TY - JOUR
TI - A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: The ASPEN study
AU - Tam, C.S.
AU - Opat, S.
AU - D'Sa, S.
AU - Jurczak, W.
AU - Lee, H.-P.
AU - Cull, G.
AU - Owen, R.G.
AU - Marlton, P.
AU - Ewahlin, B.
AU - Sanz, R.G.
AU - McCarthy, H.
AU - Mulligan, S.
AU - Tedeschi, A.
AU - Castillo, J.J.
AU - Czyz, J.
AU - De Larrea, C.F.
AU - Belada, D.
AU - Libby, E.
AU - Matous, J.V.
AU - Motta, M.
AU - Siddiqi, T.
AU - Tani, M.
AU - Trneny, M.
AU - Minnema, M.C.
AU - Buske, C.
AU - Leblond, V.
AU - Trotman, J.
AU - Chan, W.Y.
AU - Schneider, J.
AU - Ro, S.
AU - Cohen, A.
AU - Huang, J.
JO - Blood advances
PY - 2020
VL - 136
TODO - 18
SP - 2038-2050
PB - American Society of Hematology
SN - null
TODO - 10.1182/BLOOD.2020006844
TODO - beta 2 microglobulin;  chemokine receptor CXCR4;  hemoglobin;  ibrutinib;  immunoglobulin A;  immunoglobulin G;  immunoglobulin M;  myeloid differentiation factor 88;  zanubrutinib;  adenine;  antineoplastic agent;  ibrutinib;  piperidine derivative;  pyrazole derivative;  pyrimidine derivative;  zanubrutinib, adverse drug reaction;  aged;  anemia;  arthralgia;  Article;  atrial fibrillation;  backache;  bacteremia;  blood viscosity;  bone marrow biopsy;  cancer chemotherapy;  cohort analysis;  comorbidity;  comparative effectiveness;  computer assisted tomography;  constipation;  contrast enhancement;  controlled study;  contusion;  diarrhea;  drug induced disease;  drug safety;  dyspnea;  European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30;  fatigue;  female;  fever;  headache;  heart arrest;  heart infarction;  hematuria;  hemoglobin blood level;  hemoglobin determination;  hepatitis;  high throughput sequencing;  human;  hypertension;  immunoglobulin A multiple myeloma;  interstitial lung disease;  liver injury;  major clinical study;  male;  Mantel Haenszel test;  missense mutation;  multiple myeloma;  muscle spasm;  nausea;  neutropenia;  nuclear magnetic resonance imaging;  open study;  overall survival;  patient-reported outcome;  peripheral edema;  peripheral neuropathy;  phase 3 clinical trial;  pneumonia;  priority journal;  progression free survival;  quality of life;  quantitative analysis;  randomized controlled trial;  rash;  sepsis;  skin cancer;  subdural hematoma;  thrombocytopenia;  treatment duration;  treatment interruption;  treatment response;  tumor lysis syndrome;  tumor volume;  upper respiratory tract infection;  urinary tract infection;  vomiting;  Waldenstroem macroglobulinemia;  adult;  clinical trial;  follow up;  middle aged;  multicenter study;  pathology;  prognosis;  survival rate;  very elderly;  Waldenstroem macroglobulinemia, Adenine;  Adult;  Aged;  Aged, 80 and over;  Antineoplastic Combined Chemotherapy Protocols;  Cohort Studies;  Female;  Follow-Up Studies;  Humans;  Male;  Middle Aged;  Piperidines;  Prognosis;  Pyrazoles;  Pyrimidines;  Survival Rate;  Waldenstrom Macroglobulinemia
TODO - Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ‡1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P 5 .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ‡3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity. © 2020 American Society of Hematology. All rights reserved.
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