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Perspective

Anemia-related response end points in myelofibrosis clinical trials: current trends and need for renewed consensus

, , , ORCID Icon, &
Pages 703-715 | Received 22 Nov 2023, Accepted 18 Jan 2024, Published online: 06 Feb 2024

References

  • Arber DA , OraziA , HasserjianRPet al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood140(11), 1200–1228 (2022).
  • Tefferi A . Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. Am. J. Hematol.98(5), 801–821 (2023).
  • Vannucchi AM , BarbuiT , CervantesFet al. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol.26(Suppl. 5), v85–99 (2015).
  • Verstovsek S , MesaRA , GotlibJet al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N. Engl. J. Med.366(9), 799–807 (2012).
  • Pardanani A , HarrisonC , CortesJEet al. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis: a randomized clinical trial. JAMA Oncol.1(5), 643–651 (2015).
  • Harrison CN , SchaapN , VannucchiAMet al. Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study. Lancet Haematol.4(7), e317–e324 (2017).
  • Harrison C , KiladjianJJ , Al-AliHKet al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N. Engl. J. Med.366(9), 787–798 (2012).
  • Verstovsek S , GotlibJ , GuptaVet al. Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes. Onco. Targets Ther.7, 13–21 (2013).
  • Tefferi A , LashoTL , JimmaTet al. One thousand patients with primary myelofibrosis: the Mayo Clinic experience. Mayo Clin. Proc.87(1), 25–33 (2012).
  • World Health Organization . Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. https://apps.who.int/iris/bitstream/handle/10665/85839/WHO_NMH_NHD_MNM_11.1_eng.pdf (Accessed 24October2023).
  • Nicolosi M , MudireddyM , LashoTLet al. Sex and degree of severity influence the prognostic impact of anemia in primary myelofibrosis: analysis based on 1109 consecutive patients. Leukemia.32(5), 1254–1258 (2018).
  • Tefferi A , HudgensS , MesaRet al. Use of the Functional Assessment of Cancer Therapy–anemia in persons with myeloproliferative neoplasm-associated myelofibrosis and anemia. Clin. Ther.36(4), 560–566 (2014).
  • Cervantes F , DupriezB , PereiraAet al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood113(13), 2895–2901 (2009).
  • Gangat N , CaramazzaD , VaidyaRet 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.29(4), 392–397 (2011).
  • Passamonti F , CervantesF , VannucchiAMet al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood115(9), 1703–1708 (2010).
  • Naymagon L , MascarenhasJ. Myelofibrosis-related anemia: current and emerging therapeutic strategies. Hemasphere.1(1), e1 (2017).
  • Gerds AT , HarrisonC , ThompsonSet al. The burden of illness and the incremental burden of transfusion dependence in myelofibrosis in the United States. Presented at: 64th ASH Annual Meeting & Exposition. New Orleans, LA, USA, 10–13 December 2022 ( Poster 1729).
  • Pardanani A , LabordeRR , LashoTLet al. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia.27(6), 1322–1327 (2013).
  • Asshoff M , PetzerV , WarrMRet al. Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents. Blood129(13), 1823–1830 (2017).
  • Oh ST , TalpazM , GerdsATet al. ACVR1/JAK1/JAK2 inhibitor momelotinib reverses transfusion dependency and suppresses hepcidin in myelofibrosis phase 2 trial. Blood Adv.4(18), 4282–4291 (2020).
  • Chifotides HT , BoseP , VerstovsekS. Momelotinib: an emerging treatment for myelofibrosis patients with anemia. J. Hematol. Oncol.15(1), 7 (2022).
  • Verstovsek S , GerdsAT , VannucchiAMet al. Momelotinib versus danazol in symptomatic patients with anemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet401(10373), 269–280 (2023).
  • Mesa RA , KiladjianJJ , CatalanoJVet al. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in Janus kinase inhibitor-naive patients with myelofibrosis. J. Clin. Oncol.35(34), 3844–3850 (2017).
