- |||||||||| Vyxeos (cytarabine/daunorubicin liposomal formulation) / Jazz
Review, Journal, IO Biomarker: Advances in Acute Myeloid Leukemia: Recently Approved Therapies and Drugs in Development. (Pubmed Central) - Nov 5, 2020 Antibody drug conjugates have resurfaced in the AML landscape and there have been numerous advances utilizing immunotherapies including immune checkpoint inhibitors, antibody-drug conjugates, bispecific T cell engager antibodies, chimeric antigen receptor (CAR)-T therapy and the development of AML vaccines. While there are dozens of ongoing studies and new drugs in the pipeline, this paper serves as a review of the advances achieved in the treatment of AML in the last several years and the most promising future avenues of advancement.
- |||||||||| [VIRTUAL] Universal Sensitive, Accurate and Precise Microchimerism Surveillance Solution for Allogeneic Hematopoietic Cell Transplant (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4180;
In summary, we have developed a sensitive, accurate and precise method for the universal detection and quantification of chimerism and potential early disease recurrence detection for allogeneic HCT patient surveillance. Because the method provides high sensitivity and consistent results for microchimerism detection, it may be particularly suited to help identify recurrence of primary disease in hematologic cancer patients with or without known cancer-associated genetic determinants.
- |||||||||| [VIRTUAL] Single and Dual Targeting Chimeric Antigen Receptor T-Cell Therapy in Acute Myeloid Leukemia (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4170;
In summary, we illustrate in-vitro data establishing the importance of scFv on CAR T cell cytotoxicity and exemplify for the first time an improved specificity of CARTs by targeting two antigens simultaneously in AML. Future work will involve examining the in-vivo dynamics of CAR CD123 and CAR CD123 CD33 on the hematopoietic system and on disease pathogenesis with an aim to proceed to phase I clinical trial.
- |||||||||| [VIRTUAL] Combinatorial Antigen Targeting Strategy for Acute Myeloid Leukemia (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4167;
P1 The events that lead to increased pCD3ʓ after antigen engagement in the dual transduced cells may in part be due to an overall increase in CAR expression but may also reflect superior CAR recruitment after antigen engagement. We are now comparing the formation, structure, and stability of immune synapses in single and dual targeting CARs for AML.
- |||||||||| [VIRTUAL] Nanobody Based Tri-Specific Chimeric Antigen Receptor to Treat Acute Myeloid Leukaemia (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4059;
Collectively, our data demonstrate that TanCAR T-cells operate as an OR gate mediating potent reactivity against target cell lines expressing single AML antigens in vitro. We now aim to test for optimal TanCAR formats and potential additive or synergistic responses where TanCAR T cells are co-cultured with AML cell lines in-vivo (Molm14, PDX).
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
[VIRTUAL] Correlating Clinical and Genomic Features with Ex Vivo Drug Sensitivity in Patients with Myelodysplastic Syndromes and Related Myeloid Neoplasms (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_3915; Cluster 1 (N=13) demonstrated the greatest ex vivo sensitivity to HMAs, HMA/venetoclax combinations, cytotoxic agents, kinase inhibitors, mTOR inhibitors, HDAC inhibitors, and PARP inhibitors, while cluster 3 (N=19) demonstrated the greatest ex vivo resistance (p<0.0001 for all comparisons)...A larger sample size is needed to evaluate combinations of mutations and better define associations between genotype and drug sensitivity phenotype. Ultimately, combining both genomics and functional screening may further refine personalized therapy selection for patients with MDS and related myeloid neoplasms.
- |||||||||| AMV-564 / J&J, Affimed
[VIRTUAL] Selectivity of T Cell Engager AMV564 Against Different Leukemic Blast Populations and Potential Application for Patient Selection (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2439; Furthermore, significant differences in potency across AML blasts were observed, which could be further impacted by the available T cells. While AMV564 has demonstrated anti-leukemic activity across an unselected relapsed/refractory AML population, this novel assay could be used to select patients in whom blasts are expressing CD33 in a predominantly clustered configuration, and thus identify patients most likely to experience deeper and more durable responses with AMV564 monotherapy.
- |||||||||| Xospata (gilteritinib) / Astellas
[VIRTUAL] Evolution of Gilteritinib Resistance from Residual Disease to Relapse (Channel 14 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_1602; Primary patient samples also demonstrated robust sensitivity to AURKB inhibitors only after gilteritinib exposure. Our results suggest that developing drug combinations that selectively target early resistance can improve the depth of initial response and may block development of later resistance mutations, thus improving the durability of response to gilteritinib.
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