Hematology 2021: MDS/MPN

CME

Key Studies in Myelodysplastic Syndromes and Myeloproliferative Neoplasms: Independent Conference Coverage of the 2021 ASH Annual Meeting

Physicians: Maximum of 1.25 AMA PRA Category 1 Credits

Released: May 11, 2022

Expiration: May 10, 2023

Amy E. DeZern
Amy E. DeZern, MD, MHS
Srdan Verstovsek
Srdan Verstovsek, MD, PhD

Activity

Progress
1
Course Completed

  1. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391-2405.
  2. Jackson CC, Medeiros LJ, Miranda RN. 8p11 myeloproliferative syndrome: a review. Hum Pathol. 2010;41:461-476.
  3. Gotlib J, Kiladjian J-J, Vannucchi A, et al. A phase 2 study of pemigatinib (FIGHT-203; INCB054828) in patients with myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement (MLNFGFR1). Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021. Abstract 385.
  4. Spivak. Advances in polycythemia vera and lessons for acute leukemia. Best Pract Res Clin Hematol. 2021;34:101330.
  5. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: myeloproliferative neoplasms. v.2.2021. www.nccn.org. Accessed April 29, 2022.
  6. Ropeginterferon [prescribing information]. Burlington, MA: PharmaEssentia; 2021.
  7. Gisslinger H, Klade C, Georgiev P, et al. Polycythemia vera patients respond better to ropeginterferon alfa-2b than HU/BAT irrespective of pretreatment or mutational status; results from 5 years' treatment in a randomized, controlled setting in the PROUD-PV/CONTINUATION-PV trials. Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021. Abstract 3660.
  8. Ginzburg YZ, Feola M, Zimran E, et al. Dysregulated iron metabolism in polycythemia vera: etiology and consequences. Leukemia. 2018;32:2105.
  9. Hoffman R, Kremyanskaya M, Ginzburg Y, et al. Rusfertide (PTG-300) controls hematocrit levels and essentially eliminates phlebotomy requirement in polycythemia vera patients. Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021. Abstract 388.
  10. Komrokji RS, Seymour JF, Roberts AW, et al. Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Blood. 2015;125:2649-2655.
  11. Mesa R, Vannucchi A, Mead A, et 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. 2017;4:e225-e236.
  12. Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018;4:652-659.
  13. Palmer JM, Mesa RA, Oh ST, et al. The impact of pacritinib on myelofibrosis symptoms in patients with moderate and severe thrombocytopenia: a retrospective analysis of patients in the PERSIST-2 study. Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021. Abstract 3628.
  14. Albrecht BK, Gehling VS, Hewitt MC, et al. Identification of a benzoisoxazoloazepine inhibitor (CPI-0610) of the bromodomain and extra-terminal (BET) family as a candidate for human clinical trials. J Med Chem. 2016;59:1330-1339.
  15. Kremyanskaya M, Mascarenhas J, Palandri F, et al. Pelabresib (CPI-0610) monotherapy in patients with myelofibrosis—update of clinical and translational data from the ongoing manifest trial. Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021. Abstract 141.
  16. Verstovsek S, Salama ME, Mascarenhas J, et al. Disease-modifying potential of BET inhibitor pelabresib (CPI-0610) as demonstrated by improvements in bone marrow function and clinical activity in patients with myelofibrosis—preliminary data. Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021. Abstract 2568.
  17. Bose P, Masarova L, Pemmaraju N, et al. Final results of a phase 2 study of sotatercept (ACE-011) for anemia of MPN-associated myelofibrosis. Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021. Abstract 144.
  18. Luspatercept [prescribing information]. Summit, NJ: Celgene; 2020.
  19. Lu M, Wang X, Li Y, Tripodi J, Mosoyan G, Mascarenhas J, et al. Combination treatment in vitro with Nutlin, a small-molecule antagonist of MDM2, and pegylated interferon-alpha 2a specifically targets JAK2(V617F)-positive polycythemia vera cells. Blood. 2012;120:3098-4105.