  • Harrison CN , VannucchiAM , PlatzbeckerUet al. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol.5(2), e73–e81 (2018).
  • GSK . Press release. www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia/ (Accessed 24October2023).
  • Ojjaara [momelotinib] . Prescribing information. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Ojjaara/pdf/OJJAARA-PI-PIL.PDF (Accessed 24October2023).
  • Oh ST , MesaR , HarrisonCet al. Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis. Blood Adv.7(19), 5835–5842 (2023).
  • Mohan SR , OhST , AliHet al. A phase 1/2 study of INCB000928 as monotherapy or combined with ruxolitinib (RUX) in patients (pts) with anemia due to myelofibrosis (MF). Presented at: 64th ASH Annual Meeting & Exposition.New Orleans, LA, USA, 10–13 December 2022 ( Poster 1714).
  • Gerds AT , VannucchiAM , PassamontiFet al. A phase 2 study of luspatercept in patients with myelofibrosis-associated anemia. Presented at: 61st ASH Annual Meeting & Exposition.Orlando, FL, USA, 7–10 December 2019 ( Oral presentation 557).
  • Gerds A , VannucchiAM , PassamontiFet al. Duration of response to luspatercept in patients (pts) requiring red blood cell (RBC) transfusions with myelofibrosis (MF) – updated data from the phase 2 ACE-536-MF-001 study. Presented at: 62nd ASH Annual Meeting & Exposition.Virtual, 5–8 December 2020 ( Oral presentation 2992).
  • Mesa R , HarrisonC , KiladjianJet al. INDEPENDENCE: a Phase III study of efficacy and safety of luspatercept versus placebo in patients with myeloproliferative neoplasm-associated myelofibrosis on JAK2 inhibitor therapy and requiring red blood cell transfusions. Presented at: 63rd ASH Annual Meeting & Exposition.Atlanta, GA, USA, 11–14 December 2021 ( Poster 1490).
  • ClinicalTrials.gov . www.clinicaltrials.gov/ct2/show/NCT04472598 (Accessed 24October2023).
  • ClinicalTrials.gov . www.clinicaltrials.gov/ct2/show/NCT04468984 (Accessed 24October2023).
  • Harrison C , KremyanskayaM , BosePet al. Pelabresib (CPI-0610) as add-on to ruxolitinib in myelofibrosis: durability of response and safety beyond week 24 in the phase 2 MANIFEST study. Presented at: 64th ASH Annual Meeting & Exposition.New Orleans, LA, USA, 10–13 December 2022 ( Poster 4344).
  • Rampal R , GrosickiS , ChraniukDet al. Pelabresib in combination with ruxolitinib for Janus kinase inhibitor treatment-naïve patients with myelofibrosis: results of the MANIFEST-2 randomized, double-blind, phase 3 study. Presentated at: 65th ASH Annual Meeting & Exposition.San Diego, CA, USA, 9–12 December 2023 ( Oral 628).
  • Mesa RA , VannucchiAM , MeadAet al. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol.4(5), e225–e236 (2017).
  • Mascarenhas J , HoffmanR , TalpazMet al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol.4(5), 652–659 (2018).
  • Gale RP , BarosiG , BarbuiTet al. What are RBC-transfusion-dependence and -independence? Leuk. Res. 35(1), 8–11 (2011).
  • Verstovsek S , OhS , KiladijianJ-Jet al. Transfusion independence response as a potential surrogate for overall survival in JAKi-experienced patients with myelofibrosis from MOMENTUM. Presented at: 64th ASH Annual Meeting & Exposition.New Orleans, LA, USA, 10–13 December 2022 ( Poster 3028).
  • Oh S , MesaR , HarrisonCet al. Retrospective analysis of anemia benefit of pacritinib from the PERSIST-2 trial. Presented at: 10th Annual Meeting of the Society of Hematologic Oncology.Houston, TX, USA, 28 September– 1 October 2022 ( Poster MPN-145).
  • Fenaux P , PlatzbeckerU , MuftiGJet al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N. Engl. J. Med.382(2), 140–151 (2020).
