PMID- 37478390 OWN - NLM STAT- MEDLINE DCOM- 20231117 LR - 20231125 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 41 IP - 33 DP - 2023 Nov 20 TI - Zanubrutinib Versus Ibrutinib in Symptomatic Waldenstrom Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study. PG - 5099-5106 LID - 10.1200/JCO.22.02830 [doi] AB - The phase III ASPEN study demonstrated the comparable efficacy and improved safety of zanubrutinib versus ibrutinib in patients with Waldenstrom macroglobulinemia (WM). Here, we report long-term follow-up outcomes from ASPEN. The primary end point was the sum of very good partial response (VGPR) + complete response (CR) rates; secondary and exploratory end points were also reported. Cohort 1 comprised 201 patients (myeloid differentiation primary response 88-mutant WM: 102 receiving zanubrutinib; 99 receiving ibrutinib); cohort 2 comprised 28 patients (myeloid differentiation primary response 88 wild-type WM: 28 zanubrutinib; 26 efficacy evaluable). At 44.4-month median follow-up, VGPR + CR rates were 36.3% with zanubrutinib versus 25.3% with ibrutinib in cohort 1 and 30.8% with one CR in cohort 2. In patients with CXC motif chemokine receptor 4 mutation, VGPR + CR rates were 21.2% with zanubrutinib versus 10.0% with ibrutinib (cohort 1). Median progression-free survival and overall survival were not reached. Any-grade adverse events (AEs) of diarrhea (34.7% v 22.8%), muscle spasms (28.6% v 11.9%), hypertension (25.5% v 14.9%), atrial fibrillation/flutter (23.5% v 7.9%), and pneumonia (18.4% v 5.0%) were more common with ibrutinib versus zanubrutinib; neutropenia (20.4% v 34.7%) was less common with ibrutinib versus zanubrutinib (cohort 1). Zanubrutinib was associated with lower risk of AE-related treatment discontinuation. Overall, these findings confirm the long-term response quality and tolerability associated with zanubrutinib. FAU - Dimopoulos, Meletios A AU - Dimopoulos MA AUID- ORCID: 0000-0001-8990-3254 AD - National and Kapodistrian University of Athens, Athens, Greece. FAU - Opat, Stephen AU - Opat S AUID- ORCID: 0000-0002-0308-6458 AD - Monash Health & Monash University, Clayton, VIC, Australia. FAU - D'Sa, Shirley AU - D'Sa S AD - Centre for Waldenstrom's Macroglobulinemia & Associated Disorders, University College London Hospital Foundation Trust, London, United Kingdom. FAU - Jurczak, Wojciech AU - Jurczak W AD - Maria Sklodowska-Curie National Institute of Oncology, Krakow, Poland. FAU - Lee, Hui-Peng AU - Lee HP AD - Flinders Medical Centre, Adelaide, SA, Australia. FAU - Cull, Gavin AU - Cull G AD - Sir Charles Gairdner Hospital, University of Western Australia, Perth, WA, Australia. FAU - Owen, Roger G AU - Owen RG AD - St James University Hospital, Leeds, United Kingdom. FAU - Marlton, Paula AU - Marlton P AUID- ORCID: 0000-0003-2512-917X AD - Princess Alexandra Hospital and University of Queensland, Brisbane, QLD, Australia. FAU - Wahlin, Bjorn E AU - Wahlin BE AUID- ORCID: 0000-0003-3566-8847 AD - Karolinska Universitetssjukhuset & Karolinska Institutet, Stockholm, Sweden. FAU - Garcia-Sanz, Ramon AU - Garcia-Sanz R AUID- ORCID: 0000-0003-4120-2787 AD - Hospital Universitario de Salamanca, Salamanca, Spain. FAU - McCarthy, Helen AU - McCarthy H AUID- ORCID: 0009-0001-7170-0990 AD - Royal Bournemouth & Christchurch Hospital, Bournemouth, United Kingdom. FAU - Mulligan, Stephen AU - Mulligan S AUID- ORCID: 0000-0003-1928-2098 AD - Royal North Shore Hospital, Sydney, NSW, Australia. FAU - Tedeschi, Alessandra AU - Tedeschi A AD - ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Castillo, Jorge