Abstract

Abstract 3581

Worldwide cancer drug shortages have recently required the substitution of daunorubicin, the “gold standard” anthracycline for idarubicin for induction therapy in acute myeloid leukemia(AML). Previously published randomized trials have shown idarubicin (12/m2) to be equal to, or better than daunorubicin (45–50mg/m2) for achieving complete remission(Blood. 1991 Apr 15;77(8):1666–74). It is currently unknown whether these results can be extrapolated when compared to intensified doses of daunorubicin(90mg/m2), shown to improve the CR rate when compared to 45 mg/m2 (N Engl J Med. 2009 Sep 24;361(13):1249–59). We therefore conducted an observational study to compare CR rates in AML patients who received either daunorubicin 90mg/m2 or idarubicin 12mg/m2 for the treatment of newly diagnosed AML.

Methods:

Medical records were used to identify newly diagnosed patients with AML who received daunorubicin 90mg/m2(Dau-90) or idarubicin 12mg/m2(Ida-12) between 1/2007 and 6/2012. Patients with APL were excluded. MDS patients who evolved to AML were included. AML was diagnosed by WHO criteria. Patients received daunorubin 90mg/m2 IV bolus or idarubicin 12mg/m2 IV bolus on days 1–3. Cytarabine 100mg/m2 by continuous infusion was given concomitantly on day 1–7 to both groups. All patients underwent marrow biopsy on day 14 after initiation of therapy. If residual disease was found, patients were considered treatment failure. Patients without residual disease were re-biopsied around the time of WBC recovery to assess CR. CR rates are reported after a single induction course.

Results:

28 Ida-12 and 37 Dau-90 patients were identified. Table 1 shows patient demographics and outcomes. There was no significant baseline difference between the 2 study arms for gender, age, weight, maximum WBC prior to therapy, cytogenetic risk group, percent of patients with FLT-3 ITD or NPM mutations, or combined risk factors. A non-significant trend was observed in the percent of marrow blasts prior to therapy and in the number of patients>60years(but not for age >55) within the Ida-12 study arm. Overall CR was similar between the Ida-12 and Dau- 90 treatment groups(p<0.1072) Subset analysis shows CR rates were significantly higher in Ida-12 treated patients who had an unfavorable karyotype(p<0.0359) or unfavorable combined cytogenetic risk(0.0388) or for age > 55 years(p<.0063). Overall morbidity and mortality was similar between groups.

Conclusion:

Ida-12 appears to be as effective as Dau-90 for achieving CR after a single induction course. Thus, Thus, substitution of Ida-12 for Dau-90 during times of drug shortages appears acceptable. Ida-12 may potentially be superior for patients >55 years or for those with unfavorable cytogenetics. These results warrant validation from a randomized clinical trial.

