Hematologic Malignancies Highlights: ASCO 2022

CME

Key Studies in Hematologic Malignancies: Independent Conference Coverage of the 2022 ASCO Annual Meeting

Physicians: Maximum of 1.50 AMA PRA Category 1 Credits

Released: September 13, 2022

Expiration: September 12, 2023

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1
Course Completed

References

  1. Smith CC, Lasater EA, Lin KC, et al. Crenolanib is a selective type I pan-FLT3 inhibitor. Proc Natl Acad Sci U S A. 2014;111:5319-5324.
  2. Tarlock K, Kylkema TA, Pollard JA, et al. Functional assessment of novel diagnostic FLT3 mutations and inhibition by kinase inhibitors. Presented at: 2017 European Hematology Association Congress; June 22-25, 2017. Abstract P184.
  3. Wang ES, Goldberg AD, Walter RB, et al. Long-term results of a phase 2 trial of crenolanib combined with 7+3 chemotherapy in adults with newly diagnosed FLT3 mutant AML. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7007.
  4. Erba H, Montesinos P, Vrhovac R, et al. Quizartinib prolonged survival vs placebo plus intensive induction and consolidation therapy followed by single-agent continuation in patients aged 18-75 years with newly diagnosed FLT3-ITD+ AML. Presented at: 2022 European Hematology Association Congress; June 9-12, 2022. Abstract S100.
  5. Stone RM, Fischer T, Paquette R, et al. Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia. Leukemia. 2012;26:2061-2068.
  6. Döhner H, Estey E, Grimwade D, et al. Long-term results of a phase 2 trial of crenolanib combined with 7+3 chemotherapy in adults with newly diagnosed FLT3 mutant AML. Blood. 2017;129:424-447.
  7. Kim K, Maiti A, Loghavi S, et al. Outcomes of TP53-mutant acute myeloid leukemia with decitabine and venetoclax. Cancer 2021;127:3772-3781.
  8. Chao MP, Takimoto CH, Feng DD, et al. Therapeutic targeting of the macrophage immune checkpoint CD47 in myeloid malignancies. Front Oncol. 2020;9:1380.
  9. Daver NG, Vyas P, Kambhampati S, et al. Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in frontline TP53m AML patients: phase 1b results. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7020.
  10. Barros MMO, Yamamoto M, Figueiredo MD, et al. Expression levels of CD47, CD35, CD55, and CD59 on red blood cells and signal-regulatory protein-α,β on monocytes from patients with warm autoimmune hemolytic anemia. Transfustion. 2008;48:154-160.
  11. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383:617-629.
  12. Daver N, Konopleva M, Maiti A, et al. Phase I/II study of azacitidine (AZA) with venetoclax (VEN) and magrolimab (Magro) in patients (pts) with newly diagnosed older/unfit or high-risk acute myeloid leukemia (AML) and relapsed/refractory (R/R) AML. Presented at: 2021 Annual Meeting of the American Society of Hemology; December 11-14, 2021. Abstract 371.
  13. Duchmann M, Micol J-B, Duployez N, et al. Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study. Blood. 2021;137:2827-2837.
  14. Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373:1136-1152.
  15. Stein EM. Molecular pathways: IDH2 mutations-co-opting cellular metabolism for malignant transformation. Clin Cancer Res. 2016;22:16-19.
  16. Middeke JM, Metzeler KH, Rollig C, et al. Differential impact of IDH1/2 mutational subclasses on outcome in adult AML: results from a large multicenter study. Blood Adv. 2022;6:1394-1405.
  17. Kotredes KP, Razmpour R, Lutton E, et al. Characterization of cancer-associated IDH2 mutations that differ in tumorigenicity, chemosensitivity and 2-hydroxyglutarate production. Oncotarget. 2019;10:2675-2692.
  18. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209-2221.
  19. Enasidenib prescribing information. Summit, NJ: Celgene Corporation; 2021.
  20. de Botton S, Risueno A, Schuh AC, et al. Overall survival by IDH2 mutant allele (R140 or R172) in patients with late-stage mutant-IDH2 relapsed or refractory acute myeloid leukemia treated with enasidenib or conventional care regimens in the phase 3 IDHENTIFY trial. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7005.