J AU - Castillo JJ AUID- ORCID: 0000-0001-9490-7532 AD - Dana-Farber Cancer Institute, Boston, MA. FAU - Czyz, Jaroslaw AU - Czyz J AUID- ORCID: 0000-0002-4178-7837 AD - Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland. FAU - Fernandez de Larrea, Carlos AU - Fernandez de Larrea C AUID- ORCID: 0000-0003-4930-9255 AD - Hospital Clinic de Barcelona, IDIBAPS, Barcelona, Spain. FAU - Belada, David AU - Belada D AD - FN Hradec Kralove, Hradec Kralove, Czechia. FAU - Libby, Edward AU - Libby E AD - Fred Hutchinson Cancer Center, Seattle, WA. FAU - Matous, Jeffrey AU - Matous J AD - Colorado Blood Cancer Institute, Denver, CO. FAU - Motta, Marina AU - Motta M AUID- ORCID: 0000-0003-3663-8092 AD - AO Spedali Civili di Brescia, Lombardia, Italy. FAU - Siddiqi, Tanya AU - Siddiqi T AUID- ORCID: 0000-0001-5292-8298 AD - City of Hope National Medical Center, Duarte, CA. FAU - Tani, Monica AU - Tani M AD - Ospedale Civile Santa Maria delle Croci, AUSL Ravenna, Ravenna, Italy. FAU - Trneny, Marek AU - Trneny M AUID- ORCID: 0000-0002-6952-6073 AD - Vseobecna fakultni nemocnice v Praze, Prague, Czechia. FAU - Minnema, Monique C AU - Minnema MC AUID- ORCID: 0000-0002-3139-8379 AD - University Medical Center Utrecht, Utrecht, the Netherlands. FAU - Buske, Christian AU - Buske C AUID- ORCID: 0000-0002-9782-9012 AD - Institute of Experimental Cancer Research -CCC Ulm-Universitatsklinikum Ulm, Ulm, Baden-Wurttemberg, Germany. FAU - Leblond, Veronique AU - Leblond V AD - Sorbonne University, Pitie Salpetriere Hospital, Paris, France. FAU - Treon, Steven P AU - Treon SP AUID- ORCID: 0000-0001-6393-6154 AD - Dana-Farber Cancer Institute, Boston, MA. FAU - Trotman, Judith AU - Trotman J AUID- ORCID: 0000-0001-8009-4593 AD - Concord Repatriation General Hospital, Sydney, NSW, Australia. FAU - Chan, Wai Y AU - Chan WY AD - BeiGene USA, Inc, San Mateo, CA. FAU - Schneider, Jingjing AU - Schneider J AD - BeiGene USA, Inc, San Mateo, CA. FAU - Allewelt, Heather AU - Allewelt H AD - BeiGene USA, Inc, San Mateo, CA. FAU - Patel, Sheel AU - Patel S AUID- ORCID: 0009-0005-7873-6653 AD - BeiGene USA, Inc, San Mateo, CA. FAU - Cohen, Aileen AU - Cohen A AD - BeiGene USA, Inc, San Mateo, CA. FAU - Tam, Constantine S AU - Tam CS AUID- ORCID: 0000-0002-9759-5017 AD - Monash Health & Monash University, Clayton, VIC, Australia. AD - The Alfred Hospital, Melbourne, VIC, Australia. LA - eng SI - ClinicalTrials.gov/NCT03053440 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial DEP - 20230721 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - AG9MHG098Z (zanubrutinib) RN - 1X70OSD4VX (ibrutinib) RN - 0 (Piperidines) RN - 0 (Pyrimidines) SB - IM MH - Humans MH - *Waldenstrom Macroglobulinemia/drug therapy/genetics MH - Piperidines/therapeutic use MH - Pyrimidines/adverse effects PMC - PMC10666987 COIS- The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Constantine S. Tam Honoraria: Janssen-Cilag, AbbVie, Novartis, BeiGene, Pharmacyclics, Roche/Genentech, Loxo/Lilly Consulting or Advisory Role: Janssen, Loxo, Roche, BeiGene, AbbVie Research Funding: Janssen-Cilag (Inst), AbbVie (Inst), BeiGene (Inst) No other potential conflicts of interest were reported. EDAT- 2023/07/21 19:10 MHDA- 2023/11/17 15:29 PMCR- 2024/11/20 CRDT- 2023/07/21 16:02 PHST- 2024/11/20 00:00 [pmc-release] PHST- 2023/11/17 15:29 [medline] PHST- 2023/07/21 19:10 [pubmed] PHST- 2023/07/21 16:02 [entrez] AID - JCO.22.02830 [pii] AID - 10.1200/JCO.22.02830 [doi] PST - ppublish SO - J Clin Oncol. 2023 Nov 20;41(33):5099-5106. doi: 10.1200/JCO.22.02830. Epub 2023 Jul 21.