Medscape InDiscussion: Myelofibrosis

What will the next decade bring for myelofibrosis care? Drs Jain and Pemmaraju explore futuristic therapies, earlier interventions, and smarter diagnostics. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002058. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Manipulating Hepcidin in Polycythemia Vera https://pubmed.ncbi.nlm.nih.gov/37383006/ Role of ASXL1 and TP53 Mutations in the Molecular Classification and Prognosis of Acute Myeloid Leukemias With Myelodysplasia-Related Changes https://pubmed.ncbi.nlm.nih.gov/25860933/ Cryptic KMT2A::AFDN Fusion Due to AFDN Insertion Into KMT2A in a Patient With Acute Monoblastic Leukemia https://pubmed.ncbi.nlm.nih.gov/40149468/ 8p11 Myeloproliferative Syndrome: A Review https://pubmed.ncbi.nlm.nih.gov/20226962/ What's Next? Clinical Trials in Myelofibrosis https://www.medscape.com/viewarticle/1002053 Artificial Intelligence-Based Morphological Fingerprinting of Megakaryocytes: A New Tool for Assessing Disease in MPN Patients https://pubmed.ncbi.nlm.nih.gov/32706893/ Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies https://pubmed.ncbi.nlm.nih.gov/37290996/ The Telomerase Inhibitor Imetelstat Differentially Targets JAK2V617F Versus CALR Mutant Myeloproliferative Neoplasm Cells and Inhibits JAK-STAT Signaling https://pubmed.ncbi.nlm.nih.gov/37941547/ A Novel Application of XPO1 Inhibition for the Treatment of Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/40454401/ BOREAS: A Global, Phase III Study of the MDM2 Inhibitor Navtemadlin (KRT-232) in Relapsed/Refractory Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/36416118/ Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial https://pubmed.ncbi.nlm.nih.gov/37126762/ Center for International Blood & Marrow Transplant Research (CIBMTR) https://cibmtr.org/ Donor Types and Outcomes of Transplantation in Myelofibrosis: A CIBMTR Study https://pubmed.ncbi.nlm.nih.gov/38916866/ Clearance of Driver Mutations After Transplantation for Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/39778169/ Development of a First-in-Class CAR-T Therapy Against Calreticulin-Mutant Neoplasms and Evaluation in the Relevant Human Tissue Environment https://ashpublications.org/blood/article/144/Supplement%201/871/531067/Development-of-a-First-in-Class-CAR-T-Therapy

Join Drs Tania Jain and Prithviraj Bose as they discuss the available JAK inhibitors and how they use them to treat myelofibrosis. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002056. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Primary Myelofibrosis https://emedicine.medscape.com/article/197954-overview JAK Inhibition for the Treatment of Myelofibrosis: Limitations and Future Perspectives https://pubmed.ncbi.nlm.nih.gov/32903304/ You Really Got a Hold on Me https://ashpublications.org/ashclinicalnews/news/6493/You-Really-Got-a-Hold-on-Me A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/22375971/ Overall Survival in the SIMPLIFY-1 and SIMPLIFY-2 Phase 3 Trials of Momelotinib in Patients With Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/35869266/ Biological Basis for Efficacy of Activin Receptor Ligand Traps in Myelodysplastic Syndromes https://pubmed.ncbi.nlm.nih.gov/31961337/ Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis (ODYSSEY) https://clinicaltrials.gov/study/NCT06517875 Biology and Therapeutic Targeting of Molecular Mechanisms in MPNs https://pubmed.ncbi.nlm.nih.gov/36534936/ Selinexor in Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors (ESSENTIAL) https://clinicaltrials.gov/study/NCT03627403 Selinexor Plus Ruxolitinib in JAK Inhibitor Treatment-Naïve