A randomized, phase II study (NCT01349972), compared alvocidib, a CDK9 inhibitor, followed by cytarabine and mitoxantrone (FLAM) versus cytarabine and daunorubicin (7+3) in newly diagnosed patients with acute myeloid leukemia (AML) with non-favorable risk cytogenetics. The primary endpoint of the study was complete remission (CR).
Previously published data from this study demonstrated that despite significantly higher CR rates in patients in the FLAM arm, there was no difference in the overall survival (OS) and event-free survival (EFS) with a median follow-up of 811 days (1–1217 days) between both arms. The final results of this study with a longer follow-up were reported in a Letter to the Editor of Leukemia Research by Joshua F. Zeidner from The Johns Hopkins Hospital, Sidney Kimmel Comprehensive Cancer Center, Baltimore, US, and colleagues.
Between May 25, 2011 and July 26, 2014, 165 patients (median age = 59 years, range: 19–70) were enrolled and randomized 2:1 to receive either FLAM (n = 109) or 7+3 (n = 56). The final data lock was November 21, 2017.
- Median follow-up: 1,644 days (range, 1–2203 days)
- Overall, 70% (76/109) of patients in the FLAM arm and 70% (39/56) of patients in the 7+3 arm died
- Survival in the FLAM and 7 +3 arm respectively:
- 5-year OS rates: 28% (95% CI, 21–39%) vs 26% (95% CI, 16–43%), HR = 1.15 (0.78–1.69), P = 0.5
- 5-year event-free-survival: 19% (95% CI, 10%–35%) and 26% (95% CI,14%–48%), HR = 0.75 (0.5–1.14), P = 0.18
- OS in patients aged < 50 years: 56% (95% CI, 40–78%) vs 36% (95% CI, 18–72%)
In summary, the long-term follow-up of this phase II randomized study demonstrates that FLAM leads to higher CR rates compared to 7 + 3 induction in patients with newly diagnosed AML patients. However, there were no significant differences seen in OS or EFS between both arms.
The researchers concluded that despite the lack of improvement in OS for FLAM when compared with 7 + 3, these findings corroborate “alvocidib’s activity in AML and support further development.” Ongoing trials of alvocidib will provide further direction for its role in the current treatment armamentarium for AML.”