Current management approaches to HR-MDS and AML do not focus on immune system dysfunction and leukemic stem cell and blast over-proliferation1-3

These limitations may contribute to the challenges facing patients with HR-MDS and AML, including poor prognosis and limited duration of response

Current management approaches focus on1,4:

  • Epigenetic changes (ie, DNA methylation)
  • Genomic alterations (ie, FLT3, IDH, and TP53)
  • Deregulation of apoptosis (ie, overexpression of BCL-2)

AML, acute myeloid leukemia; BCL-2, B-cell lymphoma 2; FLT3, fms like tyrosine kinase 3; HMA, hypomethylating agent; HR-MDS, higher-risk MDS; IDH, isocitrate dehydrogenase; TP53, tumor protein p53.

 

 

Patient outcomes with HMAs and BCL-2 inhibitors remain sub-optimal5,6

Median duration of response is short
Patients with HR-MDS are still at risk for transformation to AML and death

 

 

Immuno-therapeutic approaches in HR-MDS and AML have yet to deliver durable outcomes to patients

  • Therapies like PD1/PDL1 inhibitors have attempted to address the immune component of myeloid diseases, but they did not achieve the impact they brought to the treatment of solid tumor10
  • Other types of immuno-therapeutic approaches that focus on the key complexities of myeloid diseases, such as immuno-myeloid therapy, may help address current challenges

 

 

References: 1. Fenaux P, Mufti G, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223-232. 2. Hollenbach P, Nguyen A, Brady H, et al. A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS ONE. 2010;5(2):e9001. 3. Pollyea DA, Amaya M, Strati P, Konopleva MY. Venetoclax for AML: changing the treatment paradigm. Blood Advances. 2019;3(24):4326-4335. 4. Stanchina M, Soong D, Zheng-Lin B, Watts JM, Taylor J. Advances in acute myeloid leukemia: recently approved therapies and drugs in development. Cancers. 2020;12(3225). doi:10.3390/cancers12113225. 5. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. New Engl J Med. 2020;383(7):617-629. 6. Platzbecker U. Treatment of MDS. Blood. 2019;133(10):1096-1107. 7. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465. 8. Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126(3):291-299. 9. Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30(21):2670-2677. 10. Bewersdorf JP, Shallis R, Zeidan A. Immune checkpoint inhibition in myeloid malignancies: moving beyond the PD-1/PD-L1 and CTLA-4 pathways. Blood Reviews. 2021. doi:10.1016/j.blre.2020.100709.

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