  20. Vachhani P, Lange A, Delgado RG, et al. Potential disease-modifying activity of navtemadlin (KRT-232), a first-in-class MDM2 inhibitor, correlates with clinical benefits in relapsed/refractory myelofibrosis (MF). Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021. Abstract 3581.
  21. Selinexor [prescribing information]. Newton, MA: Karyopharm; 2019.
  22. Tantravahi SK, Kim SJ, Sundar D, et al. A phase 2 study to evaluate the efficacy and safety of selinexor in patients with myelofibrosis refractory or intolerant to JAK inhibitors. Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021. Abstract 143.
  23. Yap TA, Lakhani NJ, Araujo DV, et al. AVID200, first-in-class TGF-beta 1 and 3 selective and potent inhibitor: Safety and biomarker results of a phase I monotherapy dose-escalation study in patients with advanced solid tumors. Presented at: 2020 American Society of Clinical Oncology; May 29-31, 2020. Abstract 3587.
  24. Mascarenhas J, Kosiorek HE, Bhave R, et al. Treatment of myelofibrosis patients with the TGF-β 1/3 inhibitor AVID200 (MPN-RC 118) induces a profound effect on platelet production. Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021. Abstract 142.
  25. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079-2088.
  26. Greenberg PL, Tuechleer H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes Blood. 2012;120:2454-2465.
  27. Bernard E, Tuechler H, Greenberg PL, et al. Molecular international prognosis scoring system for myelodysplastic syndromes. Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021; December 11-14, 2021. Abstract
  28. Bernard E, Nannya Y, Hasserjian RP, et al. Implications of TP53 allelic state for genome stability, clinical presentation, and outcomes in myelodysplastic syndromes. Nat Med. 2020;26:1549-1556.
  29. Fenaux P, Morel P, Rose C, et al. Prognostic factors in adult de novo myelodysplastic syndromes treated by intensive chemotherapy. Br J Haematol. 1991;77:497-501.
  30. Estey EH, Kantarjian HM, O’Brien S, et al. High remission rate, short remission duration in patients with refractory anemia with excess blasts (RAEB) in transformation (RAEB-t) given acute myelogenous leukemia (AML)-type chemotherapy in combination with granulocyte-CSF (G-CSF). Cytokines Mol Ther. 1995;1:21-28.
  31. Verbeek W, Wörmann B, Koch P, et al. S-HAM induction chemotherapy with or without GM-CSF in patients with high-risk myelodysplastic syndromes. Ann Hematol. 1997;74:205-208.
  32. Wattel E, De Botton S, Luc Laï J, et al. Long-term follow-up of de novo myelodysplastic syndromes treated with intensive chemotherapy: incidence of long-term survivors and outcome of partial responders. Br J Haematol. 1997;98:983-991.
  33. Estey EH, Thall PF, Cortes JE, et al. Comparison of idarubicin + ara-C-, fludarabine + ara-C-, and topotecan + ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts. Blood. 2001;98:3575-3583.
  34. Prébet T, Ducastelle S, Debotton S, et al. A phase II study of intensive chemotherapy with fludarabine, cytarabine, and mitoxantrone in P glycoprotein-negative high-risk myelodysplastic syndromes. Hematol J. 2004;5:209-215.
  35. Kantarjian H, O’Brien S, Cortes J, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006;106:1090-1098.
  36. Knipp S, Hildebrand B, Kündgen A, et al. Intensive chemotherapy is not recommended for patients aged >60 years who have myelodysplastic syndromes or acute myeloid leukemia with high-risk karyotypes. Cancer. 2007;110:345-352.
  37. Lancet JE, Uy GL, Newell LF, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8:e481-e491.
