Induction Therapy For AML Patients With Daunorubicin Dose Of 60 Mg/m² and 90 Mg/m² Results In Similar Complete Response Rate, Relapse-Free and Overall Survival

Author:

Devillier Raynier1,Bertoli Sarah2,Prebet Thomas3,Recher Christian4,Vey Norbert5

Affiliation:

1. Institut Paoli-Calmettes, Marseille, France,

2. Hematology, CHU Purpan, Toulouse, France,

3. Hematology Department, Institut Paoli Calmettes, Marseille, France,

4. Hematology Department, Hopital Purpan, Toulouse, France,

5. Institut Paoli Calmettes, Marseille, France

Abstract

Abstract Since 2000, daunorubicin (DNR) 60 mg/m²/d for 3 days combined with cytarabine 200 mg/m²/d CIV over 7 days is the standard induction regimen used by the french GOELAMS group for younger patients treated for AML. Recently, use of high dose DNR (90 mg/m²/d for 3 days) results in higher complete remission (CR) rate and better survival as compared with DNR 45 mg/m²/d for 3 days (Lowenberg, NEJM, 2009, Fernandez, NEJM, 2009). To date, no prospective data are available comparing DNR 60 mg/m²/d and 90 mg/m²/d for induction therapy. In this retrospective study, we report the outcome of 402 consecutive patients treated with either intensified induction (DNR90) or standard DNR60 regimen. Selection criteria were age<=60 years; APL and CBF AML were excluded; induction course with either DNR 60 mg/m² (DNR60 or 90 mg/m² DNR90; day-15 bone marrow blast evaluation at day 15 and for CR. All patients were treated consecutively between Jan 2000 and Aug 2012 in 2 French centers, DNR dose allocation was based on treatment period (DNR90 since 2010). Treatment followed GOELAMS LAM-2001 protocol schedule (Lioure, Blood, 2012). Briefly, patients received second induction course if they presented with more than marrow 5% blast at day-15 examination. Once in CR, 2 to 3 high-dose cytarabine consolidation courses were planned. All patients with matched related or unrelated donor were scheduled for transplant after 2 consolidation courses. A total of 402 patients were analyzed (340 treated with DNR60 and 62 with DNR90 respectively). Median age was 49 years (range: 16-60), median WBC was 7.2 G/L (range: 0.1-430), 76 (19%) had secondary AML (therapy related AML or acute transformation of a myelodysplastic syndrome) and 108 (27%) had unfavorable cytogenetics. Patient and disease characteristics were well balanced between DNR90 versus DNR60 except for higher WBC for DNR90 group (median 6.6 vs. 17.6, p=0.021). At day-15 marrow evaluation, 135 DNR60 patients (40%) and 23 DNR90 patients (37%) had more than 5% marrow blast, (p=0.406). Second induction course was given in 122 (36%) and 22 (35%) DNR60 and DNR90 patients respectively (p=0.489). CR was achieved in 244 (72%) and 46 (74%) in DNR60 and DNR90 patients respectively (p=0.412) while 266 DNR60 patients (78%) and 54 DNR90 patients (87%) achieved at least CRi (p=0.073). Induction death rate was similar between the 2 groups (2% vs. 5%, p=0.148). Median FU was 72 vs. 21 months for DNR60 vs. DNR90 respectively (p<0.001). Two-years Overall survival (OS) probability was 52% and 60% in DNR60 and DNR90 group respectively (p=0.329) (Figure 1). In the 320 patients achieving at least CRi after induction therapy, 2-years relapse-free survival (RFS) probability was 48% and 53% in DNR60 and DNR90 groups respectively (p=0.714) (Figure 1). In multivariate analyses, secondary AML, unfavorable cytogenetics, day-15 bone marrow blast => 5%, and WBC => 100 G/L were associated with shorter OS while only unfavorable cytogenetic abnormalities and WBC => 100 G/L adversely influenced RFS. In conclusion, we found that induction therapy based on daunorubicin at the dose of 60 mg/m² or 90 mg/m² were comparable for CR rate, OS, and RFS. This suggests that DNR60 might be equivalent to DNR90 that has recently been established as a standard of induction chemo for AML. Prospective trials are needed to confirm these findings. Disclosures: Prebet: CELGENE: Honoraria.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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