Myelofibrosis: SENTRY Phase 3 Study Design https://pubmed.ncbi.nlm.nih.gov/39911057/ EHA 2023, Abstract 210: An Open-Label, Global, Phase (Ph) 1b/2 Study Adding Navtemadlin (Nvtm) to Ruxolitinib (Rux) in Patients (Pts) With Primary or Secondary Myelofibrosis (Mf) Who Have a Suboptimal Response to Rux https://library.ehaweb.org/eha/2023/eha2023-congress/387910/john.mascarenhas.an.open-label.global.phase.28ph29.1b.2.study.adding.navtemadlin.html Imetelstat in Intermediate-2 or High-Risk Myelofibrosis Refractory to JAK Inhibitor: IMpactMF Phase III Study Design https://pubmed.ncbi.nlm.nih.gov/35510486/ CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms https://pubmed.ncbi.nlm.nih.gov/26175413/ Ropeginterferon Alfa-2b (ROPEG) and Peginterferon Alfa-2a (PEG) at Low Dose With Response-Based Titration (LDRT) Have Comparable Efficacy and Tolerability in Polycythemia Vera (PV) https://ashpublications.org/blood/article/144/Supplement%201/4568/533799/Ropeginterferon-Alfa-2b-ROPEG-and-Peginterferon The Characteristics of CALR Mutations in Myeloproliferative Neoplasms: A Clinical Experience From a Tertiary Care Center in Qatar and a Literature Review https://pubmed.ncbi.nlm.nih.gov/38804886/ Pelabresib Plus Ruxolitinib for JAK Inhibitor-Naive Myelofibrosis: A Randomized Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/40065169/ TRANSFORM-1 Trial of Navitoclax in Combination With Ruxolitinib for Myelofibrosis Met Primary but Not Secondary Endpoint https://ashpublications.org/ashclinicalnews/news/7630/TRANSFORM-1-Trial-of-Navitoclax-in-Combination Randomized, Single-Blind, Multicenter Phase II Study of Two Doses of Imetelstat in Relapsed or Refractory Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/34138638/ Efficacy and Safety of Fedratinib in Patients With Myelofibrosis Previously Treated With Ruxolitinib (FREEDOM2): Results From a Multicentre, Open-Label, Randomised, Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/39265613/ Fedratinib in Patients With Myelofibrosis Previously Treated With Ruxolitinib: An Updated Analysis of the JAKARTA2 Study Using Stringent Criteria for Ruxolitinib Failure https://pubmed.ncbi.nlm.nih.gov/32129512/ Impact of TP53 on Outcome of Patients With Myelofibrosis Undergoing Hematopoietic Stem Cell Transplantation https://pubmed.ncbi.nlm.nih.gov/36940410/ SURPASS-ET: Phase III Study of Ropeginterferon Alfa-2b Versus Anagrelide as Second-Line Therapy in Essential Thrombocythemia https://pubmed.ncbi.nlm.nih.gov/35924546/ EXCEED-ET: A Single-Arm Multicenter Study to Assess the Efficacy, Safety, and Tolerability of Ropeginterferon alfa-2b-njft (P1101) in North American Adults With Essential Thrombocythemia https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS7088 Ropeginterferon alfa-2b Versus Standard Therapy for Polycythaemia Vera (PROUD-PV and CONTINUATION-PV): A Randomised, Non-inferiority, Phase 3 Trial and Its Extension Study https://pubmed.ncbi.nlm.nih.gov/32014125/ Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial https://pubmed.ncbi.nlm.nih.gov/37126762/

Join Drs Tania Jain and Krisstina Gowin as they discuss the role integrative medicine plays in the treatment of myelofibrosis. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002054. