Current patient care commonly focuses on SYMPTOMS1-3

Current care can manage symptoms, but myelofibrosis remains1,4

Today’s MF care focuses on:

  • Reducing splenomegaly
  • Improving constitutional symptoms

Management strategies:

  • Low- and intermediate-1 risk: Watch and wait; anemia-directed therapy; other symptom-directed therapy based on the clinical situation1
  • Intermediate-2 and high-risk: JAK inhibition; ASCT (for select patients)5
  • Current guidelines recommend ASCT only for eligible patients who are predicted to have poor survival based on prognostic risk scores (IPSS, DIPSS, and DIPSS Plus)6
    • In a retrospective study, 3% of MF patients received ASCT7*
    • Low- and intermediate-1-risk patients are not routinely offered ASCT6

Myelofibrosis response can oftentimes be suboptimal and short-lived4,8

Clinical trial experience

A circular icon visualizing the percentage of patients that ended JAK inhibition therapy within 3 years

Clinical trial experience

of patients ended JAK inhibition therapy within 3 years of treatment initiation due to intolerance, loss of response, or disease progression​4†

Real-world experience

A circular icon visualizing the number of patients from 2011 to 2012 that ended JAK inhibition therapy within the first year

Real-world experience

of patients from 2011 to 2012 ended JAK inhibition therapy within the first year​8‡

A calendar icon symbolizing timepoints of the median treatment duration for patients with recurrent symptoms

In a retrospective study, the median duration of treatment for those who discontinued JAK inhibitors due to recurrent symptoms or splenomegaly after experiencing an initial response was 21 months vs 5.2 months for those who failed to respond​4

Even when patients are on treatment, their disease can continue to progress1

What causes MF progression?9-12

An illustration of uncontrolled malignant proliferation that contributes to MF progression

Uncontrolled
malignant
proliferation due to overactive signaling​

An illustration of an increased aberrant megakaryocyte production that causes myelofibrosis progression

Increased
aberrant
megakaryocyte
production

An illustration of a blood cell visualizing inflammation and myofibroblast activation that causes myelofibrosis progression

Inflammation
and myofibroblast activation

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

Extensive bone
marrow fibrosis
and progressive bone marrow failure​

Uncontrolled
malignant
proliferation due to overactive signaling​

Increased
aberrant
megakaryocyte
production

Inflammation
and myofibroblast activation

Extensive bone
marrow fibrosis
and progressive bone marrow failure​

Progressive bone marrow fibrosis can lead to continued symptoms and is associated with poor outcomes13,14

  • Symptom persistence: Inflammatory cytokine production leads to constitutional symptoms10-13
  • Patient impact: BMF-related anemia at diagnosis has been associated with inferior quality of life and poor outcomes; it may also limit patient treatment eligibility13,15

Patients may continue to experience disease progression due to the complex mechanisms of this heterogeneous disease4,9

Looking Beyond the JAK/STAT Pathway

*Retrospective study conducted by a single institution.7
†In a 24-week, placebo-controlled trial, 54.1% of patients with MF did not see an improvement of 50% or more in total symptom score at 24 weeks, even if they experienced reduced symptom burden (N=309).16
‡Based on analyses of 2 large US claims databases, IMS Health® and MarketScan®.8

ASCT=allogeneic stem cell transplantation; BMF=bone marrow fibrosis; DIPSS=Dynamic International Prognostic Scoring System; IPSS=International Prognostic Scoring System; JAK=Janus kinase; JAK/STAT=Janus kinase signal transducer and activator of transcription; MF=myelofibrosis.

References:

  1. Harrison CN, Schaap N, Mesa RA. Management of myelofibrosis after ruxolitinib failure. Ann Hematol. 2020;99:1177-1191. doi:10.1007/s00277-020-04002-9
  2. Newberry KJ, Patel K, Masarova L, et al. Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. Blood. 2017;130(9):1125-1131. doi:10.1182/blood-2017-05-783225
  3. Ross DM, Babon JJ, Tvorogov D, Thomas D. Persistence of myelofibrosis treated with ruxolitinib: biology and clinical implications. Haematologica. 2021;106(5):1244-1253. doi:10.3324/haematol.2020.262691
  4. Kuykendall AT, Shah S, Talati C. Between a rux and a hard place: evaluating salvage treatment and outcomes in myelofibrosis after ruxolitinib discontinuation. Ann Hematol. 2018;97:435-441. doi:10.1007/s00277-017-3194-4
  5. Schieber M, Crispino JD, Stein B. Myelofibrosis in 2019: moving beyond JAK2 inhibition. Blood Cancer J. 2019;9(9):74. doi:10.1038/s41408-019-0236-2
  6. Devlin R, Gupta V. Myelofibrosis: to transplant or not to transplant? Hematology Am Soc Hematol Educ Program. 2016;2016(1):543-551. doi:10.1182/asheducation-2016.1.543
  7. 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.2011.11.00
  8. Fonseca E, Silver RT, Kazis LE, Iqbal SU, Rose M, Khan N. Ruxolitinib discontinuation in patients with myelofibrosis: an analysis from clinical practice. Blood. 2013;112(21):2833. doi:10.1182/blood.V122.21.2833.2833
  9. 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
  10. 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
  11. 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
  12. Agarwal A, Morrone K, Bartenstein M, et al. Bone marrow fibrosis in primary myelofibrosis: pathogenic mechanisms and the role of TGF-β. Stem Cell lnvestig. 2016;3:5. doi:10.3978/j.issn.2306-9759.2016.02.03
  13. 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
  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
  15. Naymagon L, Mascarenhas J. Myelofibrosis-related anemia: current and emerging therapeutic strategies. HemaSphere. 2017;1(1):e1. doi:10.1097/HS9.0000000000000001
  16. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799-807. doi:10.1056/NEJMoa1110557