Further exploration is needed to uncover solutions that are able to control BOTH THE SYMPTOMS AND THE UNDERLYING DISEASE1,2

Current and potential future goals for managing myelofibrosis could include1-6:

An illustrations of a spleen visualizing spleen volume reduction as a treatment management goal

Sustained reduction of spleen volume

An illustration visualizing improved symptom responses as a result of successful myelofibrosis management

Improved
symptom responses

A calendar icon visualizing anemia response for longer transfusion-free periods as a result of successful myelofibrosis management

ANEMIA RESPONSE
for longer transfusion-free periods

An illustration of a bone visualizing the reversal of bone marrow fibrosis as a result of successful myelofibrosis management

Reversal of
bone marrow fibrosis

An illustration visualizing reduced variant allele frequency burden as a result of successful myelofibrosis management

Reduced VARIANT ALLELE FREQUENCY (VAF)

An illustration visualizing improved overall survival as a result of successful myelofibrosis management

Improved
OVERALL SURVIVAL

In a US MPN Landmark survey, the most important treatment goal for patients with myelofibrosis was to slow or delay disease progression7

  • Other important goals for patients included better quality of life, healthy blood counts, and symptom improvement7

A closer look at some potential management goals:

Sustained reduction of spleen volume

JAK inhibition typically achieves SVR ≥35% in ≈40% of patients at 24 weeks8,9

The majority may not sustain SVR10

An illustration symbolizing the percentage of patients that don't sustain spleen volume reduction

≈70% did not sustain SVR at ≈3 years
(Landmark clinical trial)10

≈70% did not sustain SVR at
≈3 years (Landmark clinical trial)10

Anemia response for longer transfusion-free periods

All patients with MF are at risk of developing anemia3

At diagnosis, nearly 40% of patients with MF have hemoglobin (Hb) levels <10 g/dL and nearly one-quarter are already RBC transfusion dependent3

An illustrations of a blood drop visualizing durable anemia response as an outcome of successful treatment management

In some patients, durable anemia response could help mitigate symptoms or allow for longer transfusion-free periods, improving quality of life3,11

Reversal of bone marrow fibrosis

BMF is a key diagnostic feature (2008 WHO criteria) of MF12

In a long-term follow-up study, reduced BMF* with JAK inhibition was correlated with:

An illustrations of a spleen visualizing spleen volume reduction as a treatment management goal

Increased SVR13

An illustration symbolizing the management goal of decreased leukoerythroblastosis

Decreased leukoerythroblastosis13

Targeting the malignant stem cell may disrupt the downstream signaling that contributes to BMF2,5,14

Reduced variant allele frequency (VAF)15-18

VAF refers to the allelic burden in mutations such as JAK2 V617F that are present in myelofibrosis and other MPNs15,16,18

In some studies, reductions in VAF have been associated with clinical improvements, such as:

Reversal of BMF16,18

An illustrations of a spleen visualizing improved spleen response as an outcome of successful treatment management

Reduction in spleen volume17

The heterogeneity of treatment experiences, durations, and response definitions continues to pose clinical challenges19

Assessing myelofibrosis response

Definitions of optimal myelofibrosis response are variable and lack clinical consensus; however, some factors to consider may include19:

An illustration symbolizing the target reduction in spleen size, and persistence of constitutional symptoms during therapy

Target reduction in19:

  • Spleen size
  • Persistence of constitutional symptoms during therapy
An illustration of the time to (and degree of) clinical improvement

Time to (and degree of) clinical improvement19:

  • Monitoring response during the first 3 to 6 months of treatment may help inform the approach moving forward

Per IWG-MRT response criteria, benefit must last for ≥12 weeks to qualify as a response20

Rethink the ways we look at myelofibrosis and disease progression5,21,22

Sign up for important updates and information about MF

AbbVie is committed to ongoing research in myelofibrosis.

*Measured by grade of reticulin and collagen deposition.13

BMF=bone marrow fibrosis; IWG-MRT=International Working Group-Myeloproliferative Neoplasms Research and Treatment; JAK=Janus kinase; JAK/STAT=Janus kinase signal transducer and activator of transcription; MF=myelofibrosis; MPN=myeloproliferative neoplasm; RBC=red blood cells; SVR=spleen volume reduction; WHO=World Health Organization.

References:

  1. Pettit K, Odenike O. Novel therapies for myelofibrosis. Curr Hematol Malig Rep. 2017;12(6):611-624. doi:10.1007/s11899-017-0403-0
  2. 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
  3. Naymagon L, Mascarenhas J. Myelofibrosis-related anemia: current and emerging therapeutic strategies. HemaSphere. 2017;1(1):e1. doi:10.1097/HS9.0000000000000001
  4. Tefferi A, Guglielmelli P, Pardanani A, Vannucchi AM. Myelofibrosis treatment algorithm 2018. Blood Cancer J. 2018;8(8):72. doi:10.1038/s41408-018-0109-0
  5. 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
  6. 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
  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. 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
  9. Pardanani A, Harrison C, Cortes JE, et al. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis: a randomized clinical trial. JAMA Oncol. 2015;1(5):643-651. doi:10.1001/jamaoncol.2015.1590
  10. Verstovsek S, Mesa RA, Gotlib J, et al. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017;10(1):55. doi:10.1186/s13045-017-0417-z
  11. Mughal TI, Vaddi K, Sarlis NJ, Verstovsek S. Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes. Int J Gen Med. 2014;7:89-101. doi:10.2147/IJGM.S51800
  12. 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
  13. Kvasnicka HM, Thiele J, Bueso-Ramos CE. Long-term effects of ruxolitinib versus best available therapy on bone marrow fibrosis in patients with myelofibrosis. J Hematol. 2018;11(1):42. doi:10.1186/s13045-018-0585-5
  14. Santos FPS, Verstovsek S. Therapy with JAK2 inhibitors for myeloproliferative neoplasms. Hematol Oncol Clin North Am. 2012;26(5):1083-1099. doi:10.1016/j.hoc.2012.07.008
  15. Vannuchi AM, Pieri L, Guglielmelli P. JAK2 allele burden in the myeloproliferative neoplasms: effects on phenotype, prognosis and change with treatment. Ther Adv Hematol. 2011;2(1):21-32. doi:10.1177/2040620710394474
  16. Hasselbalch HC. The role of cytokines in the initiation and progression of myelofibrosis. Cytokine Growth Factor Rev. 2013;24(2):133-145. doi:10.1016/j.cytogfr.2013.01.004
  17. Pemmaraju N, Verstovsek S, Mesa R, et al. Defining disease modification in myelofibrosis in the era of targeted therapy. Cancer. 2022;128(13):2420-2432. doi:10.1002/cncr.34205
  18. Harrison CN, McLornan DP. Current treatment algorithm for the management of patients with myelofibrosis, JAK inhibitors, and beyond. Hematology Am Soc Hematol Educ Program. 2017;(1):489-497. doi:10.1182/asheducation-2017.1.489
  19. 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
  20. Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013;122(8):1395-1398. doi:10.1182/blood-2013-03-488098
  21. Rubert J, Qian Z, Andraos R, Guthy DA, Radimerski T. Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival. BMC Cancer. 2011;11:24. doi:10.1186/1471-2407-11-24
  22. Tremblay D, Mascarenhas J. Next generation therapeutics for the treatment of myelofibrosis. Cells. 2021;10(5):1034. doi:10.3390/cells10051034