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:
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
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. https://seer.cancer.gov/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.