 9720 did not differ compared to the other trials (52 vs. 53%), but DFS was significantly shorter (medians, 7.0 vs. 9.3 mos; p = 0.002), while OS did not differ (median, 8.4 mos), nor did survival following attainment of CR (13.9 vs. 14.5 mos; p = 0.13). DFS was shorter on 9720 for patients both 60-69 (n = 480; 6.9 vs. 9.3 mos; p = 0.02) and 70-79 (n = 294; 7.4 vs. 10.3 mos; p = 0.04) years; there were too few CR patients ≥ 80 years (n = 20) to allow a reliable conclusion. Conclusions: This historical comparison suggests that a single consolidation course results in significantly shorter DFS for de novo AML patients ≥ 60 years, but has no effect on OS nor survival following attainment of CR. The value of administering additional consolidation courses to prolong DFS without an effect on OS is debatable. Outcomes within cytogenetic and molecular subsets as well as quality of life measurements would be of interest. DFS and OS have remained short among older AML patients over the 25-year period covered by these studies; experimental approaches, including nonmyeloablative allogeneic hematopoietic cell transplantation in appropriate patients, are thus warranted. No significant financial relationships to disclose.