CharacteristicIda12Dau-90p-value
Number 28 37  
Male 13 18 0.8592 
Age/median (range) 56 (24–73) 48 (21–72) 0.1508 
Age >60 10 0.0708 
Age>55 14 12 0.31 
Weight/kg (range) 84.8 (51–124) 82.8 (48–130) 0.6831 
BSA 1.92 (1.45–2.30) 1.93 (1.47–2.43) 0.9233 
Percent blasts prior to therapy 63.8 (15–100) 50.3 (20–95) 0.0575 
Maximum WBC prior to therapy 25.7 (0.2–137) 35.3 (0–252) 0.4365 
NPM positive (%) 7/22 (32) 6/25 (25) 0.5499 
FLT-3 ITD (%) 6/23 (26) 4/32 (12.5) 0.2902 
Karyotype (Cytogenetics)    
Good, % 3/28 (11) 8/35 (23) 0.3187 
Intermediate 8/28 (29) 12/35 (34) 0.7864 
Unfavorable 17/28 (61) 15/35 (43) 0.2074 
Unknown 0/28 (0) 2/37 (5) 0.5019 
Combined risk factors (Cyto+Molecular)    
Good, % 3/28 (11) 8/36 (22) 0.3217 
Intermediate 8/28 (29) 9/36 (25) 0.7818 
Unfavorable 17/28 (61) 19/36 (53) 0.6149 
Results    
Complete remission (%) 17/28 (61) 15/37 (41) 0.1072 
    Karyotype (Cytogenetics) 17/28 (61) 13/35 (37) 0.2937 
        Good 2/3 (67) 5/8 (63) 0.99 
        Intermediate 5/8 (63) 5/12 (42) 0.649 
        Unfavorable 10/17 (65) 3/15 (20) 0.0359 
    Combined risk factors (Cyto+Molecular) 17/28 (61) 14/36 (39) 0.1072 
        Good 2/3 (67) 5/8 (63) 0.99 
        Intermediate 5/8 (63) 5/9 (56) 0.99 
        Unfavorable 10/17 (65) 4/19 (2) 0.0388 
Age> 60 8/10 (80) 1/6 (17) 0.035 
Age <60 9/18 (50) 14/31 (45) 0.7746 
Age>55 7/14 (50) 2/13 (15) 0.0063 
CTC grade 3–4 toxicity (excluding cytopenias) 7/27 (26) 5/37 (14) 0.3311 
Non-relapse mortality 5/27 (19) 2/37 (5) 0.1222 
CharacteristicIda12Dau-90p-value
Number 28 37  
Male 13 18 0.8592 
Age/median (range) 56 (24–73) 48 (21–72) 0.1508 
Age >60 10 0.0708 
Age>55 14 12 0.31 
Weight/kg (range) 84.8 (51–124) 82.8 (48–130) 0.6831 
BSA 1.92 (1.45–2.30) 1.93 (1.47–2.43) 0.9233 
Percent blasts prior to therapy 63.8 (15–100) 50.3 (20–95) 0.0575 
Maximum WBC prior to therapy 25.7 (0.2–137) 35.3 (0–252) 0.4365 
NPM positive (%) 7/22 (32) 6/25 (25) 0.5499 
FLT-3 ITD (%) 6/23 (26) 4/32 (12.5) 0.2902 
Karyotype (Cytogenetics)    
Good, % 3/28 (11) 8/35 (23) 0.3187 
Intermediate 8/28 (29) 12/35 (34) 0.7864 
Unfavorable 17/28 (61) 15/35 (43) 0.2074 
Unknown 0/28 (0) 2/37 (5) 0.5019 
Combined risk factors (Cyto+Molecular)    
Good, % 3/28 (11) 8/36 (22) 0.3217 
Intermediate 8/28 (29) 9/36 (25) 0.7818 
Unfavorable 17/28 (61) 19/36 (53) 0.6149 
Results    
Complete remission (%) 17/28 (61) 15/37 (41) 0.1072 
    Karyotype (Cytogenetics) 17/28 (61) 13/35 (37) 0.2937 
        Good 2/3 (67) 5/8 (63) 0.99 
        Intermediate 5/8 (63) 5/12 (42) 0.649 
        Unfavorable 10/17 (65) 3/15 (20) 0.0359 
    Combined risk factors (Cyto+Molecular) 17/28 (61) 14/36 (39) 0.1072 
        Good 2/3 (67) 5/8 (63) 0.99 
        Intermediate 5/8 (63) 5/9 (56) 0.99 
        Unfavorable 10/17 (65) 4/19 (2) 0.0388 
Age> 60 8/10 (80) 1/6 (17) 0.035 
Age <60 9/18 (50) 14/31 (45) 0.7746 
Age>55 7/14 (50) 2/13 (15) 0.0063 
CTC grade 3–4 toxicity (excluding cytopenias) 7/27 (26) 5/37 (14) 0.3311 
Non-relapse mortality 5/27 (19) 2/37 (5) 0.1222 
Disclosures:

No relevant conflicts of interest to declare.

Author notes

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