ASH 2022: Lymphomas and CLL

CME

Key Studies in Lymphomas and CLL: Independent Conference Coverage of ASH 2022

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit

Released: April 17, 2023

Expiration: April 16, 2024

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References

  1. Dreyling M, Doorduijn JK, Gine E, et al. Efficacy and safety of ibrutinib combined with standard first-line treatment or as substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma: results from the randomized triangle trial by the European MCL Network. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 1.
  2. Ibrutinib [prescribing information]. South San Francisco, CA: Pharmacyclics LLC; 2022. 
  3. Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369:507-516.
  4. Davids MS, Brown JR. Ibrutinib: a first in class covalent inhibitor of Bruton’s tyrosine kinase. Future Oncol. 2014;10:957-967.
  5. Dreyling M, Lenz G, Hoster E, et al. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005;105:2677-2684. 
  6. Hermine O, Hoster E, Walewski J, et al; European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016;388:565-575.
  7. Hermine O, Jiang L, Walewski J, et al; European Mantle Cell Lymphoma Network. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: long-term follow-up of the randomized Mantle Cell Lymphoma Younger trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023;41:479-484.
  8. Le Gouill S, Thieblemont C, Oberic L, et al; LYSA Group. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377:1250-1260. 
  9. Wang M, Jurczak W, Jerkeman M, et al. Primary results from the double-blind, placebo-controlled, phase III SHINE study of ibrutinib 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 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022. Abstract LBA7502. 
  10. Ruan J, Martin P, Shah B, et al. Lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma. N Engl J Med. 2015;373:1835-1844. 
  11. Ruan J, Martin P, Christos P, et al. Five-year follow-up of lenalidomide plus rituximab as initial treatment of mantle cell lymphoma. Blood. 2018;132:2016-2025.
  12. Ruan J, Leonard JP, Chen GZ et al. Phase 2 trial of acalabrutinib-lenalidomide-rituximab (ALR) with real-time monitoring of MRD in patients with treatment-naïve mantle cell lymphoma. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 73.
  13. Ujjani CS, Jung S-H, Pitcher B, et al. Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103. Blood. 2016;128:2510.
  14. Falchi L, Vardhana SA, Salles GA. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities. Blood. 2023;141:467-480.
  15. Mosunetuzumab [prescribing information]. South San Francisco, CA: Genentech, Inc; 2022. 
  16. Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23:1055-1065.
  17. Bannerji R, Arnason JE, Advani RH, et al. Odronextamab, a human CD20xCD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Lancet Haematol. 2022;9:e327-e339.
  18. Kim TM, Taszner M, Cho SG, et al. Odronextamab in patients with relapsed/refractory (R/R) follicular lymphoma (FL) grade 1–3a: results from a prespecified analysis of the pivotal phase II study ELM-2. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 949
  19. Falchi L, Abrisqueta P, Nijland M, et al. Subcutaneous epcoritamab with rituximab + lenalidomide in patients with relapsed or refractory follicular lymphoma: phase 1/2 trial update. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 609.
  20. Falchi L, Leslie LA, Belada D, et al. Subcutaneous epcoritamab in combination with rituximab + lenalidomide (R2) for first-line treatment of follicular lymphoma: initial results from phase 1/2 trial. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 611.
  21. NCCN 360. Epcoritamab accepted for priority review by FDA in treatment of LBCL. jnccn360.org/b-cell-lymphomas/news/epcoritamab-accepted-for-priority-review-by-fda-in-treatment-of-lbcl. Accessed March 15, 2023.
  22. Thieblemont C, Phillips T, Ghesquieres H, et al. Subcutaneous epcoritamab in patients with relapsed or refractory large B-cell lymphoma (EPCORE NHL-1): pivotal results from a phase 2 study. Presented at: 2022 Congress of the European Hematology Association; June 9-12, 2022. Abstract LB2364. 
  23. Lenalidomide [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co; 2022. 
  24. Engelberts PJ, Hiemstra IH, de Jong B, et al. DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine. 2020;52:102625.
  25. Chiu, CW, Hiemstra IH, Hagen, WT, et al. Preclinical evaluation of epcoritamab combined with standard of care therapies for the treatment of B-cell lymphomas. Presented at: 2021 American Association for Cancer Research Annual Meeting; April 10-15, 2021. Abstract 1574.
  26. Yuan H, Nishikori M, Otsuka Y, et al. The EZH2 inhibitor tazemetostat upregulates the expression of CCL17/TARC in B-cell lymphoma and enhances T-cell recruitment. Cancer Sci. 2021;112:4604-4616. 
  27. Béguelin W, Teater M, Meydan C, et al. Mutant EZH2 induces pre-malignant lymphoma niche by reprogramming the immune response. Cancer Cell. 2020;37:655-673. 
  28. Batlevi CL, Salles G, Park SI, et al. Tazemetostat in combination with lenalidomide and rituximab in patients with relapsed/refractory follicular lymphoma: phase 1b results of Symphony-1. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 954.
  29. Tazemetostat [prescribing information]. Cambridge, MA: Epizyme, Inc; 2020.
  30. Ferreri AJ, Cwynarski K, Pulczynski E, et al; International Extranodal Lymphoma Study Group (IELSG). Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016;3:e217-27. 
  31. Ferreri AJM, Cwynarski K, Pulczynski E, et al; IELSG32 study investigators. Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial. Leukemia. 2022;36:1870-1878.
  32. Illerhaus G, Marks R, Ihorst G, et al. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006;24:3865-3870. 
  33. Illerhaus G, Ferreri AJM, Binder M, et al. Effects on survival of non-myeloablative chemoimmunotherapy compared to high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) as consolidation therapy in patients with primary CNS lymphoma - results of an international randomized phase III trial (MATRix/IELSG43). Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract LBA-3.
