Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Clinical Trials of Novel Drugs and Combinations in AML
Guillermo Garcia-Manero, Megan Othus, John M. Pagel, Jerald P. Radich, et al.
Conclusion: Treatment with IA is not more effective than 7+3 in younger pts with AML. Outcomes with IA or IA plus vorinostat are similar. In pts with favorable cytogenetics, outcomes were inferior with IA or IA+V when compared to 7+3, perhaps related to use of lower doses of ara-C during consolidation.
Bruno C. Medeiros, Jeffrey E. Lancet, Jorge E. Cortes, Laura F Newell, et al.
Conclusions: This subgroup analysis of patients aged 60–69 and 70–75 years with untreated secondary AML demonstrated that CPX-351 treatment had substantially greater median OS and higher CR+CRi rates than standard 7+3 (cytarabine and daunorubicin) in both age groups. In addition, somewhat more patients in each age group in the CPX-351 arm received allogeneic HCT compared with the 7+3 arm, with the greatest difference in the older age group. Future studies with larger patient groups are warranted.
Farhad Ravandi, Ellen K. Ritchie, Hamid Sayar, Jeffrey E. Lancet, et al.
Conclusions: After a median of 39.9 months of follow-up in the VALOR trial, the OS observed in patients ≥ 60 years of age treated with vosaroxin/cytarabine remains significantly improved versus placebo/cytarabine, with a separation of the survival curves through 48 months. The OS benefit is consistent among all older patients, even those ≥ 75 years of age, and is seen in patients with and without post-treatment transplantation. The updated survival data from VALOR continue to support the use of vosaroxin/cytarabine as a treatment option in patients ≥ 60 years of age with R/R AML.
Naval Daver, Hagop M. Kantarjian, Gail J. Roboz, Patricia L. Kropf, et al.
Conclusions: Guadecitabine showed good clinically activity in terms of CRc with acceptable safety profile in r/r AML patients with various standard poor prognostic factors. CRc with guadecitabine was associated with longer survival. While CRc was observed in all subgroups, patients with poor PS; poor risk cytogenetics; or with short time from last therapy had significantly worse survival. A randomized phase 3 study is being initiated with guadecitabine using the 10-day initial intensification regimen vs Treatment Choice in r/r AML patients.
Guillermo Garcia-Manero, Michael R. Savona, Steven D. Gore, Bart L. Scott, et al.
Conclusions: Among pts who were relapsed or refractory to prior HMA Tx, 35% had a hematologic response to CC-486, suggesting that prior HMA failure does not preclude future response to CC-486. Notably, the majority of pts had received >4 prior HMA Tx cycles; thus, prior failures to injectable HMAs were not likely due to inadequate duration of Tx. The ORR with CC-486 in pts who had received ≥6 cycles of the prior injectable HMA was the same as the ORR with CC-486 in all pts. Hypomethylating effects of HMAs are transient; unlike injectable HMAs, oral CC-486 can be administered over extended dosing periods (>7d) of the Tx cycle to produce sustained hypomethylating activity. There was no statistical difference in ORR between CC-486 7d and extended dosing in this small pt group. Nevertheless, given the short half-life and S-phase-restricted DNA incorporation of AZA (Li, Cancer Res, 1970), extending AZA exposure to >7d/cycle with CC-486 could increase the opportunity for cycling cells to incorporate AZA and expose more malignant progenitor cells to AZA, which may optimize therapeutic effects. Extended hypomethylation due to longer exposure to CC-486 may induce pts to respond to CC-486 who had failed prior injectable HMA Tx.
Jeffrey E. Lancet, Antje Hoering, Geoffrey L. Uy, Jorge E. Cortes, et al.
Conclusions: An exploratory analysis from this phase III study demonstrated that CPX-351, compared with standard cytarabine and daunorubicin, resulted in better outcomes after allogeneic HCT in older patients with high-risk AML, including 53% fewer deaths within 100 days of transplant. These results suggest that CPX-351 may provide an effective bridge to successful transplant for a very poor-risk subgroup of AML patients.