Patients with HR-MDS and AML face a poor prognosis


About HR-MDS and AML

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) occur when hematopoietic stem cells, or progenitor cells, transform into leukemic stem cells, which then spread throughout the bone marrow.1,2

Patients with high-risk MDS (HR-MDS) and AML are generally older and immunocompromised, which may lead to tumor immune escape.3-5

These patients have T cells that:

an image showing exhausted t-cell

Are exhausted6

an image showing no proliferation

Do not proliferate7

an image showing no secretion of cytokines

Do not secrete cytokines6

an image showing the inability to kill malignant cells

Cannot kill malignant cells8

Patients with HR-MDS are at risk of developing AML

One-quarter of patients with HR-MDS will develop AML after a median duration of 8.7 months-1.6 years4

Epigenetic changes (ie, DNA methylation) and genomic alterations (ie, FLT3, IDH, and TP53) have been identified to be important to the pathophysiology of HR-MDS and AML.9,10

Prognosis remains unfavorable4,11-13

HR-MDS Median Overall Survival ≤ 1.6 years; UNFIT AML Median Overall Survival <1 year

Why a need remains for additional management approaches

TIM-3, T cell immunoglobulin and mucin domain-3.


References: 1. Warlick ED, Smith BD. Myelodysplastic syndromes: review of pathophysiology and current novel treatment approaches. Curr Cancer Drug Targets. 2007;7(6):541-558. 2. Lane SW, Gilliland DG. Leukemia stem cells. Semin Cancer Biol. 2010;20(2):71-76. 3. National Cancer Institute. SEER Cancer Statistics Review (CSR) 1975-2016. Accessed April 27, 2020. 4. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465. 5. Klepin HD. Myelodysplastic syndromes and acute myeloid leukemia in the elderly. Clin Geriatr Med. 2016;32(1):155-173. 6. Zhou Q, Munger ME, Veenstra RG, et al. Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood. 2011;117(17):4501-4510. 7. Sakuishi K, Ngiow SF, Sullivan JM, et al. TIM3+ FOXP3+ regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer. Oncoimmunology. 2013;2(4):e23849. 8. Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood. 2009;114(8):1545-1552. 9. Dinardo CD, Perl A. Advances in patient care through increasingly individualized therapy. Nat Rev Clin Oncol. 2019;16(2):73-74. 10. Platzbecker U. Treatment of MDS. Blood. 2019;133(10):1096-1107. 11. 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. 12. 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. 13. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.

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