ASH 2019 Highlights

CME

New Insights in Hematologic Malignancies and Disorders: Independent Conference Coverage of the 2019 ASH Annual Meeting

Physicians : maximum of 1.00 AMA PRA Category 1 {Credit}

Released: March 17, 2020

Expiration: March 16, 2021

Jeffrey P. DONOTUSESharman
Jeffrey P. DONOTUSESharman, MD
Rami S. Komrokji
Rami S. Komrokji, MD
Sagar Lonial
Sagar Lonial, MD, FACP
Sujit Sheth
Sujit Sheth, MD
Eunice S. Wang
Eunice S. Wang, MD

Activity

Progress
1
Course Completed

References

  1. Sharman JP, Banerji V, Fogliatto LM, et al. ELEVATE TN: Phase 3 study of acalabrutinib combined with obinutuzumab (O) or alone vs O plus chlorambucil (Clb) in patients (Pts) with treatment-naive chronic lymphocytic leukemia (CLL). Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 31.
  2. Ghia P, Pluta A, Wach M, et al. ASCEND phase 3 study of acalabrutinib vs investigator’s choice of rituximab plus idelalisib (IDR) or bendamustine (BR) IN patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Program and abstracts of the 2019 European Hematology Association Annual Meeting; June 13-16, 2019; Amsterdam, The Netherlands. Abstract LB2606.
  3. ClinicalTrials.gov. Study of acalabrutinib (ACP-196) versus ibrutinib in previously treated subjects with high risk CLL. Available at: https://clinicaltrials.gov/ct2/show/NCT02477696. Accessed March 3, 2020.
  4. Blum KA, Polley M-Y, Jung S-H, et al. Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high-risk follicular lymphoma: CALGB 50904 (Alliance). Cancer. 2019;125:3378.
  5. Tam CS, Siddiqi T, Allan JN, et al. Ibrutinib plus venetoclax for first-line treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): results from the MRD cohort of the phase 2 CAPTIVATE study. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 35.
  6. ClinicalTrials.gov. A randomized, open-label, phase 3 study of the combination of ibrutinib plus venetoclax versus chlorambucil plus obinutuzumab for the first-line treatment of subjects with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Available at https://clinicaltrials.gov/ct2/show/NCT03462719. Accessed March 3, 2020.
  7. Siddiqi T, Soumerai JD, Dorritie KA, et al. Rapid undetectable MRD (uMRD) responses in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treated with lisocabtagene maraleucel (liso-cel), a CD19-directed CAR T cell product: updated results from Transcend CLL 004, a phase 1/2 study including patients with high-risk disease previously treated with ibrutinib. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 503.
  8. Schuster SJ, Bartlett NL, Assouline S, et al. Mosunetuzumab induces complete remissions in poor prognosis non-Hodgkin lymphoma patients, including those who are resistant to or relapsing after chimeric antigen receptor T-cell therapies, and is active in treatment through multiple lines. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 6.
  9. Mato AR, Flinn IW, Pagel JM, et al. Results from a first-in-human, proof-of-concept phase 1 trial in pretreated B-cell malignancies for Loxo-305, a next-generation, highly selective, non-covalent BTK inhibitor. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 501.
  10. Röllig C, Kramer M, Schliemann C, et al. Time from diagnosis to treatment does not affect outcomes in intensively treated patients with newly diagnosed acute myeloid leukemia. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 13.
  11. DiNardo C, Schuh AC, Stein EM, et al. Enasidenib plus azacitidine significantly improves complete remission and overall response compared with azacitidine alone in patient with newly diagnosed AML with isocitrate dehydrogenase 2 mutations. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 643.
  12. Aboudalle I, Konopleva MY, Kadia TM, et al. A phase Ib/II study of the BCL-2 inhibitor venetoclax in combination with standard intensive AML induction/consolidation therapy with FLAG-IDA in patients with newly diagnosed or relapsed/refractory AML. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 176.
  13. Wei AH, et al. The QUAZAR AML-001 maintenance trial. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract LBA_3.
  14. Foran JM, Sun Z, Claxton DF, et al. Maintenance decitabine improves disease-free and overall survival after intensive therapy for acute myeloid leukemia in older adults, particularly in FLT3-ITD-negative patients. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 115.
  15. Maiti A, Rausch CR, Cortes JE, et al. Outcomes of relapsed or refractory acute myeloid leukemia after frontline hypomethylating agent with venetoclax regimens. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 738.