  • Salinas Cisneros G , TheinSL. Recent advances in the treatment of sickle cell disease. Front. Physiol.11, 435 (2020).
  • Cappellini MD , ViprakasitV , TaherATet al. A phase 3 trial of luspatercept in patients with transfusion-dependent beta-thalassemia. N. Engl. J. Med.382(13), 1219–1231 (2020).
  • Singh AK , CarrollK , McMurrayJJVet al. Daprodustat for the treatment of anemia in patients not undergoing dialysis. N. Engl. J. Med.385(25), 2313–2324 (2021).
  • Singh AK , CarrollK , PerkovicVet al. Daprodustat for the treatment of anemia in patients undergoing dialysis. N. Engl. J. Med.385(25), 2325–2335 (2021).
  • Jesduvroq (daprodustat) . Prescribing information. GlaxoSmithKline; 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jesduvroq/pdf/JESDUVROQ-PI-MG.PDF (Accessed 24October2023).
  • Reblozyl (luspatercept-aamt) . Prescribing information. Bristol Myers Squibb; 2022. https://packageinserts.bms.com/pi/pi_reblozyl.pdf (Accessed 24October2023).
  • Tefferi A , CervantesF , MesaRet al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood122(8), 1395–1398 (2013).
  • Chifotides HT , VerstovsekS , BoseP. Association of myelofibrosis phenotypes with clinical manifestations, molecular profiles, and treatments. Cancers (Basel).15(13), 3331 (2023).
  • Altman DG , RoystonP. The cost of dichotomising continuous variables. BMJ.332(7549), 1080 (2006).
  • Karakochuk CD , HessSY , MoorthyDet al. Measurement and interpretation of hemoglobin concentration in clinical and field settings: a narrative review. Ann. NY Acad. Sci.1450(1), 126–146 (2019).
  • Coskun A , CarobeneA , KilercikMet al. Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects. Clin. Chem. Lab. Med.56(8), 1309–1318 (2018).
  • Lippi G , Lima-OliveiraG , SalvagnoGLet al. Influence of a light meal on routine haematological tests. Blood Transfus.8(2), 94–99 (2010).
  • Roubinian NH , PlimierC , WooJPet al. Effect of donor, component, and recipient characteristics on hemoglobin increments following red blood cell transfusion. Blood134(13), 1003–1013 (2019).
  • Mascarenhas J , GerdsA , KiladijianJet al. PACIFICA: a randomized, controlled Phase III study of pacritinib versus physician’s choice in patients with primary or secondary myelofibrosis and severe thrombocytopenia. Presented at: 64th ASH Annual Meeting & Exposition.New Orleans, LA, USA, 10–13 December 2022 ( Poster 4316).
  • Mesa R , HarrisonC , OhSTet al. Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 Phase III trials of momelotinib in patients with myelofibrosis. Leukemia.36(9), 2261–2268 (2022).
  • Harrison C , MesaR , TalpazMet al. Reduction in red blood cell transfusion burden: a novel longitudinal time-dependent analysis in patients with transfusion-dependent myelofibrosis treated with momelotinib. Presented at: EHA2023 Hybrid Congress.Frankfurt, Germany, 8–11 June 2023 ( Poster P1044).
  • Mesa RA , PalandriF , VerstovsekSet al. Impact of transfusion burden on health-related quality of life (HRQOL) and functioning in patients (pts) with myelofibrosis (MF): post hoc analysis of SIMPLIFY-1 (S1) and -2 (S2). Presented at: ASCO Annual Meeting 2023.Chicago, IL, USA, 2–8 June 2023 ( Poster 7066).
  • Mesa RA , NiblackJ , WadleighMet al. The burden of fatigue and quality of life in myeloproliferative disorders (MPDs): an international Internet-based survey of 1179 MPD patients. Cancer109(1), 68–76 (2007).
  • Prochaska MT , ZhangH , BabajideR , MeltzerDO. The effect of red blood cell transfusion on fatigability after hospital discharge. Blood Adv.4(22), 5690–5697 (2020).