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
Authors: Devillier Raynier , Bertoli Sarah , Prebet Thomas , Recher Christian , Vey Norbert 
Published: October 2019

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.