  21. de Botton S, Montesinos P, Schuh A, et al. Enasidenib vs conventional care in mutant-IDH2 relapsed/refractory acute myeloid leukemia: a randomized, phase 3 trial. Blood. 2022;Jun 17;2021014901.
  22. DiNardo C, Montesinos P, Schuh A, et al. A phase 3 study of enasidenib (ENA) versus conventional care regimens (CCR) in older patients with late-stage mutant-idh2 (mIDH2) relapsed/refractory acute myeloid leukemia (R/R AML). Presented at: 2021 European Hematology Association Congress; June 9-17, 2022. Abstract EP457.
  23. Buckley SA, Wood BL, Othus M, et al. Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis. Haematologica. 2017;102:865-873.
  24. Short NJ, Zhou S, Fu C, et al. Association of measurable residual disease with survival outcomes in patients with acute myeloid leukemia: a systematic review and meta-analysis. JAMA Oncol. 2020;6:1890-1899.
  25. Hourigan CS, Dillon LW, Gui G, et al. Pre-MEASURE: multicenter evaluation of the prognostic significance of measurable residual disease testing prior to allogeneic transplantation for adult patients with AML in first remission. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7006.
  26. Aldoss I, Forman SJ, Pullarkat V. Acute lymphoblastic leukemia in the older adult. J Oncol Pract. 2019;2:67-75.
  27. Kantarjian H, Ravandi F, Short NJ, et al. Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2018;19:240-248.
  28. Macaron W, Kantarjian HM, Short NJ, et al. Updated results from a phase II study of mini-hyper-CVD (mini-HCVD) plus inotuzumab ozogamicin (INO), with or without blinatumomab (Blina), in older adults with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (ALL). Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7011.
  29. Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367:2075-2088.
  30. Jabbour E, Short NJ, Ravandi F, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: long-term follow-up of a single-centre, phase 2 study. Lancet Haematol. 2018;5:e618-e627.
  31. Martinelli G, Boissel N, Chevallier P, et al. Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol. 2017;35:1795-1802.
  32. Foa R, Bassan R, Vitale A, et al. Dasatinib-blinatumomab for Ph-positive acute lymphoblastic leukemia in adults. N Engl J Med. 2020;383:1613-1623.
  33. Short NJ, Kantarjian HM, Konopleva M, et al. A phase II trial of a chemotherapy-free combination of ponatinib and blinatumomab in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7009.
  34. Hughes TP, Mauro MJ, Cortes JE, et al. Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failure. N Engl J Med. 2019;381:2315-2326.
  35. Réa D, Mauro MJ, Boquimpani C, et al. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood. 2021;138:2031-2041.
  36. Mauro MJ, Minami Y, Rea D, et al. Efficacy and safety results from ASCEMBL, a multicenter, open-label, phase 3 study of asciminib, a first-in-class STAMP inhibitor, vs bosutinib in patients with chronic myeloid leukemia in chronic phase after ≥2 prior tyrosine kinase inhibitors: update after 48 weeks. Presented at: 2021 Annual Meeting of the American Society of Hemology; December 11-14, 2021. Abstract 310.
  37. Réa D, Mauro MJ, Hochhaus A, et al. Efficacy and safety results from ASCEMBL, a phase 3 study of asciminib versus bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs): Week 96 update. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7004.
  38. Réa D, Hughes TP. Development of asciminib, a novel allosteric inhibitor of BCR-ABL1. Crit Rev Oncol Hematol. 2022;171:103580.
  39. Schwab U, Stein H, Gerdes J, et al. Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin’s disease and a subset of normal lymphoid cells. Nature. 1982;299:65-67.
  40. Brentuximab vedotin prescribing information. Bothell, WA: Seagen, Inc; 2022.
  41. Straus DJ, Dlogosz-Danecka M, Connors JM, et al. Brentuximab vedotin with chemotherapy for stage III or stage IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomized, phase 3 trial. Lancet Oncol. 2021:8:e410-e421.
  42. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378:331-344.
  43. Ansell SM, Radford J, Connors JM, et al. Overall survival with brentuximab vedotin in stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2022;387:310-320.
