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COULD RESEARCH INTO A NEW CLASS OF IMMUNOTHERAPY
ADVANCE OUR UNDERSTANDING OF HIGHER-RISK MDS?

Across certain tumor types, immunotherapy has helped transform treatment for patients with cancer1

A graphic showing B- and T-cell checkpoint inhibitors.
  • T-cell checkpoint inhibitors have paved the way in immunotherapy by working in the adaptive immune system to effectively treat a number of solid tumors1
  • However, immunotherapies targeting the adaptive immune system have only created meaningful outcomes in limited types of liquid tumors so far1
  • A new class of immunotherapy that looks beyond traditional immune checkpoint inhibitors is needed

Is there more of the immune system left to unlock?

A graphic showing a macrophage.
  • Because higher-risk MDS cells can overexpress “don’t eat me” signals as a macrophage defense mechanism, research into phagocytic signals may lead to important discoveries in the ongoing case against HR-MDS2
  • Could research into decreasing the antiphagocytic CD47 signals expressed by malignant cells lead us to clues about HR-MDS?

Therapeutic advancement in HR-MDS has been limited in the last 15 years, leaving patients and physicians ill-equipped for far too long3,4

A graphic with an IV bag.
  • Hematopoietic stem cell transplantation (HSCT) is the only potentially curative option for patients with HR-MDS, but advanced age at diagnosis and comorbidities prevent a majority of patients with HR-MDS from receiving HSCT4

A graphic with the letters H, M, A, s which stand for Hypomethylating agents.
  • Hypomethylating agents (HMAs) are the current standard of care, but they fall short of generating complete responses in a majority of higher-risk patients4,5
    • Response rates to HMAs are limited. In a randomized, open-label, phase III study, ~30% of patients with HR-MDS achieved either a complete response or partial response, and ~50% of patients with HR-MDS achieved hematologic improvement. The primary endpoint, median overall survival, was ~2 years6
    • Real-world data suggest that median overall survival with HMAs in HR-MDS is shorter than the best clinical trial overall survival outcomes reported, which is ~2 years6,7
  • A lack of durable responses with current HMAs for HR-MDS makes relapse, progression to AML, and high transfusion burden likely3,4,8

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AML, acute myeloid leukemia; MDS, myelodysplastic syndrome.

References:
  1. Salik B, Smyth MJ, Nakamura K. J Hematol Oncol. 2020;13(1):111. doi:10.1186/s13045-020-00947-6
  2. Swoboda DM, Sallman DA. Best Pract Res Clin Haematol. 2020;33(4):101221.
  3. Steensma DP. Blood Cancer J. 2018;8(5):47. doi:10.1038/s41408-018-0085-4
  4. Platzbecker U. Blood. 2019;133(10):1096-1107. doi:10.1182/blood-2018-10-844696
  5. Silverman LR, McKenzie DR, Peterson BL, et al. J Clin Oncol. 2006;24(24):3895-3903. doi:10.1200/JCO.2005.05.4346
  6. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Lancet Oncol. 2009;10(3):223-232. doi:10.1016/S1470-2045(09)70003-8
  7. Zeidan AM, Stahl M, Sekeres MA, et al. Cancer. 2017;123(19):3662-3672. doi:10.1002/cncr.30903
  8. Bell JA, Galaznik A, Blazer M, et al. Leuk Lymphoma. 2019;60(1):49-59. doi:10.1080/10428194.2018.1464155

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