BTKis for CLL: Module

CME

BTK Inhibitor Therapy for Patients With CLL: A Global Perspective

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit

Released: March 13, 2023

Expiration: March 12, 2024

Toby A Eyre
Toby A Eyre, MBChB, MD

Activity

Progress
1
Course Completed
References

  1. Young RM, Staudt LM. Targeting pathological B cell receptor signalling in lymphoid malignancies. Nat Rev Drug Discov. 2013;12:229-243.
  2. Acalabrutinib [summary of product characteristics]. Södertälje, Sweden: AstraZeneca AB; 2021.
  3. Ibrutinib [summary of product characteristics]. Beerse, Belgium: Janssen-Cilag International NV; 2022.
  4. Zanubrutinib [summary of product characteristics]. Dublin, Ireland: BeiGene Ireland Limited; 2022.
  5. Acalabrutinib [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022.
  6. Ibrutinib [prescribing information]. San Francisco, CA: Pharmacyclics LLC; Horsham, PA: Janssen Biotech, Inc; 2022.
  7. Zanubrutinib [prescribing information]. San Mateo, CA: BeiGene USA, Inc.; 2022.
  8. 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.
  9. Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2022;[Epub ahead of print].
  10. Mato AR, Woyach JA, Brown JR, et al. Efficacy of pirtobrutinib in covalent BTK-inhibitor pre-treated relapsed / refractory CLL/SLL: additional patients and extended follow-up from the phase 1/2 BRUIN study. Presented at: 2022 American Society of Hematology Annual Meeting; December 10-13, 2022. Abstract 961.
  11. Woyach JA, Flinn IW, Awan FT, et al. Efficacy and safety of nemtabrutinib, a wild-type and C481S-mutated Bruton tyrosine kinase inhibitor for B-cell malignancies: updated analysis of the open-label phase 1/2 dose-expansion Bellwave-001 study. Presented at: 2022 American Society of Hematology Annual Meeting; December 10-13, 2022. Abstract 3114.
  12. Kaptein A, de Bruin G, Emmelot-van Hoek M, et al. Potency and selectivity of BTK inhibitors in clinical development for B-cell malignancies. Presented at: 2018 American Society of Hematology Annual Meeting; December 1-4, 2018. Abstract 1871.
  13. Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32:23-33.
  14. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: chronic lymphocytic leukemia/small lymphocytic lymphoma. v.1.2023. nccn.org. Accessed January 2, 2023.
  15. Barr PM, Owen C, Robak T, et al. Up to 8 years follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;[Epub ahead of print].
  16. Hillmen P, Pitchford A, Bloor A, et al. Ibrutinib plus rituximab is superior to FCR in previously untreated CLL: results of the phase III NCRI FLAIR trial. Presented at: 2021 American Society of Hematology Annual Meeting; December 11-14, 2021. Abstract 642.
  17. Moreno C, Greil R, Demirkan F, et al. First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase III iLLUMINATE trial. Haematologica. 2022;107:2108-2120.
  18. Shanafelt TD, Xang XV, Hanson CA, et al. Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial. Blood. 2022;140:112-120.
  19. Woyach JA, Ruppert AS, Heerema NA, et al. Long-term results of Alliance A041202 show continued advantage of ibrutinib-based regimens compared with bendamustine plus rituximab (BR) chemoimmunotherapy. Presented at: 2021 American Society of Hematology Annual Meeting; December 11-14, 2021. Abstract 639.
  20. 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.
  21. Al-Sawaf O, Zhang C, Robrecht S, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 4-year follow-up analysis of the randomized CLL14 study. Presented at: European Hematology Association Congress; June 9-17, 2021. Abstract S146.
  22. 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.
  23. Sharma S, Pepin X, Burri H, et al. New acalabrutinib formulation enables co-administration with proton pump inhibitors and dosing in patients unable to swallow capsules (ELEVATE-PLUS). Presented at: 2021 American Society of Hematology Annual Meeting; December 11-14, 2021. Abstract 4365.
  24. Aarup K, Rotbain EC, Enggaard L, et al. Real-world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib. Eur J Haematol. 2020;105:646-654.
  25. Mato AR, Nabhan C, Thompson MC, et al. Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis. Haematologica. 2018;103:874-879.
  26. Woyach JA, Ruppert AS, Guinn D, et al. BTKC481S-mediated resistance to ibrutinib in chronic lymphocytic leukemia. J Clin Oncol. 2017;35:1437-1443.
  27. Mato AR, Hess LM, Chen Y, et al. Outcomes for patients with chronic lymphocytic leukemia (CLL) previously treated with both a covalent BTK and BCL2 inhibitor in the United States: a real-world database study. Clin Lymphoma Myeloma Leuk. 2023;23:57-67.
  28. Rogers KA, Thompson PA, Allan JN, et al. Phase II study of acalabrutinib in ibrutinib-intolerant patients with relapsed/refractory chronic lymphocytic leukemia. Haematologica. 2021;106:2364-2373.
  29. Shadman M, Sharman JP, Levy MY, et al. Phase 2 study of zanubrutinib in patients with relapsed/refractory B-cell malignancies intolerant to ibrutinib/acalabrutinib. Presented at: 2020 American Society of Hematology Annual Meeting; December 5-8, 2020. Abstract 2947.
  30. Byrd JC, Hillmen P, Ghia P, et al. Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial. J Clin Oncol. 2021;39:3441-3452.
  31. Bhat SA, Gambril J, Azali L, et al. Ventricular arrhythmias and sudden death events following acalabrutinib initiation. Blood. 2022;140:2142-2145.
  32. Lipsky A, Lamanna N. Managing toxicities of Bruton tyrosine kinase inhibitors. Hematology Am Soc Hematol Educ Program. 2020;2020:336-345.
  33. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381:432-443.
  34. O’Brien S, Hillmen P, Coutre S, et al. Safety analysis of four randomized controlled studies of ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma or mantle cell lymphoma. Clin Lymphoma Myeloma Leuk. 2018;18:648-657.
  35. Wang E, Mi X, Thompson MC, et al. Mechanisms of resistance to noncovalent Bruton's tyrosine kinase inhibitors. N Engl J Med. 2022;386:735-743.