MYELOFIBROSIS PROGRESSION is often incessant and not always apparent1,2

Understanding risk and features of MF

A circular icon visualizing the percentage of patients that will have intermediate-2 or high-risk disease at diagnosis

of patients will have intermediate-2 or high-risk disease at diagnosis3

A calendar icon visualizing the overall survival of intermediate-2 or high-risk patients

≈1.3 and ≈2.9 years median OS for high-risk and intermediate-2 MF, respectively4,5

Signs and symptoms of MF6,7

  • Myelofibrosis typically presents with splenomegaly, impaired blood cell production, and constitutional symptoms, including fatigue, night sweats, itching, fever, and weight loss

MF progression leads to extensive bone marrow fibrosis (BMF)—a key feature of the disease8

Potential consequences of BMF1,9,10

An illustration of a bone to visualize extensive bone marrow fibrosis that causes myelofibrosis progression

In some studies, extensive BMF was shown to contribute to impaired hematopoiesis and clinical features including, but not limited to, splenomegaly8-11

Higher-grade BMF has been shown to correlate with poor survival12,13

  • A retrospective study showed that patients with a higher-grade BMF had an ≈3-fold decrease in median survival vs patients with a BMF of ≤1 (P<0.001)12

In some studies, higher grades of BMF have been associated with clinical manifestations of myelofibrosis, including8,14:

An illustration of a blood drop to visualize the onset of anemia associated with higher grades of bone marrow fibrosis

Onset of
ANEMIA

An illustration of blood cells to visualize higher percentage of blasts associated with higher grades of bone marrow fibrosis

Higher percentage of
blasts in the peripheral blood

An illustrations of two spleens visualizing the increased spleen size associated with higher grades of bone marrow fibrosis

Increased
spleen size

A clipboard icon symbolizing the timepoints of higher risk assessment scores associated with higher grades of bone marrow fibrosis

Higher
Risk Assessment
Scores by IPSS/DIPSS

The consequences of myelofibrosis progression continue to impact patients’ lives1

Current Treatment Landscape

BMF=bone marrow fibrosis; DIPSS=Dynamic International Prognostic Scoring System; IPSS=International Prognostic Scoring System; JAK/STAT=Janus kinase signal transducer and activator of transcription; MF=myelofibrosis; OS=overall survival.

References:

  1. Kramann R, Schneider RK. The identification of fibrosis-driving myofibroblast precursors reveals new therapeutic avenues in myelofibrosis. Blood. 2018;131(19):2111-2119. doi:10.1182/blood-2018-02-834820
  2. Palandri F, Al-Ali HK, Guglielmelli P, et al. Impact of bone marrow fibrosis grade on response and outcomes in patients with primary myelofibrosis treated with ruxolitinib: a post-hoc analysis of the JUMP study. Poster EP1092 presented at: EHA2021; June 9-17, 2021; Virtual Congress.
  3. Tefferi A, Lasho TL, Jimma T, et al. One thousand patients with primary myelofibrosis: the Mayo Clinic experience. Mayo Clin Proc. 2012;87(1):25-33. doi:10.1016/j.mayocp.2011.11.001
  4. Pettit K, Odenike O. Novel therapies for myelofibrosis. Curr Hematol Malig Rep. 2017;12(6):611-624. doi:10.1007/s11899-017-0403-0
  5. Gangat N, Caramazza D, Vaidya R, et al. DIPSS Plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011;29(4):392-397. doi:10.1200/JCO.2010.32.2446
  6. Reilly JT, McMullin MF, Beer PA, et al. Guideline for the diagnosis and management of myelofibrosis. Br J Hematol. 2012;158(4):453-471. doi:10.1111/j.1365-2141.2012.09179
  7. Mesa RA, Miller CB, Thyne M, et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients’ overall health and productivity: the MPN Landmark survey. BMC Cancer. 2016;16:167. doi:10.1186/s12885-016-2208-2
  8. Zahr AA, Salama ME, Carreau N, et al. Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies. Haematologica. 2016;101(6):660-671. doi:10.3324/haematol.2015.141283
  9. Gleitz HFE, Kramann R, Schneider RK. Understanding deregulated cellular and molecular dynamics in the haematopoietic stem cell niche to develop novel therapeutics for bone marrow fibrosis. J Pathol. 2018;245(2):138-146. doi:0.1002/path.5078
  10. Agarwal A, Morrone K, Bartenstein M, Zhao ZJ, Verma A, Goel S. Bone marrow fibrosis in primary myelofibrosis: pathogenic mechanisms and the role of TGF-β. Stem Cell lnvestig. 2016;3(5):1-10. doi:10.3978/j.issn.2306-9759.2016.02.03
  11. Gleitz HFE, Pritchard JE, Kramann R, Schneider RK. Fibrosis driving myofibroblast precursors in MPN and new therapeutic pathways. HemaSphere. 2019;3(S2):142-145. doi:10.1097/HS9.0000000000000216
  12. Lekovic D, Gotic M, Perunicic-Jovanovic, et al. Contribution of comorbidities and grade of bone marrow fibrosis to the prognosis of survival in patients with primary myelofibrosis. Med Oncol. 2014;31(3):869. doi:10.1007/s12032-014-0869-8
  13. Gianelli U, Vener C, Bossi A, et al. The European Consensus on grading of bone marrow fibrosis allows a better prognostication of patients with primary myelofibrosis. Mod Pathol. 2012;25(9):1193-1202. doi:10.1038/modpathol.2012.87
  14. Nazha A, Estrov Z, Cortes J, Bueso-Ramos CE, Kantarjian H, Verstovsek S. Prognostic implications and clinical characteristics associated with bone marrow fibrosis in patients with myelofibrosis. Leuk Lymphoma. 2013;54(11):2537-2539. doi:10.3109/10428194.2013.769537