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Myeloproliferative Neoplasm (MPN) Symptom Assessment Form Total Symptom Score: Prospective International Assessment of an Abbreviated Symptom Burden Scoring System Among Patients With MPNs https://pubmed.ncbi.nlm.nih.gov/23071245/ The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): International Prospective Validation and Reliability Trial in 402 Patients https://pubmed.ncbi.nlm.nih.gov/21536863/ Comprehensively Understanding Fatigue in Patients With Myeloproliferative Neoplasms https://pubmed.ncbi.nlm.nih.gov/26670597/ The Hallmarks of Cancer https://pubmed.ncbi.nlm.nih.gov/10647931/ Primary Prevention of Cardiovascular Disease With a Mediterranean Diet Supplemented With Extra-Virgin Olive Oil or Nuts https://pubmed.ncbi.nlm.nih.gov/29897866/ The NUTRIENT Trial (NUTRitional Intervention among myEloproliferative Neoplasms): Feasibility Phase https://pubmed.ncbi.nlm.nih.gov/37214789/ Lifestyle Factors and Cancer: A Narrative Review https://pubmed.ncbi.nlm.nih.gov/38468817/ Online Yoga in Myeloproliferative Neoplasm Patients: Results of a Randomized Pilot Trial to Inform Future Research https://pubmed.ncbi.nlm.nih.gov/31174535/ American Cancer Society Guideline for Diet and Physical Activity for Cancer Prevention https://pubmed.ncbi.nlm.nih.gov/32515498/ Integrative Oncology Care of Symptoms of Anxiety and Depression in Adults With Cancer: Society for Integrative Oncology-ASCO Guideline https://pubmed.ncbi.nlm.nih.gov/37582238

Join Drs Tania Jain and Gabriela Hobbs as they discuss their views on the future of research and patient care in myelofibrosis. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/999598. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Risk Stratification in Myelofibrosis: Which Model Should You Use? https://www.medscape.com/viewarticle/999593 MIPSS70: Mutation-Enhanced International Prognostic Score System for Transplantation-Age Patients With Primary Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/29226763/ GIPSS: Genetically Inspired Prognostic Scoring System for Primary Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/29654267/ DIPSS Plus: A Refined Dynamic International Prognostic Scoring System for Primary Myelofibrosis That Incorporates Prognostic Information From Karyotype, Platelet Count, and Transfusion Status https://pubmed.ncbi.nlm.nih.gov/21149668/ A Prognostic Model to Predict Survival After 6 Months of Ruxolitinib in Patients With Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/35130339/ Broad Next-Generation Integrated Sequencing of Myelofibrosis Identifies Disease-Specific and Age-Related Genomic Alterations https://pubmed.ncbi.nlm.nih.gov/38386293/ The Role of Mutated Calreticulin in the Pathogenesis of BCR-ABL1-Negative Myeloproliferative Neoplasms https://pubmed.ncbi.nlm.nih.gov/39337361/ Myeloproliferative Neoplasm (MPN) Symptom Assessment Form Total Symptom Score: Prospective International Assessment of an Abbreviated Symptom Burden Scoring System Among Patients With MPNs https://pubmed.ncbi.nlm.nih.gov/23071245/

Join Drs Tania Jain and Raajit Rampal as they discuss TP53, post-MPN AML, and high-risk MPNs in the context of myelofibrosis. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/999596. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Primary Myelofibrosis https://emedicine.medscape.com/article/197954-overview Myeloproliferative Neoplasms https://www.ncbi.nlm.nih.gov/books/NBK531464/ Acute Myeloid Leukemia Following Myeloproliferative Neoplasms: A Review of What We Know, What We Do Not Know, and Emerging Treatment Strategies https://pubmed.ncbi.nlm.nih.gov/36632576/ Updated Safety and Efficacy Data From the Phase 3 MANIFEST-2 Study of Pelabresib in Combination With Ruxolitinib for JAK Inhibitor Treatment-Naïve Patients With Myelofibrosis https://meetings.asco.org/abstracts-presentations/231688 Next Generation Sequencing in MPNs. Lessons From the Past and Prospects for Use as Predictors of Prognosis and Treatment Responses https://pubmed.ncbi.nlm.nih.gov/32781570/ The MDM2 