  44. Ansell SM, Connors JM, Radford JA, et al. First-line brentuximab vedotin plus chemotherapy to improve overall survival in patients with stage III/IV classical Hodgkin lymphoma: an updated analysis of ECHELON-1. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7503.
  45. Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomized, phase 3 non-inferiority trial. Lancet. 2013;381:1203-1210.
  46. Flinn IW, van der Jagt R, Kahl B, et al. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019;37:984-991.
  47. Ibrutinib prescribing information. San Francisco, CA: Pharmacyclics LLC; Horsham, PA: Janssen Biotech, Inc; 2022.
  48. Maddocks K, Christian B, Jaglowski S, et al. A phase 1/1b study of rituximab, bendamustine, and ibrutinib in patients with untreated and relapsed/refractory non-Hodgkin lymphoma. Blood. 2015;125:242-248.
  49. Wang M, Jurczak W, Jerkeman M, et al. Primary results from the double-blind, placebo-controlled, phase III SHINE study of ibrtutinb in combination with bendamustine-rituximab (BR) and R maintenance as a first-line treatment for older patients with mantle cell lymphoma (MCL). Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7502.
  50. Wang M, Jurczak W, Jerkeman M, et al. Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma. N Engl J Med. 2022;386:2482-2494.
  51. Hutchings M, Morschhauser F, Iacoboni G, et al. Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial. J Clin Oncol. 2021;39:1959-1970.
  52. Bacac M, Colombetti S, Herter S, et al. CD20-TCB with obinutuzumab pretreatment as next-generation treatment of hematologic malignancies. Clin Cancer Res. 2018;24:4785-4797.
  53. Dickinson M, Carlo-Stella C, Morschhauser F, et al. Glofitamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and ≥ 2 prior therapies: pivotal phase II expansion results. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7500.
  54. Gopal AK, Schuster SJ, Fowler NH, et al. Ibrutinib as treatment for patients with relapsed/refractory follicular lymphoma: results from the open-label, multicenter, phase II DAWN study. J Clin Oncol. 2018;36:2405-2412.
  55. Tam CS, Quach H, Nicol A, et al. Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma. Blood Adv. 2020;4:4802-4811.
  56. Zinzani PL, Mayer J, Auer R, et al. Zanubrutinib plus obinutuzumab (ZO) vs obinutuzumab (O) monotherapy in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL): primary analysis of the phase 2 randomized ROSEWOOD trial. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7510.
  57. Tam CS, Opat S, D’Sa S, et al. A randomized phase 3 trial of zanubrtuinib vs ibrutinib in symptompatic Waldenström macroglobulinemia: the ASPEN study. Blood. 2020;136:2038-2050.
  58. Leonard JP, Trneny M, Izutsu K, et al. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019;37:1188-1199.
  59. Acalabrutinib prescribing information. Wilmington, DE: AstraZeneca; 2019.
  60. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE-TN): a randomized, controlled, phase 3 trial. Lancet. 2020;395:1278-1291.
  61. Sharman JP, Egyed M, Jurczak J, et al. Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: five-year follow-up of ELEVATE-TN. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7539.
  62. Sharman JP, Egyed M, Jurczak J, et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naïve chronic lymphocytic leukemia. Leukemia. 2022;36:1171-1175.
  63. Wierda WG, Barr PM, Siddiqi T, et al. Fixed-duration (FD) ibrutinib (I) + venetoclax (V) for first-line (1L) treatment (tx) of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLLS): three-year follow-up from the FD cohort of the phase 2 CAPTIVATE study. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7519.
  64. Venetoclax prescribing information. San Francisco, CA: Genentech, Inc; 2022.
  65. Tam CS, Allan JN, Siddiqi T, et al. Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort. Blood. 2022;139:3278-3289.
  66. Ghia P, Pluta A, Wach M, et al. ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2020;38:2849-2861.
