615. Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Induction and Post-Remission Therapy
Conclusion cited from the abstract: In this randomized phase II study, DAC maintenance for 1 year after intensive AML therapy was associated with improved HR for OS and a trend for DFS, using protocol-specified statistical design. Furthermore there was a significant impact on OS for the FLT3-ITD-negative population. We acknowledge limitations based on incomplete accrual due to early termination of the parent E2906 study, and inherent to the phase 2 design of this E2906 endpoint, but results suggest an important impact of DAC maintenance on survival. These data strongly support a definitive phase III randomized study of DAC maintenance, particularly focused on the large intermediate risk FLT3-ITD-negative subgroup.
Conclusion cited from the abstract: To our knowledge, this is the largest population-based study to examine practice patterns and induction mortality for AML pts receiving “7+3” in the US. One of seven pts receiving 7+3 died in the hospital during induction or was discharged to hospice. We observed high use of intensive resources. IC-related mortality, use of any antifungal px, and use of mold-directed antifungal px were significantly better in high-volume hospitals compared to low- and medium-volume hospitals. Further analyses are ongoing to examine other predictors of IC-related deaths. Improved understanding of factors that predict induction-related mortality with 7+3 is vital to develop strategies that improve patient outcomes.
Conclusion cited from the abstract: With the limitation of a small trial, we conclude that post-remission Aza in elderly AML patients receiving standard induction-consolidation chemotherapy is safe and is well-tolerated. Noteworthy, in patients over 73 years of age, Aza significantly prolongs DFS up to 5 years.
Johann K. Hitzler, et al.
Conclusion cited from the abstract: MRD measured by multi-dimensional flow cytometry is insufficient to identify a subset of ML-DS patients for whom HD-AraC/E.coliasparaginase can be eliminated from treatment. Cytogenetic profiling may aid in further refining risk-based subsets of ML-DS patients. Additional approaches to risk stratification of ML-DS should be pursued, which take into account the emerging genetic events that co-operate with mutant GATA1 in the development of ML-DS. At this time, HD-AraC/E.coli asparaginase should be included in the treatment of ML-DS, regardless of MRD.
Katherine Tarlock, et al.
Conclusion cited from the abstract:
We show that sorafenib improved outcomes among the HAR ITD+/WT1+ patients, as this group of patients who did not receive sorafenib had very inferior outcomes, in line with previous findings for this poor risk cohort, while patients treated with sorafenib did much better with outcomes similar to other ITD+ patients. However, sorafenib failed to improve outcomes for NUP98-NSD1+ patients, further highlighting that novel therapeutic strategies will be needed for this group of patients. As the addition of FLT3-I is investigated in HAR FLT3/ITD+ patients, evaluation of its impact across patients with additional oncogenic mutations will be critical to determine which patients will derive the most benefit from this strategy.
Vijaya R. Bhatt, et al.
Conclusion cited from the abstract: Our model to personalize AML therapy selection represents an innovative approach to precision medicine that incorporates both geriatric assessment for patient profiling and genetic profiling of leukemia cells. Geriatric assessment demonstrated high frequency of impairment in objective physical and cognitive function. Patients were able to start therapy within a median of 2 days following enrollment. Pragmatic aspects of the trial included broad eligibility criteria and co-management of patients with community oncologists. Our pre-planned interim analysis data appear promising with lower rates of early mortality compared to unmatched historical controls.