Antagonist Idasanutlin in Patients With Polycythemia Vera: Results From a Single-Arm Phase 2 Study https://ashpublications.org/bloodadvances/article/6/4/1162/483223/The-MDM2-antagonist-idasanutlin-in-patients-with Venetoclax With Azacitidine or Decitabine in Blast-Phase Myeloproliferative Neoplasm: A Multicenter Series of 32 Consecutive Cases https://pubmed.ncbi.nlm.nih.gov/33844862/ Association of Factors Influencing Selection of Upfront Hematopoietic Cell Transplantation Versus Nontransplantation Therapies in Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/33798769/ Genomic Analysis of Primary and Secondary Myelofibrosis Redefines the Prognostic Impact of ASXL1 Mutations: a FIM Study https://pubmed.ncbi.nlm.nih.gov/33666653/ TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes https://pubmed.ncbi.nlm.nih.gov/27959731/ Safety and Efficacy of Combined Ruxolitinib and Decitabine in Accelerated and Blast-phase Myeloproliferative Neoplasms https://pubmed.ncbi.nlm.nih.gov/30563881/ Efficacy and Safety of Combination Therapies vs Monotherapy of Hypomethylating Agents in Accelerated or Blast Phase of Philadelphia Negative Myeloproliferative Neoplasms: a Systematic Review and Meta-analysis https://pubmed.ncbi.nlm.nih.gov/36644935/ Genomic and Functional Analysis of Leukemic Transformation of Myeloproliferative Neoplasms https://pubmed.ncbi.nlm.nih.gov/25516983/ BMP2/SMAD Pathway Activation in JAK2/p53-Mutant Megakaryocyte/Erythroid Progenitors Promotes Leukemic Transformation https://pubmed.ncbi.nlm.nih.gov/35421216/ Single-Cell Multi-omics Identifies Chronic Inflammation as a Driver of TP53-Mutant Leukemic Evolution https://pubmed.ncbi.nlm.nih.gov/37666991/

Join Drs Tania Jain and Aaron Gerds as they discuss the latest developments in clinical trials and investigational therapeutics for MPNs. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/999594. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Primary Myelofibrosis https://emedicine.medscape.com/article/197954-overview Myeloproliferative Neoplasms https://www.ncbi.nlm.nih.gov/books/NBK531464/ Bromodomain and Extraterminal (BET) Proteins: Biological Functions, Diseases, and Targeted Therapy https://pubmed.ncbi.nlm.nih.gov/37926722/ Long-Term Survival in Patients Treated With Ruxolitinib for Myelofibrosis: COMFORT-I and -II Pooled Analyses https://pubmed.ncbi.nlm.nih.gov/28962635/ Rampal RK, Grosicki S, Chraniuk S, et 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. Program and abstracts of the 65th American Society of Hematology Annual Meeting and Exposition; December 10, 2023; San Diego, California. Abstract 628. https://ash.confex.com/ash/2023/webprogram/Paper179141.html Pemmaraju N, Mead AJ, Somervaille T CP, et al.Transform-1: A randomized, double-blind, placebo-controlled, multicenter, international phase 3 study of navitoclax in combination with ruxolitinib versus ruxolitinib plus placebo in patients with untreated myelofibrosis. Program and abstracts of the 65th American Society of Hematology Annual Meeting and Exposition; December 10, 2023; San Diego, California. Abstract 620. https://ash.confex.com/ash/2023/webprogram/Paper173509.html Defining Disease Modification in Myelofibrosis in the Era of Targeted Therapy https://pubmed.ncbi.nlm.nih.gov/35499819/ A Prognostic Model to Predict Survival After 6 Months of Ruxolitinib in Patients With Myelofibrosis https://pubmed.ncbi.nlm.nih.gov/35130339/ Imetelstat in Patients With Lower-Risk Myelodysplastic Syndromes Who Have Relapsed or Are Refractory to Erythropoiesis-Stimulating Agents (IMerge): A Multinational, Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/38048786/