Dynamics of Molecular Response in Patients (pts) with Acute Myeloid Leukemia (AML) Withy Core Binding Factor (CBF) Abnormalities Treated with High-Dose Cytarabine Regimen
Authors: Jabbour Elias J. , Kantarjian Hagop M. , Cameron Yin , Ravandi Farhad , Cortes Jorge E. , Garcia-Manero Guillermo , Ghanem Hady , Kadia Tapan M. , Faderl Stefan , O'Brien Susan , Mathisen Michael S , Brandt Mark , Pemmaraju Naveen , Thomas Deborah A. , Bass Joyce , Borthakur Gautam 
Published: October 2019

Abstract 3609

Background:

AML associated with CBF abnormalities (CBF-AML) is the type of leukemia most responsive to cytarabine (ara-C) therapy and is of relative favorable prognosis. We have previously reported a complete remission (CR) rate of 93% (Borthakur et al. Cancer 2008).

Aim:

To investigate the molecular response to fludarabine, cytarabine, filgrastim, and GO (FLAG-GO) or idarubicin (FLAG-IDA) and the dynamic of this molecular response in newly diagnosed pts withCBF-AML.

Methods:

69 consecutive pts with newly diagnosed CBF-AML were assessed between 4/07 and 11/11. Of the 69 pts, 60 pts had regular monitoring testing and thus were eligible for this analysis. Quantitative reverse transcription PCR in peripheral blood/bone marrow samples was performed prior to therapy, at the documentation of the response and approximately every 3 months thereafter.

Results:

Median age was 48 yrs, range (19–78 yrs). 26 (43%) pts had inversion 16 and 34 (57%) t(8;21). 47 pts received FLAG-GO and 13 FLAG-IDA as induction/consolidation. The overall CR rate was 90% with median time to CR being 26 days, range 19–33 days. The CR rates for pts with inv 16 and t(8;21) were 88% and 91%, respectively. With a median follow-up of 32 months (range, 7 to 61), 51 pts remained alive; 6 (10%) pts relapsed with a median of 10.8 months (range, 7.8 to 20.5). The median overall and relapse-free survival was not reached. The 4-year OS and EFS rates were 79% and 77% respectively. All responders achieved a molecular response with the nadir being observed at a median of 7 months (range, 1 to 28) from the start of the therapy. 55 pts (92%) achieved a transcript level below 0.01% after a median of 4 months (range, 1 to 13) and 43 pts (72%) achieved a complete molecular response (CMR) or undetected level by PCR within 7 months (range, 1 to 28). Relapses were seen in 3/42 (7%) pts with CMR, 2/12 (17%) of pts with transcript level ≤0.01 and 1/5 (20%) of pts with transcript level >0.01 respectively (Fig. 1). The 4-year EFS and OS for pts achieving a CMR or not were 84% and 56% (p=0.015) and 88% and 51% (p=0.002), respectively. Figure 1 summarizes pt disposition. Of the 5 pts who never achieved a transcript level below 0.01%, one patient relapsed 5 months after achieving his nadir transcript value of6.08% and all remaining four pts have remained in CR for a median of 206 months (range, 7+ to 50+) despite persistent molecular disease. Of the 55 pts with a transcript level below 0.01%, 5 (9%) relapsed and 7 additional (13%, 3 of them with CMR) lost their molecular response to a level below 0.15% with no morphological relapse; 2 of the 3 with CMR regained a CMR after a median 15 months (range, 7 to 23 months).

Conclusion:

Front-line therapy of CBF-AML with FLAG-GO/IDA is highly efficacious and induces molecular responses in a significant number of pts. The achievement of CMR is associated with improvement of EFS and OS. Persistence of minimal disease and minor fluctuations in the transcript levels below 0.15% should be monitored and are not predictive of relapse.

Disclosures:

Ravandi: Genzyme/Sanofi: Honoraria. Faderl:Genzyme: Advisory Board Other, Research Funding.