Two Versus Three Cycles of Consolidation Therapy for Patients With AML

Patients with core-binding factor acute myeloid leukemia (CBF-AML) who received only two cycles of consolidation chemotherapy experienced similar rates of relapse-free survival (RFS) and overall survival (OS) as patients who received three cycles. These results raise questions about the value of adding a third cycle of consolidation therapy in this patient population.

“Patients with CBF-AML exhibit high rates of remission, OS, and RFS even without allogenic hematopoietic cell transplantation (alloHCT),” lead author Daniel Sawler, MD, BSc, of the University of Alberta in Edmonton, Canada, said during his presentation at the 2017 ASH Annual Meeting. “While early studies suggest that three or four cycles of high-dose cytarabine are associated with better outcomes than one cycle, the exact number of consolidation cycles necessary for optimal outcomes is unknown.”

In this retrospective analysis, the investigators compared survival and safety outcomes between patients who received two or three cycles of consolidative chemotherapy at two Canadian centers (in Edmonton and Vancouver) from 2003 to 2017. Prior to 2012, it was standard for patients with CBF-AML treated in Edmonton to receive two cycles of high-dose cytarabine after achieving a complete remission (CR) with a single induction cycle. After a change in institutional policy in 2012, patients received up to three cycles of consolidation treatment. Patients treated in Vancouver underwent similar induction therapy but received up to three consolidative cycles throughout the entire study period.

The pooled data from these two centers comprised 108 patients (median age= 48 years; range = 17-75 years), including:

  • 74 patients (68.5%) in the three-cycle cohort (median age = 43 years; range = 19-71 years)
  • 34 patients (31.5%) in the two-cycle cohort (median age = 49 years; range = 17-75 years)

Six patients in the two-cycle cohort and five patients in the three-cycle cohort received alloHCT during CR1 (p=0.09). The two groups did not differ in rates of hospitalization, median length of hospital stay, bacteremia events, intensive care requirements, and deaths during consolidation therapy.

Median follow-up from CR was significantly longer in the two-cycle cohort than the three-cycle cohort (85 vs. 30 months; p<0.0001). Among the patients who received two cycles of consolidation, nine died and four relapsed, for a total event rate of 38.2 percent. Among those who received three cycles of consolidation, 18 died and 13 relapsed, for a total event rate of 41.9 percent (p=0.83).

At five years, survival outcomes did not significantly differ between the two- and three-cycle cohorts:

  • 5-year OS: 73% vs. 71%, respectively (p=0.96)
  • 5-year RFS: 63% vs. 57% (p=0.61)
  • 5-year event-free survival: 54% vs. 52% (p=0.88)

“There was no appreciable difference in overall rate of consolidation complications,” the authors reported, with similar numbers of patients in both cohorts receiving chemotherapy intensification due to residual disease. Multivariate analyses also showed that age, cytogenetics, and proceeding to transplantation in CR1 did not influence rates of OS or RFS between the two groups.

“These data suggest that the use of two chemotherapy consolidation cycles, compared with three, does not diminish [survival] in patients with CBF-AML,” the authors concluded. “Reduction in chemotherapy may provide both economic and quality-of-life benefits for patients.”

The study’s findings are limited by its retrospective design, differential follow-up, and that it does not comment on the value of receiving four cycles of consolidation. A larger, randomized, prospective study comparing two cycles of consolidation chemotherapy with three or more is needed.

The authors report financial relationships with Novartis, Roche, and Sanofi.


Reference

Sawler D, Sanford D, Brandwein JM, et al. Two cycles of consolidation chemotherapy are associated with similar clinical outcomes to three cycles in AML patients with favorable risk cytogenetics. Abstract #464. Presented at the 2017 American Society of Hematology Annual Meeting, December 10, 2017; Atlanta, GA.

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