Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma
Tóm tắt
Zanubrutinib, a highly selective Bruton tyrosine kinase inhibitor, was evaluated in a phase 1/2 study in patients with various B-cell malignancies. In the subgroup of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), zanubrutinib was administered as 160 mg twice daily (n = 14), 320 mg once daily (n = 18), or ≤160 mg total dose (n = 5). Herein, we report results for patients receiving a total daily dose of 320 mg (N = 32). Median study follow-up was 18.8 months. Eighteen patients discontinued treatment, 10 because of progressive disease and 8 because of adverse events (AEs); 1 AE (peripheral edema) was considered to be related to zanubrutinib treatment. The most common AEs were diarrhea (43.8%), contusion (37.5%), constipation (31.3%), and upper respiratory tract infection (31.3%). Infection was the most commonly reported AE of interest (18.8% of patients experienced grade ≥3 infection). At least 1 AE of grade ≥3 was reported in 59.4% of patients; grade ≥3 AEs that were reported in >2 patients were anemia (12.5%), pneumonia (9.4%), and myalgia (9.4%). Overall response rate was 84%, with 25% achieving a complete response. Median duration of response was 18.5 months. Median progression-free survival (PFS) was 21.1 months. Zanubrutinib was well tolerated and demonstrated activity in patients with R/R MCL. The trial is registered at www.clinicaltrials.gov as #NCT02343120.
Từ khóa
Tài liệu tham khảo
Cortelazzo, 2020, Mantle cell lymphoma, Crit Rev Oncol Hematol., 153, 103038, 10.1016/j.critrevonc.2020.103038
Smith, 2018, Impact of novel therapies for mantle cell lymphoma in the real world setting: a report from the UK’s Haematological Malignancy Research Network (HMRN), Br J Haematol., 181, 215, 10.1111/bjh.15170
Kahl, 2019, Recent advances and future directions in mantle cell lymphoma research: report of the 2018 mantle cell lymphoma consortium workshop, Leuk Lymphoma., 60, 1853, 10.1080/10428194.2019.1571205
Velders, 1996, Mantle-cell lymphoma: a population-based clinical study, J Clin Oncol., 14, 1269, 10.1200/JCO.1996.14.4.1269
Kumar, 2019, Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse, Blood Cancer J., 9, 50, 10.1038/s41408-019-0209-5
Cohen, 2015, Role of allogeneic stem cell transplantation in mantle cell lymphoma, Eur J Haematol., 94, 290, 10.1111/ejh.12442
Wang, 2020, KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma, N Engl J Med., 382, 1331, 10.1056/NEJMoa1914347
Cinar, 2013, Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by Ibrutinib induces apoptosis, Leuk Res., 37, 1271, 10.1016/j.leukres.2013.07.028
Fowler, 2013, Targeting B-cell receptor signaling: changing the paradigm, Hematology (Am Soc Hematol Educ Program)., 2013, 553, 10.1182/asheducation-2013.1.553
2020
2019
2019
Rule, 2019, Ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma: extended 3.5-year follow up from a pooled analysis, Haematologica., 104, e211, 10.3324/haematol.2018.205229
Wang, 2018, Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial, Lancet., 391, 659, 10.1016/S0140-6736(17)33108-2
Tam, 2019, Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL, Blood., 134, 851, 10.1182/blood.2019001160
Advani, 2013, Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies, J Clin Oncol., 31, 88, 10.1200/JCO.2012.42.7906
Tam, 2015, The BTK inhibitor, Bgb-3111, is safe, tolerable, and highly active in patients with relapsed/refractory B-cell malignancies: initial report of a phase 1 first-in-human trial, Blood., 126, 832, 10.1182/blood.V126.23.832.832
Tam, 2018, A head-to-head phase III study comparing zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia, Future Oncol., 14, 2229, 10.2217/fon-2018-0163
Tam, 2016, Twice daily dosing with the highly specific BTK inhibitor, Bgb-3111, achieves complete and continuous BTK occupancy in lymph nodes, and is associated with durable responses in patients (pts) with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Blood., 128, 642, 10.1182/blood.V128.22.642.642
Tam, 2019, Pooled analysis of safety data from monotherapy studies of the Bruton tyrosine kinase (BTK) inhibitor, zanubrutinib (BGB-3111) in B-cell malignancies, HemaSphere., 3, 526, 10.1097/01.HS9.0000562920.26603.5b
Trotman, 2017, Bruton’s tyrosine kinase (BTK) inhibitor BGB-3111 demonstrates high very good partial response (VGPR) rate in patients with Waldenström macroglobulinemia (WM), Hematol Oncol., 35, 59, 10.1002/hon.2437_58
Cheson, 2014, Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification, J Clin Oncol., 32, 3059, 10.1200/JCO.2013.54.8800
Clopper, 1934, The use of confidence or fiducial limits illustrated in the case of the binomial, Biometrika., 26, 404, 10.1093/biomet/26.4.404
Brookmeyer, 1982, A confidence interval for the median survival time, Biometrics., 38, 29, 10.2307/2530286
Goy, 2009, Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study, Ann Oncol., 20, 520, 10.1093/annonc/mdn656
Trněný, 2016, Lenalidomide versus investigator’s choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial, Lancet Oncol., 17, 319, 10.1016/S1470-2045(15)00559-8
Hock, 2016, Incidence of cutaneous squamous cell carcinoma in a New Zealand population of chronic lymphocytic leukaemia patients, Intern Med J., 46, 1414, 10.1111/imj.13261
Royle, 2011, Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study, Br J Cancer., 105, 1076, 10.1038/bjc.2011.313
Tam, 2020, ASPEN: Results of a phase III randomized trial of zanubrutinib versus ibrutinib for patients with Waldenström macroglobulinemia (WM), J Clin Oncol., 38, 8007, 10.1200/JCO.2020.38.15_suppl.8007