Background: Patients with core-binding factor acute myeloid leukemia (CBF-AML) have favourable outcomes when treated with standard anthracycline based induction and repeated cycles of cytarabine based consolidation. CBF-AML exhibit high rates of remission, overall survival, and relapse-free survival even without allogenic stem cell transplant (alloSCT). The exact number of consolidation cycles necessary for optimal outcomes, however is unknown. While early studies suggested that 3 or 4 cycles of high dose cytarabine (HiDAC) are associated with better outcomes relative to 1 cycle (Byrd, 1999 & Byrd, 2004), the effects of 2 cycles, has not been studied in this patient group. In this study, we evaluated the impact of 2 cycles of consolidative chemotherapy on the clinical outcomes of patients with CBF-AML.

Methods: Prior to 2012 patients with CBF-AML treated in Edmonton, Canada, were intended to receive 2 cycles of HiDAC after a complete remission (CR) following a single induction cycle ± intensification treatment (given if having >5% blasts on a day+14 marrow). Following a change in institutional policy, patients treated after 2012 were intended to receive 3 cycles of consolidation treatment. c-kit testing was not available prior to 2009 but thereafter all patients with c-kit mutations were offered alloSCT in first CR. In contrast, patients treated in Vancouver, Canada underwent similar induction but were intended to receive three consolidative cycles throughout the entire study period. Pooled data was retrospectively analyzed for all patients with CBF-AML treated in these two Canadian centres between 2003-2017 using an intention to treat approach.

Results: Overall, 108 patients were identified with a median age of 48 (range 17-75). Sixty-four patients (59%) were male. Seventy-four patients (68.5%) were intended for 3 cycles of consolidation therapy and 34 patients (31.5%) for 2 cycles. There were no differences in baseline characteristics of the analyzed patients (Table 1). There was also no significant difference in the number of patients who received intensification chemotherapy due to day +14 residual disease, the number of induction deaths, or CR rate at end of induction. Six patients intended to receive 2 cycles of consolidation were transplanted in CR1 compared with 5 who were intended to receive 3 cycles (p=0.09). Rates of hospitalization, median length of hospital stay, bacteremic events, intensive care requirements, and deaths during consolidation therapy did not differ significantly between the two groups.

Median follow-up time from CR was significantly longer in the 2 consolidation cycle group relative to the 3 consolidation cycle group (85 months vs. 30 months, p<0.0001). Of the 34 patients intended for 2 cycles of consolidation, there were 9 deaths and an additional 4 relapses, for a total event rate of 38.2%. Within the 74 patients intended to receive 3 cycles of consolidation there were 18 deaths and an additional 13 relapses for a total event rate of 41.9% (p=0.83)

There was no significant difference in overall survival (p=0.96; Figure 1, 5-year OS 73% for the 2 cycle consolidation group v 71% for the 3 cycle consolidation group), relapse-free survival when censored for transplant (p=0.61; Figure 2, 5-year RFS 63% for the 2 cycle consolidation group v 57% for the 3 cycle consolidation group, or event-free survival (p=0.88; 5-year EFS 54% for the 2 cycle consolidation group v 52% for the 3 cycle consolidation group) within the two groups. Multivariate analysis revealed that patients age, cytogenetics [t(8;21), inv(16)/t(16;16)], or transplantation in CR1 did not influence rates of overall survival or relapse-free survival between the two cohorts.

Conclusions: These data suggest that the use of 2 chemotherapy consolidation cycles compared with 3 does not diminish relapse-free survival or overall survival in patients with CBF-AML. Reduction in chemotherapy may provide both economic and quality of life benefits for patients. Larger prospective studies are necessary to confirm these findings.

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Disclosures

Hogge: Novartis, Roche, and Sanofi: Consultancy.

Topics:
chemotherapy regimen, cytogenetics, treatment outcome, consolidation therapy, cytarabine, transplantation, anthracycline antibiotics, bone marrow transplantation, allogeneic, complete remission, core-binding factor

Author notes

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Asterisk with author names denotes non-ASH members.

© 2017 by The American Society of Hematology
2017
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