  38. Lin TL, Uy GL, Wieduwilt MJ, et al. Subanalysis of patients with secondary acute myeloid leukemia (sAML) with refractory anemia with excess of blasts in transformation (RAEB-t) enrolled in a phase 3 study of CPX-351 versus conventional 7+3 cytarabine and daunorubicin. Presented at: 2017 American Society of Hematology annual meeting; December 9-12, 2017. Abstract 637.
  39. Peterlin P, Turlure P, Chevallier P, et al. CPX 351 as first line treatment in higher risk MDS. a phase II trial by the GFM. Presented at: 2021 American Society of Hematology annual meeting; December 11-16, 2021; December 11-14, 2021. Abstract
  40. Fenaux P, Giagounidis A, Selleslag D, et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with low-/intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 2011;118:3765-3776.
  41. Santini V, Almeida A, Giagounidis A, et al. Randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents. J Clin Oncol. 2016;34:2988-2996.
  42. Oliva EN, Alati C, Santini V, et al. Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial. Lancet Haematol. 2017;4:e127-e136.
  43. Tamari R, Schinke C, Bhagat T, et al. Eltrombopag can overcome the anti-megakaryopoietic effects of lenalidomide without increasing proliferation of the malignant myelodysplastic syndrome/acute myelogenous leukemia clone. Leuk Lymphoma. 2014;55:2901-2906.
  44. Gonzalez-Lugo JD, Kambhampati S, Yacoub A, et al. Lenalidomide and eltrombopag for treatment in low or intermediate risk myelodysplastic syndrome: result of a phase 2 study combination clinical trial. Presented at: 2021 American Society of Hematology annual meeting; December 11-14, 2021. Abstract
  45. Zeidan AM, Davidoff AJ, Long JB, et al. Comparative clinical effectiveness of azacitidine versus decitabine in older patients with myelodysplastic syndromes. Br J Haematol. 2016;175:829-840.
  46. Garcia JS, Wei AH, Borate U, et al. Safety, efficacy, and patient-reported outcomes of venetoclax in combination with azacitidine for the treatment of patients with higher-risk myelodysplastic syndrome: a phase 1b study. Presented at: 2020 American Society of Hematology annual meeting; December 5-8, 2020. Abstract
  47. Zeidan AM, Pollyea DA, Garcia JS, et al. A phase 1b study evaluating the safety and efficacy of venetoclax in combination with azacitidine for the treatment of relapsed/refractory myelodysplastic syndrome. Presented at: 2020 American Society of Hematology annual meeting; December 5-8, 2020. Abstract
  48. Komrokji RS, Al Ali N, Chan O, et al. Assessing the role of venetoclax in combination with hypomethylating agents in higher risk myelodysplastic syndromes. Presented at: 2021 American Society of Hematology annual meeting; December 11-14, 2021. Abstract
  49. Das M, Zhu C, Kuchroo VK. Tim-3 and its role in regulating anti-tumor immunity. Immunol Rev. 2017;276:97-111.
  50. Rezeai M, Tan J, Zeng C, et al. TIM-3 in leukemia; immune response and beyond. Front Oncol. 2021;11:753677.
  51. Brunner AM, Esteve J, Porkka K, et al. Efficacy and safety of sabatolimab (MBG453) in combination with hypomethylating agents (HMAs) in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS): Updated results from a phase 1b study. Presented at: 2020 American Society of Hematology annual meeting; December 5-8, 2020. Abstract
  52. Wei A, Esteve J, Porkka K, et al. Sabatolimab plus hypomethylating agents (Hmas) In Patients (Pts) with high-/very high-risk myelodysplastic syndrome (Hr/Vhr-Mds) and acute myeloid leukemia (Aml): subgroup analysis of a phase 1 study. Presented at: EHA Virtual Congress 2021; June 9-17, 2021. Abstract S168.
  53. Brunner AM, Esteve J, Porkka K, et al. Efficacy and safety of sabatolimab (MBG453) in combination with hypomethylating agents (HMAs) in patients (Pts) with very high/high-risk myelodysplastic syndrome (vHR/HR-MDS) and acute myeloid leukemia (AML): final analysis from a phase Ib study. Presented at: 2021 American Society of Hematology annual meeting; December 11-14, 2021. Abstract