616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel Immunotherapeutics, Checkpoint Inhibitors, and BiTEs


Conclusion cited from the abstract: To our knowledge, this is the first large randomized trial of AZA with or without ICP blockade in older unfit AML and HR-MDS pts reported to date. No clinically meaningful difference in efficacy was observed between treatments for either cohort. No new safety signals or potential overlapping risks were identified with the combination. While the hypomethylating activity of AZA on PD-L1 gene was confirmed, no treatment-mediated induction of PD-L1 surface expression was observed on myeloid blasts.




Conclusion cited from the abstract: The CR/CRi rates and OS with Aza+Nivo+Ipi are encouraging, with median OS of >10 months in R/R high-risk AML, and the study is enrolling. PSI on pretherapy BM CD4 T-cells from pts treated with Aza+Nivo almost completely segregated Rs vs NRs (p=0.0317). This suggests a very significant and hitherto underappreciated immune diversity in AML and a critical need for biomarker based trials (as we are doing with molecular therapies) with immunotherapies in AML.




Conclusion cited from the abstract: Pembrolizumab can be safely administered after HiDAC salvage in R/R AML. Severe iRAE’s were uncommon despite administration after cytotoxic chemotherapy. The addition of pembrolizumab to HiDAC led to an encouraging overall CR rate meeting the primary endpoint of the study. Immunogenomic biomarker analyses consisting of B cell receptor amplicon sequencing, RNA-seq of blasts and CD8+ T cells, CD8+ T cell receptor repertoire, whole exome sequencing and flow cytometry analyses are ongoing to determine predictors of response. These results warrant further investigation of IR blockade and other immunomodulatory therapeutic strategies after intensive cytotoxic chemotherapy in AML.




Conclusion cited from the abstract: AZA/Pembro combination is safe, feasible and well tolerated for both R/R and newly dx older AML pts. Clinical activity is particularly notable in newly dx older AML pts. IRAEs occur and can be managed with steroids and supportive care in the majority of pts. Biomarker-based correlative studies are ongoing to better define specific subset of patients that may benefit from this approach.




Conclusion cited from the abstract: 

Preliminary data of AMG 673 dosed up to 72 µg provide early evidence of the molecule’s acceptable safety profile, drug tolerability, and anti-leukemic activity. An association was observed between PK/PD relationships that were consistent with the biological activity of AMG 673. These preliminary results support further dose escalation of the AMG 673 HLE BiTE® molecule in patients with R/R AML.






Conclusion cited from the abstract: AMV564 is well-tolerated and demonstrates anti-leukemic activity through T-cell engagement.