Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F20%3A10419379" target="_blank" >RIV/00216208:11110/20:10419379 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/20:10419379

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=p.B4QYUOXG" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=p.B4QYUOXG</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1182/bloodadvances.2020003010" target="_blank" >10.1182/bloodadvances.2020003010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial

Popis výsledku v původním jazyce

Patients with Waldenstrom macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88(WT)) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study. Zanubrutinib is a novel, selective Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target activity. The ASPEN study consisted of a randomized comparison of zanubrutinib and ibrutinib efficacy and safety in patients withWMwho have the MYD88 mutation, as well as a separate cohort of patients without MYD88 mutation (MYD88(WT)) or with unknown mutational status who received zanubrutinib. Results from the latter single-arm cohort are reported herein. Efficacy endpoints included overall, major and complete (CR) or very good partial response (VGPR) rates, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Twenty-eight patients (23 relapsed/refractory; 5 treatment-naive) were enrolled, including 26 with centrally confirmed MYD88(WT) disease and 2 with unknown MYD88 mutational status. At a median follow-up of 17.9 months, 7 of 26 MYD88(WT) patients (27%) had achieved a VGPR and 50% a major response (partial response or better); there were no CRs. At 18 months, the estimated PFS and OS rates were 68% and 88%, respectively, while the median DOR had not been reached. Two patients discontinued zanubrutinib due to adverse events. Treatment-emergent hypertension, atrial fibrillation, and major hemorrhages were reported in 3, 1 and 2 patients (including 1 concurrent with enoxaparin therapy), respectively. Results of this substudy demonstrate that zanubrutinib monotherapy can induce high quality responses in patients with MYD88(WT) WM. This trial is registered on www.clinicaltrials.gov as NCT #03053440.

Název v anglickém jazyce

Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial

Popis výsledku anglicky

Patients with Waldenstrom macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88(WT)) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study. Zanubrutinib is a novel, selective Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target activity. The ASPEN study consisted of a randomized comparison of zanubrutinib and ibrutinib efficacy and safety in patients withWMwho have the MYD88 mutation, as well as a separate cohort of patients without MYD88 mutation (MYD88(WT)) or with unknown mutational status who received zanubrutinib. Results from the latter single-arm cohort are reported herein. Efficacy endpoints included overall, major and complete (CR) or very good partial response (VGPR) rates, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Twenty-eight patients (23 relapsed/refractory; 5 treatment-naive) were enrolled, including 26 with centrally confirmed MYD88(WT) disease and 2 with unknown MYD88 mutational status. At a median follow-up of 17.9 months, 7 of 26 MYD88(WT) patients (27%) had achieved a VGPR and 50% a major response (partial response or better); there were no CRs. At 18 months, the estimated PFS and OS rates were 68% and 88%, respectively, while the median DOR had not been reached. Two patients discontinued zanubrutinib due to adverse events. Treatment-emergent hypertension, atrial fibrillation, and major hemorrhages were reported in 3, 1 and 2 patients (including 1 concurrent with enoxaparin therapy), respectively. Results of this substudy demonstrate that zanubrutinib monotherapy can induce high quality responses in patients with MYD88(WT) WM. This trial is registered on www.clinicaltrials.gov as NCT #03053440.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Blood Advances

ISSN

2473-9529

e-ISSN

—

Svazek periodika

4

Číslo periodika v rámci svazku

23

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

6009-6018

Kód UT WoS článku

000596950900014

EID výsledku v databázi Scopus

2-s2.0-85098063221