  16. Chiaretti S, Bassan R, Vitale A, et al. Dasatinib-blinatumomab combination for the front-line treatment of adult Ph+ ALL patients. Updated results of the Gimema LAL2116 D-Alba trial. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 740.
  17. Short NJ, Kantarjian HK, Ravandi F, et al. Long-term safety and efficacy of hyper-CVAD plus ponatinib as frontline therapy for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 283.
  18. Brown PA, Ji L, Xu X, et al. A randomized phase 3 trial of blinatumomab vs chemotherapy as post-reinduction therapy in high and intermediate risk (HR/IR) first relapse of B-acute lymphoblastic leukemia (B-ALL) in children and adolescents/young adults (AYAs) demonstrates superior efficacy and tolerability of blinatumomab: a report from Children’s Oncology Group Study AALL1331. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract LBA-1.
  19. Lacayo NJ, Pullarkat VA, Stock W, et al. Safety and efficacy of venetoclax in combination with navitoclax in adult and pediatric relapsed/refractory acute lymphoblastic leukemia and lymphoblastic lymphoma. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 285.
  20. Gerds AT, Vannucchi AM, Passamonti F, et al. A phase 2 study of luspatercept in patients with myelofibrosis-associated anemia. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 557.
  21. Fenaux P, Platzbecker U, Mufti G, et al. The Medalist trial: results of a phase 3, randomized, double-blind, placebo-controlled study of luspatercept to treat anemia in patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS) who require red blood cell transfusions. Program and abstracts of the 2018 American Society of Hematology Annual Meeting; December 1-4, 2018; San Diego, California. Abstract 1.
  22. Fenaux P, Mufti GJ, Buckstein RJ, et al. Assessment of longer-term efficacy and safety in the phase 3, randomized, double-blind, placebo-controlled MEDALIST trial of luspatercept to treat anemia in patients (Pts) with revised International Prognostic Scoring System (IPSS-R) very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS) who require red blood cell (RBC) transfusions. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 841.
  23. Cluzeau T, Sebert M, Rahme R, et al. APR-246 combined with azacitidine (AZA) in TP53 mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). A phase 2 study by the Groupe Francophone des Myélodysplasies (GFM). Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 677.
  24. Sallman DA, DeZern AE, Garcia-Manero G, et al. Phase 2 results of APR-246 and azacitidine (AZA) in patients with TP53 mutant myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML). Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 676.
  25. ClinicalTrials.gov. APR-246 & azacitidine for the treatment of TP53 mutant myelodysplastic syndromes (MDS). Available at: https://clinicaltrials.gov/ct2/show/NCT03745716. Accessed March 3, 2020.
  26. Zeidan AM, Pollyea DA, Garcia JS, et al. A phase 1b study evaluating the safety and efficacy of venetoclax as monotherapy or in combination with azacitidine for the treatment of relapsed/refractory myelodysplastic syndrome. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 565.
  27. Sallman DA, Asch AS, Al Malki MM, et al. The first-in-class anti-CD47 antibody magrolimab (5F9) in combination with azacitidine is effective in MDS and AML patients: ongoing phase 1b results. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 569.
  28. Lonial S, Jacobus SJ, Weiss M, et al. E3A06: randomized phase III trial of lenalidomide versus observation alone in patients with asymptomatic high-risk smoldering multiple myeloma. Program and abstracts of the 2019 American Society of Clinical Oncology Annual Meeting; May 31 - June 4, 2019; Chicago, Illinois. Abstract 8001.
  29. Mateos MV, et al. Curative strategy (GEM-CESAR) for high-risk smoldering myeloma (SMM): carfilzomib, lenalidomide and dexamethasone (KRd) as induction followed by HDT-ASCT, consolidation with KRd and maintenance with Rd. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 781.
  30. Mateos M-V, Hernandez M-T, Giraldo P, et al. lenalidomide plus dexamethasone versus observation in patients with high-risk smouldering multiple myeloma (QuiRedex): long-term follow-up of a randomised, controlled, phase 3 trial. Lancet Oncol. 2016;17:1127-1136.
  31. Voorhees PM, Kaufman JL, Laubach JP, et al. Depth of response to daratumumab, lenalidomide, bortezomib, and dexamethasone improves over time in patients with transplant-eligible newly diagnosed multiple myeloma: Griffin study update. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 691.
