High Dose Cytarabine (HiDAC) and Mitoxantrone (MITO) Is An Effective Induction Therapy for High-Risk Acute Myeloid Leukemia (AML).
Authors: Larson Sarah , Campbell Nicholas , Huo Dezheng , Artz Andrew , Zhang Yanming , Gajria Devika , Green Margaret , Rahimova Gamar , Weiner Howard , Torres Monica , Odenike Olatoyosi , Godley Lucy A , Rich Elizabeth Shima , Thirman Michael , Larson Richard A. , Stock Wendy 
Published: October 2019

Abstract
Abstract 1048
Poster Board I-70

Background:
Patients with high risk AML, including those with advanced age, relapsed or refractory disease, unfavorable cytogenetics, therapy-related myeloid neoplasm (t-MN), and multiple medical co-morbidities, carry a poor prognosis and outcomes after 7+3 induction chemotherapy are poor. Complete remission (CR) rates tend to be low and range from 12-63% and induction death rates range from 10-26%. We developed a novel, timed-sequential regimen that takes advantage of synergy when MITO follows cytarabine (VW Quinones et al. ASH 1996. abstr 849).

Methods:
We performed a retrospective analysis of all AML patients, except those with t(15;17), who received HiDAC/MITO from 2001-2008 at our institution. Patients with high risk AML defined by age >60 and/or at least two adverse prognostic features (cytogenetics, co-morbid conditions, antecedent hematologic disorder) received cytarabine at 3gm/m2 over four hours (with dose reduction to 2gm/m2 for patients >60 years old) on days 1 and 5 plus mitoxantrone at 30mg/m2 (with dose reduction to 20mg/m2 for patients >60) over one hour immediately following the HiDAC on days 1 and 5. The primary endpoints of the study were CR and toxicity determined by induction death defined as death within 30 days of initiation of treatment.

Results:
78 consecutive patients received HiDAC/MITO for remission induction. The median age was 63 years (range 23-85); 27% of these patients had a Charlson comorbidity index (CCI) >2. The distribution of diagnoses is shown in the Table. 43 (56%) patients had poor-risk cytogenetics, 28 (37%) had intermediate-risk cytogenetics and 5 (7%) had good-risk cytogenetics. Overall CR rate was 45%, CRi rate 10%, refractory rate 36%, and induction death rate of 9%. Patients with AML with myelodysplasia related changes tended to have a lower CR rate (p=0.07) and were more likely to have a CRi. Notably, t-MN and relapsed/refractory patients had CR and induction death rates equivalent to de novo AML patients. Cytogenetics and CCI were also not associated with best response, p=0.7 and 0.94, respectively. Forty percent of patients proceeded to allogeneic stem cell transplantation (alloSCT) after receiving HiDAC/MITO. Overall survival at one year was 39%.

Conclusions:
In this high risk AML population, HiDAC/MITO induction was well tolerated and demonstrated an overall response rate of 55% and low induction death rate of 9%, allowing a substantial number of patients to proceed to alloSCT. High risk cytogenetics and multiple medical co-morbidities did not affect CR rate, and the CR rate was similar among relapsed/refractory, t-MN and de novo AML patients, which highlights the utility of this regimen for both high risk newly diagnosed and relapsed/refractory patients with AML.

Disclosures:
No relevant conflicts of interest to declare.