  67. Jurczak W, Pluta A, Wach M, et al. Acalabrutinib versus rituximab plus idelalisib or bendamustine in relapsed/refractory chronic lymphocytic leukemia: ASCEND results at 4 years of follow-up. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 7538.
  68. Perrot A, Lauwers-Cances V, Cazaubiel T, et al: Early versus late autologous stem cell transplant in newly diagnosed multiple myeloma: long-term follow-up analysis of the IFM 2009 trial. Presented at: 2020 Annual Meeting of the American Society of Hematology; December 5-8, 2020. Abstract 143.
  69. Richardson PG, Jacobus SJ, Weller E, et al. Lenalidomide, bortezomib, and dexamethasone (RVd) ± autologous stem cell transplantation (ASCT) and R maintenance to progression for newly diagnosed multiple myeloma (NDMM): the phase 3 DETERMINATION trial. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract LBA4.
  70. Richardson PG, Jacobus SJ, Weller EA. Triplet therapy, transplantation, and maintenance until progression in myeloma. N Engl J Med. 2022;387:132-147.
  71. Attal M, Lauwers-Cances L, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376:1311-1320.
  72. McCarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35:3279-3289.
  73. Jasielec JK, Kubicki T, Raje N, et al. Carfilzomib, lenalidomide, and dexamethasone plus transplant in newly diagnosed multiple myeloma. Blood. 2020;126:2513-2523.
  74. Gay F, Musto P, Rota-Scalabrini D, et al. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial. Lancet Oncol. 2021;22:1705-1720.
  75. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: multiple myeloma. v.5.2022. nccn.org. Accessed September 1, 2022.
  76. Dytfeld D, Wrobel T, Jamroziak K, et al. ATLAS: a phase 3 randomized trial of carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone after stem-cell transplant for multiple myeloma. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 8001.
  77. Mateos M-V, WeiselK, De Stefano V, et al. LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed/refractory multiple myeloma (RRMM) receiving ≥3 prior lines of therapy. Presented at: 2021 Annual Meeting of the American Society of Clinical Oncology; June 4-8, 2021. Abstract 8041.
  78. Delforge M, Moreau P, Einsele H, et al. Health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma (RRMM) receiving real-life current standard of care (SOC) in the LocoMMotion study. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 8030.
  79. Costa LJ, Lin Y, Martin TG, et al. Cilta-cel versus conventional treatment in patients with relapse/refractory multiple myeloma. Presented at: 2021 Annual Meeting of the American Society of Clinical Oncology; June 4-8, 2021. Abstract 8030.
  80. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387:495-505.
  81. Usmani SZ, Garfall AL, van de Donk NWCJ, et al. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet. 2021;398:665-674.
  82. Nooka AJ, Moreau P, Usmani AZ, et al. Teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): updated efficacy and safety results from MajesTEC-1. Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 8007.
  83. Tai Y-T, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015;7:1187-1199.
  84. Boucher K, Parquet N, Widen R, et al. Stemness of B-cell progenitors in multiple myeloma bone marrow. Clin Cancer Res. 2012;18:6155-6158.
  85. Nerreter T, Letschert S, Gotz R, et al. Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T. Nat Commun. 2019;10:3137.
  86. Munshi NC, Anderson LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384:705-716.
  87. Martin T, Usmani SZ, Schecter JM, et al. Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma. Curr Med Res Opin. 2021;37:1779-1788.
  88. Zhang M, Hu Y, Ding X, et al. Phase I open-label single arm study of GPRC5D CAR T-cells (OriCAR-017) in patients with relapsed/refractory multiple myeloma (POLARIS). Presented at: 2022 European Hematology Association Congress; June 9-12, 2022. Abstract S263.
  89. Huang H, Hu Y, Zhang M, et al. Phase I open-label single arm study of GPRC5D CAR T-cells (OriCAR-017) in patients with relapsed/refractory multiple myeloma (POLARIS). Presented at: 2022 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2022. Abstract 8004.