  32. Moreau P, Zweegman S, Perrot A, et al. Evaluation of the prognostic value of positron emission tomography-computed tomography (PET-CT) at diagnosis and follow-up in transplant-eligible newly diagnosed multiple myeloma (TE NDMM) patients treated in the phase 3 Cassiopeia study: results of the Cassiopet companion study. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 692.
  33. Costa L, LJ, Chhabra S, Godby KN, et al. Daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd) induction, autologous transplantation and post-transplant, response-adapted, measurable residual disease (MRD)-based Dara-Krd consolidation in patients with newly diagnosed multiple myeloma (NDMM). Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 860.
  34. Mateos MV, Cavo M, Blade J, et al. Daratumumab plus bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone in patients with transplant-ineligible newly diagnosed multiple myeloma: overall survival in Alcyone. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 859.
  35. Puig N, Hernandez MT, Dachs LR, et al. Randomized trial of lenalidomide and dexamethasone versus clarythromycin, lenalidomide and dexamethasone as first line treatment in patients with multiple myeloma not candidates for autologous stem cell transplantation: results of the GEM-Claridex. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 694.
  36. Kapoor P, et al. Phase 2 trial of daratumumab, ixazomib, lenalidomide and modified dose dexamethasone in patients with newly diagnosed multiple myeloma. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 864.
  37. Usmani SZ, Quach H, Mateos M-V, et al. LBA-6: Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma (RRMM): primary analysis results from the randomized, open-label, phase 3 study CANDOR. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract LBA6.
  38. Madduri D, Usmani SZ, Jagannath S, et al. Results from CARTITUDE-1: a phase 1b/2 S-study of JNJ-4528, a CAR-T cell therapy directed against B-cell maturation antigen (BCMA), in patients with relapsed and/or refractory multiple myeloma (R/R MM). Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 577.
  39. Wang B-Y, Zhao W-H, Liu J, et al. Long-term follow-up of a phase 1, first-in-human open-label study of LCAR-B38M, a structurally differentiated chimeric antigen receptor T (CAR-T) cell therapy targeting B-cell maturation antigen (BCMA), in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 579.
  40. Costa L, Wong SW, Bermudez A, et al. First clinical study of the B-cell maturation antigen (BCMA) 2+1 T cell engager (TCE) CC-93269 in patients (Pts) with relapsed/refractory multiple myeloma (RRMM): interim results of a phase 1 multicenter trial. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 143.
  41. Chen C, Bahlis N, Gasparetto C, et al. Selinexor, pomalidomide, and dexamethasone (SPd) in patients with relapsed or refractory multiple myeloma. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 141.
  42. Harrison S, Cavo M, De La Rubia J, et al. T(11;14) and high BCL2 expression are predictive biomarkers of response to venetoclax in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma: biomarker analyses from the phase 3 Bellini study. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 142.
  43. Kaufman J, Gasparetto C, Schjesvold FH, et al. Phase I/II study evaluating the safety and efficacy of venetoclax in combination with dexamethasone as targeted therapy for patients with t(11;14) relapsed/refractory multiple myeloma. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 926.
  44. Bahlis N, et al. First analysis from a phase 1/2 study of venetoclax in combination with daratumumab and dexamethasone, +/- bortezomib, in patients with relapsed/refractory multiple myeloma. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 925.
  45. Crofford LJ, Nyhoff L, Sheehan J, Kendall P. The role of Bruton’s tyrosine kinase in autoimmunity and implications for therapy. Expert Rev Clin Immunol. 2017;12:763.
  46. Tsang M, Parikh SA. A concise review of autoimmune cytopenias in chronic lymphocytic leukemia. Curr Hematol Malig Rep. 2017;12:29-38.
  47. Kuter DJ, Boccia RV, Lee EJ, et al. Phase I/II, open-label, adaptive study of oral Bruton tyrosine kinase inhibitor PRN1008 in patients with relapsed/refractory primary or secondary immune thrombocytopenia. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 87.
