615. Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Commercially Available Therapy, excluding Transplantation I

Paola Minetto, Anna Candoni, Fabio Guolo, et al.

Authors Conclusion from the Abstract: Despite the potential bias due to the retrospective nature of the analysis, our data indicate that intensive fludarabine-high dose cytarabine-based induction exerts a strong anti-leukemic efficacy in younger AML patients carrying NPM1 mutation irrespectively of FLT3 mutational status. Our data potentially question the role of BMT in first CR in this setting.

Keith W. Pratz, Panayiotis Panayiotidis, Christian Recher, et al.

Authors Conclusion from the Abstract: Results showed a longer TTD in PRO measures of global health status, VAS, fatigue, and PF for pts receiving VEN combinations vs AZA or LDAC monotherapy, with significantly longer TTD observed for all PRO measures from the unadjusted and adjusted analyses in Viale-C, and for PF and health VAS in Viale-A. These results suggest that VEN conveys meaningful benefit in terms of HRQoL. Limitations included the small sample size beyond early cycles in these studies; however, the early separation of the TTD curves with the initial larger sample size, suggests that these results are not due to chance variability and are statistically valid. Overall the improvements in PROs with VEN are consistent with previous efficacy reports. In summary, VEN appears to have a positive impact on the HRQoL of pts with AML who are ineligible for intensive chemotherapy, leading to a longer preservation of functioning and overall health status.

Danielle Hammond, Sanam Loghavi, Marina Konopleva, et al.

Authors Conclusion from the Abstract: While not targeted therapy per se, we confirm that the combination of HMA+VEN leads to an impressive CR/CRi rate with longstanding DOR in IDH1/IDH2 mutated AML, particularly in the frontline setting and in NPM1 co-mutated disease. Although accompanying MRD negativity by flow cytometry is frequent, almost half of pts retain an IDH mutation detectable by NGS, suggesting a role for combination therapy with IDH inhibitors. Additionally, we identify excellent outcomes in the relapsed setting, although the presence of a RAS-pathway or TP53 mutation may confer treatment resistance. The high within-patient salvage response rates when switching between HMA+VEN and IDHi-containing regimens warrant further investigation of combination vs. sequential therapy approaches.

Andrew H Wei, Glen A Kennedy, Kirk L Morris, et al.

Authors Conclusion from the Abstract: SOR did not improve EFS when combined with intensive chemotherapy in adults with newly diagnosed FLT3-ITD AML. Although not powered for significance, SOR showed a trend for improved OS among patients with higher FLT3-ITD AR or receiving HCT in CR1. Further exploration of more potent FLT3 inhibitors in the pre- and post-allograft setting are warranted for patients with newly diagnosed FLT3 mutant AML.

Xinxin Cao, Ming-hui Duan, Ai-lin Zhao, et al.

Authors Conclusion from the Abstract: We first found more than 25% of adult LCH patients carried BRAF deletion (BRAF N486_P490 or BRAFN486_P491delinsS), which was related with MS and liver involvement. Also, we demonstrated that liver and spleen involvement indicates a worse prognosis in adult LCH, age older than 30 years at diagnosis predicted favorable EFS and a cytarabine-based regimen should be considered as a first-line treatment for adult MS or SS-m LCH patients.

Lisa Eidenschink Brodersen, Chad A. Hudson, Todd A. Alonzo, et al.

Authors Conclusion from the Abstract: These data demonstrate that CD74 expression is associated with more favorable disease characteristics and survival. Patients receiving bortezomib that were CD74-positive showed a superior response to therapy compared to patients who did not express CD74, by both OS and EFS, suggesting that CD74-positive childhood AML patients stand to benefit from bortezomib therapy. Bortezomib may induce a mechanistic response in CD74-positive AMLs similar to that in bortezomib-treated B-cell neoplasms and/or multiple myeloma, where bortezomib has proven to be beneficial.