Idarubicin Appears Equivalent to Dose-Intense daunorubicin for AML Induction

Abstract

AbstractAbstract ▪3581▪This icon denotes a clinically relevant abstractWorldwide 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-valueNumber2837Male13180.8592Age/median (range)56 (24–73)48 (21–72)0.1508Age >601060.0708Age>5514120.31Weight/kg (range)84.8 (51–124)82.8 (48–130)0.6831BSA1.92 (1.45–2.30)1.93 (1.47–2.43)0.9233Percent blasts prior to therapy63.8 (15–100)50.3 (20–95)0.0575Maximum WBC prior to therapy25.7 (0.2–137)35.3 (0–252)0.4365NPM positive (%)7/22 (32)6/25 (25)0.5499FLT-3 ITD (%)6/23 (26)4/32 (12.5)0.2902Karyotype (Cytogenetics)Good, %3/28 (11)8/35 (23)0.3187Intermediate8/28 (29)12/35 (34)0.7864Unfavorable17/28 (61)15/35 (43)0.2074Unknown0/28 (0)2/37 (5)0.5019Combined risk factors (Cyto+Molecular)Good, %3/28 (11)8/36 (22)0.3217Intermediate8/28 (29)9/36 (25)0.7818Unfavorable17/28 (61)19/36 (53)0.6149ResultsComplete remission (%)17/28 (61)15/37 (41)0.1072Karyotype (Cytogenetics)17/28 (61)13/35 (37)0.2937Good2/3 (67)5/8 (63)0.99Intermediate5/8 (63)5/12 (42)0.649Unfavorable10/17 (65)3/15 (20)0.0359Combined risk factors (Cyto+Molecular)17/28 (61)14/36 (39)0.1072Good2/3 (67)5/8 (63)0.99Intermediate5/8 (63)5/9 (56)0.99Unfavorable10/17 (65)4/19 (2)0.0388Age> 608/10 (80)1/6 (17)0.035Age <609/18 (50)14/31 (45)0.7746Age>557/14 (50)2/13 (15)0.0063CTC grade 3–4 toxicity (excluding cytopenias)7/27 (26)5/37 (14)0.3311Non-relapse mortality5/27 (19)2/37 (5)0.1222 Disclosures:No relevant conflicts of interest to declare.