Hematology 2022: MDS and MPNs

CME

Key Studies in Myelodysplastic Syndromes and Myeloproliferative Neoplasms: Independent Conference Coverage of ASH 2022

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit

Released: March 16, 2023

Expiration: March 15, 2024

Srdan Verstovsek
Srdan Verstovsek, MD, PhD
Amer Zeidan
Amer Zeidan, MBBS, MHS

Activity

Progress
1
Course Completed
References

  1. Khoury JD, Solary E, Abla O, et al. The 5th Edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36:1703-1719.
  2. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140:1200-1228.
  3. Ball S, Singh AM, Ali NA, et al. A product of “clash of titans” or true reflection of disease biology? Validation of 2022 WHO and ICC classifications in a large dataset of patients with myelodysplastic syndrome. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 463.
  4. Bernard E, Tuechler H, Greenberg PL, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evidence. 2022;1:EVIDoa2200008.
  5. Sauta E, Robin M, Bersanelli M, et al. Real-world validation of Molecular International Prognostic Scoring System (IPSS-M) for myelodysplastic syndromes. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 464.
  6. Lenalidomide [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; 2022.
  7. López Cadenas F, Lumbreras E, González T, et al. Evaluation of lenalidomide (LEN) vs placebo in non-transfusion dependent low risk del (5q) MDS patients. Final results of Sintra-REV phase III international multicenter clinical trial. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 460.
  8. Steensma DP, Fenaux P, Van Eygen K, et al. Imetelstat achieves meaningful and durable transfusion independence in high transfusion-burden patients with lower-risk myelodysplastic syndromes in a phase II study. J Clin Oncol. 2021;39:48-56.
  9. Platzbecker U, Komrokji RS, Fenaux P, et al. Imetelstat achieved prolonged, continuous transfusion independence (TI) in patients with heavily transfused non-del (5q) lower-risk myelodysplastic syndrome (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESAs) within the IMerge phase 2 study. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 459.
  10. The ASCO Post. Phase III IMerge trial of imetelstat in lower-risk MDS. ascopost.com/news/january-2023/phase-iii-imerge-trial-of-imetelstat-in-lower-risk-mds. Accessed February 2, 2023.
  11. Schwartz S, Patel N, Longmire T, et al. Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor. Immunotherapy Advances. 2022;2:ltac019.
  12. 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 and Exposition; December 11-14, 2021. Abstract 244.
  13. Zeidan AM, Ando K, Rauzy O, et al. Primary results of Stimulus-MDS1: a randomized, double-blind, placebo-controlled phase II study of TIM-3 inhibition with sabatolimab added to hypomethylating agents (HMAs) in adult patients with higher-risk myelodysplastic syndromes (MDS). Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 853.
  14. Itzykson R, Santini V, Thepot S, et al. Decitabine versus hydroxyurea for advanced proliferative chronic myelomonocytic leukemia: results of a randomized phase III trial within the EMSCO network. J Clin Oncol. 2022;JCO2200437.
  15. Ruxolitinib [prescribing information]. Wilmington, DE: Incyte; 2022.
  16. Hunter AM, Newman H, Dezern AE, et al. Integrated human and murine clinical study establishes clinical efficacy of ruxolitinib in chronic myelomonocytic leukemia. Clin Cancer Res. 2021;27:6095-6105.
  17. Padron E, Tinsley-Vance SM, DeZern AE, et al. Efficacy and safety of ruxolitinib for treatment of symptomatic chronic myelomonocytic leukemia (CMML): results of a multicenter phase II clinical trial. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 457.
  18. Sallman DA, DeZern AE, Gayle AA, et al. Phase 1 results of the first-in-class CXCR1/2 inhibitor SX-682 in patients with hypomethylating agent failure myelodysplastic syndromes. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 855.
  19. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366:799-807.
  20. Chifotides HT, Bose P, Verstovsek S. Momelotinib: an emerging treatment for myelofibrosis patients with anemia. J Hematol Oncol. 2022;15:7.
  21. Asshoff M, Petzer V, Warr MR, et al. Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents. Blood. 2017;129:1-21.
  22. Oh ST, Mesa R, Harrison C, et al. Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis. Blood. 2022;140(suppl 1):1518-1521.
  23. Gerds AT, Mesa R, Vannucchi AM, et al. Updated results from the Momentum phase 3 study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with JAK inhibitor. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 627.
  24. Mesa RA, Gerds AT, Vannucchi A, et al. MOMENTUM: phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. Presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-6, 2022. Abstract 7002.
  25. Gerds AT, Bartalucci N, Assad A, et al. Targeting the PI3K pathway in myeloproliferative neoplasms. Expert Rev Anticancer Ther. 2022;22:835-843.
  26. Yacoub A, Borate U, Rampal RK, et al. Efficacy and safety of add-on parsaclisib to ruxolitinib therapy in myelofibrosis patients with suboptimal response to ruxolitinib: final results from a phase 2 study. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 236.
  27. Mascarenhas J, Kremyanskaya M, Patriarca A, et al. Pelabresib (CPI-0610) combined with ruxolitinib for JAK inhibitor treatment-naive patients with myelofibrosis: durability of response and safety beyond week 24. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 238.
  28. Verstovsek S, Salama, 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. Blood. 2021;138(suppl 1):2568.
  29. Sun Y, Han J, Wang Z, et al. Safety and efficacy of bromodomain and extra-terminal inhibitors for the treatment of hematological malignancies and solid tumors: a systematic study of clinical trials. Front Pharmacol. 2021;11:1-15.
  30. Verstovsek S, Komatsu N, Gill H, et al. SURPASS-ET: phase III study of ropeginterferon alfa-2b versus anagrelide as second-line therapy in essential thrombocytopenia. Future Oncol. 2022;18:2999-3009.
  31. Ropeginterferon alfa-2b-njft [prescribing information]. Burlington, MA: PharmaEssentia; 2021.
  32. Gill H, Au L, Yim R, et al. Efficacy and safety of ropeginterferon alfa-2b for pre-fibrotic primary myelofibrosis and DIPSS low/intermediate-1 risk myelofibrosis. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 629.
  33. Passamonti F, Foran JM, Tandra A, et al. The combination of navitoclax and ruxolitinib in JAK inhibitor-naive patients with myelofibrosis mediates responses suggestive of disease modification. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 237.
  34. Ali H, Kishtagari A, Maher K, et al. A phase 1, open-label, dose-escalation study of selinexor plus ruxolitinib in patients with treatment-naive myelofibrosis. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 1734.
  35. Heidel FH, Perkins AC, Reiter A, et al. Siremadlin, a human double minute-2 (HDM2) inhibitor, added to ruxolitinib after suboptimal response to ruxolitinib alone in patients with myelofibrosis: results from part 1 of the phase 1/2 Adore study. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 239.
  36. Guglielmelli P, Mora B, Gesullo F, et al. JAK2V617F molecular response to ruxolitinib in patients with PV and ET is associated with lower risk of progression to secondary myelofibrosis. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 741.
  37. Harrison CN, Mead AJ, Panchal A, et al. Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide. Blood. 2017;130:1889-1897.
  38. Leukemia & Lymphoma Society (LLS). Myelofibrosis facts. lls.org/sites/default/files/file_assets/FS14_Myelofibrosis_Fact%20Sheet_Final9.12.pdf. Accessed February 2, 2023.
  39. Barosi G, Mesa R, Finazzi G, et al. Revised response criteria for polycythemia vera and essential thrombocytopenia: an ELN and IWG-MRT consensus project. Blood. 2013;121:4778-4781.