  34. Batchelor T, Giri S, Ruppert AS, et al. Myeloablative versus non-myeloablative consolidative chemotherapy for newly diagnosed primary central nervous system lymphoma: results of CALGB 51101 (Alliance). J Clin Oncol. 2021;39:(suppl 15):7506-7506. 
  35. Kostakoglu l, Martelli M, Sehn LH, et al. End-of-treatment PET/CT predicts PFS and OS in DLBCL after first-line treatment: results from GOYA. Blood Adv. 2021;5:1283-1290.
  36. Roschewski M, Dunleavy K, Pittaluga S, et al. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Lancet Oncol. 2015;16:541-549.
  37. Kurtz DM, Soo J, Co Ting Keh L, et al. Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA. Nat Biotechnol. 2021;39:1537-1547. 
  38. Roschewski M, Kurtz DM, Westin J, et al. MRD-negativity as a potential surrogate endpoint after frontline DLBCL Therapy: pooled analysis of trials & implications for clinical trial design. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 322.
  39. Kim WS, Kim TM, Cho SG, et al.  Odronextamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): results from a prespecified analysis of the pivotal phase II study ELM-2. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 444
  40. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387:2220-2231. 
  41. JNCCN 360. Priority review granted by the FDA for glofitamab in treatment of large B-cell lymphoma. jnccn360.org/b-cell-lymphomas/news/priority-review-granted-by-the-fda-for-glofitamab-in-treatment-of-large-b-cell-lymphoma. Accessed March 15, 2023.
  42. Connors JM, Jurczak W, Straus DJ, et al; ECHELON-1 Study Group. 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; ECHELON-1 Study Group. Overall survival with brentuximab vedotin in stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2022;387:310-320. 
  44. Flinn IW, Friedman J, Ho L, et al. Brentuximab vedotin in combination with nivolumab, doxorubicin, and dacarbazine in newly diagnosed patients with advanced stage Hodgkin lymphoma (SGN35-027, Trial in Progress). Blood. 2021;138:1369.
  45. Lee H, Flinn IW, Melear J, et al. Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) for advanced stage classic Hodgkin lymphoma: updated efficacy and safety results from the single-arm phase 2 study (SGN35-027 Part B). Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 314.
  46. Stuver R, Michaud L, Casulo C, et al. Brentuximab vedotin combined with chemotherapy in newly diagnosed, early-stage, unfavorable-risk Hodgkin lymphoma: extended follow-up with evaluation of baseline metabolic tumor volume and PET2. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 730.
  47. Tam CS, Ou YC, Trotman J, et al. Clinical pharmacology and PK/PD translation of the second-generation Bruton’s tyrosine kinase inhibitor, zanubrutinib. Expert Rev Clin Pharmacol. 2021;14:1329-1344.
  48. Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23:1031-1043.
  49. Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib demonstrates superior progression-free survival (PFS) compared with ibrutinib for treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL): results from final analysis of ALPINE randomized phase 3 study. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract LBA-6.
  50. Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2023.388:319-332.
  51. Hillmen P, Eichhorst B, Brown JR, et al. First interim analysis of ALPINE study: results of a phase 3 randomized study of zanubrutinib vs ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Presented at: 2021 Congress of the European Hematology Association; June 9-17, 2021. Abstract LB1900.
  52. Allan JN, Siddiqi T, Kipps TJ, et al. Treatment outcomes after undetectable MRD with first-line ibrutinib (Ibr) plus venetoclax (Ven): fixed duration treatment (placebo) versus continued Ibr with up to 5 years median follow-up in the CAPTIVATE Study. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 92.
  53. Wierda WG, Allan JN, Siddiqi T, et al. Ibrutinib plus venetoclax for first-line treatment of chronic lymphocytic leukemia: primary analysis results from the minimal residual disease cohort of the randomized phase II CAPTIVATE study. J Clin Oncol. 2021;39:3853-3865. 
  54. Ghia P, Allan JN, Siddiqi T, et al. First-line treatment with ibrutinib (Ibr) plus venetoclax (Ven) for chronic lymphocytic leukemia (CLL): 2-year post-randomization disease-free survival (DFS) results from the minimal residual disease (MRD) cohort of the phase 2 CAPTIVATE study. Presented at: 2021 American Society of Hematology Annual Meeting and Exposition; December 10-14, 2021. Abstract 68.
  55. Kater AP, Owen C, Moreno C, et al. Fixed-duration ibrutinib-venetoclax in patients with chronic lymphocytic leukemia and comorbidities. N Engl J Med. 2022:1.
  56. Sharman JP, Egyed M, Jurczak W, 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. 
  57. Rogers KA, Huang Y, Ruppert AS, et al. Phase II study of combination obinutuzumab, ibrutinib, and venetoclax in treatment-naive and relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2020;38:3626-3637. 
  58. Soumerai JD, Mato AR, Dogan A, et al. Zanubrutinib, obinutuzumab, and venetoclax with minimal residual disease-driven discontinuation in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2021;8:e879-e890.
  59. Huber H, Edenhofer S, von Tresckow J, et al. Obinutuzumab (GA-101), ibrutinib, and venetoclax (GIVe) frontline treatment for high-risk chronic lymphocytic leukemia. Blood. 2022;139:1318-1329. 
  60. Ryan CE, Lampson BL, Tyekucheva S, et al. Updated results from a multicenter, phase 2 study of acalabrutinib, venetoclax, obinutuzumab (AVO) in a population of previously untreated patients with CLL enriched for high-risk disease. Presented at: 2022 American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022. Abstract 344
  61. Davids MS, Lampson BL, Tyekucheva S, et al. Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. Lancet Oncol. 2021;22:1391-1402. 
  62. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131:2745-2760.