  48. Langrish CL, Bradshaw JM, Owens TD, et al. PRN1008, a reversible covalent BTK inhibitor in clinical development for immune thrombocytopenic purpura. Program and abstracts of the 2017 American Society of Hematology Annual Meeting; December 9-12, 2017; Atlanta, Georgia. Abstract 1052.
  49. Al-Samkari H, Kuter DJ. Optimal use of thrombopoietin receptor agonists in immune thrombocytopenia. Ther Adv Hematol. 2019;Apr 11:Epub ahead of print.
  50. Broome CM, Roth A, Kuter DJ, et al. Inhibition of the classical pathway of complement with sutimlimab in chronic immune thrombocytopenic purpura patients without adequate response to two or more prior therapies. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 898.
  51. Thai L-H. Long-term complications after splenectomy in adult chronic immune thrombocytopenia with a minimum follow-up of 10 years: first results from a single-center case-control study in 140 patients with primary ITP. Program and abstracts of the 2014 American Society of Hematology Annual Meeting; December 6-9, 2014; San Francisco, California. Abstract 232.
  52. Avatrombopag package insert. Durham, NC: Dova Pharmaceuticals Inc.; 2019.
  53. Jurczak W, Chojnowski K, Mayer J, et al. Avatrombopag, a novel oral thrombopoietin receptor agonist, demonstrates superiority to placebo for the treatment of chronic immune thrombocytopenic purpura in a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Program and abstracts of the 2017 American Society of Hematology Annual Meeting; December 9-12, 2017; Atlanta, Georgia. Abstract 17.
  54. Al-Samkari HT, Aggarwal K, Vredenburg M, et al. Long-term response rates in patients with chronic immune thrombocytopenia treated with avatrombopag: additional analyses from a phase 3 study and its extension phase. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 2356.
  55. Röth. Inhibition of complement C1s with sutimlimab in patients with cold agglutinin disease (CAD): results from the phase 3 Cardinal study. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract LBA-2.
  56. Berentsen S, Roth A, Randen U, et al. Cold agglutinin disease: current challenges and future prospects. J Blood Med. 2019;10:93.
  57. Luspatercept package insert. Summit, NJ: Celgene Corporation; 2019.
  58. Esrick EB, Achebe M, Armant M, et al. Validation of BCL11A as therapeutic target in sickle cell disease: results from the adult cohort of a pilot/feasibility gene therapy trial inducing sustained expression of fetal hemoglobin using post-transcriptional gene silencing. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract LBA-5.
  59. ClinicalTrials.gov. A phase 1/2 study to evaluate the safety and efficacy of a single dose of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (CTX001) in subjects with severe sickle cell disease. Available at: https://clinicaltrials.gov/ct2/show/NCT03745287. Accessed March 3, 2020.
  60. Ribeil J-A, Hacein-Bey-Abina S, Payen E, et al. Gene therapy in a patient with sickle cell disease. N Engl J Med. 2017;376:848.
  61. Lal A, Locatelli F, Kwitkowski JL, et al. Northstar-3: interim results from a phase 3 study evaluating LentiGlobin gene therapy in patients with transfusion-dependent β-thalassemia and either a β0 or IVS-I-110 mutation at both alleles of the HBB gene. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 815.
  62. Thompson AA, Walters MC, Kwitakowski J, et al. gene therapy in patients with transfusion-dependent β-Thalassemia. N Engl J Med. 2018;378:1479.
  63. Locatelli F, Thompson AA, Hongeng S, et al. Safety and efficacy of lentiglobin gene therapy in patients with transfusion-dependent B-thalassaemia and non-B0/B0 genotypes in the phase 3 Northstar-2 study. Program and abstracts of the 2019 European Hematology Association annual meeting; June 13-16, 2019; Amsterdam, The Netherlands. Abstract S1632.
  64. Cappellini MD, Viprakasit V, Taher A, et al. The Believe trial: results of a phase 3, randomized, double-blind, placebo-controlled study of luspatercept in adult beta-thalassemia patients who require regular red blood cell (RBC) transfusions. Program and abstracts of the 2018 American Society of Hematology Annual Meeting; December 1-4, 2018; San Diego, California. Abstract 163.
  65. Viprakasit V, Taher AT, Hermine O, et al. Evaluating luspatercept responders in the phase 3, randomized, double-blind, placebo-controlled BELIEVE trial of luspatercept in adult-thalassemia patients who require regular red blood cell transfusions. Program and abstracts of the 2019 American Society of Hematology Annual Meeting; December 7-12, 2019; Orlando, Florida. Abstract 3545.