Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Feb 25;9(4):722-728.
doi: 10.1182/bloodadvances.2024014115.

Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia

Benjamin M Heyman  1 , Stephen S Opat  2 , Björn E Wahlin  3 , Meletios-Athanasios C Dimopoulos  4 , Jorge J Castillo  5 , Alessandra Tedeschi  6 , Constantine S Tam  7   8 , Christian Buske  9 , Roger G Owen  10 , Véronique Leblond  11 , Judith Trotman  12 , Gisoo Barnes  13 , Wai Y Chan  13 , Jingjing Schneider  13 , Heather Allewelt  13 , Aileen Cohen  13 , Jeffrey V Matous  14
Affiliations
Clinical Trial

Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia

Benjamin M Heyman et al. Blood Adv. .

Abstract

Peripheral neuropathy (PN) is a significant cause of morbidity associated with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of zanubrutinib with ibrutinib in patients with WM. This ad hoc analysis examined treatment outcomes with zanubrutinib or ibrutinib on PN symptoms associated with WM in patients enrolled in ASPEN. Logistic regression was performed between PN symptom resolution and several predictors. Health-related quality of life (HRQOL) was assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Forty-nine patients with PN symptoms were included (zanubrutinib treated, n = 27; ibrutinib treated, n = 22). Overall, 35 patients (71.4%) experienced resolution of PN symptoms, with a median time to resolution of 10.1 months (range, 1-46.8). In cohort 1 (MYD88 mutation), the median time to PN symptom resolution was 4.6 months (range, 1.1-46.8) with zanubrutinib and 14.1 months (range, 1-44) with ibrutinib. Logistic regression demonstrated a significant relationship between PN symptom resolution and both major response and lower baseline anti-myelin-associated glycoprotein antibody levels. Patients with PN symptom resolution had greater improvement in HRQOL. Physical functioning improved in patients with PN symptom resolution and was unchanged in patients without resolution. Improvements observed in PN symptoms may be in response to a reduction in immunoglobulin M. Although further investigation is required, this analysis supports the potential use and further exploration of Bruton tyrosine kinase inhibitors to treat PN symptoms in patients with WM. This trial was registered at www.clinicaltrials.gov as #NCT03053440.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: B.M.H. reports research funding from AbbVie, Century Therapeutics, Oncternal Therapeutics, and Roche; and advisory board fees from AstraZeneca, BeiGene, and Epizyme, Inc. S.S.O. reports consulting fees from AbbVie, Antengene, AstraZeneca, BeiGene, Bristol Myers Squibb (BMS), CSL Behring, Gilead, Merck, Novartis, Janssen, Roche, and Takeda; research funding from AbbVie, AstraZeneca, BeiGene, BMS, Gilead, Janssen, Merck, Novartis, Pharmacyclics, Roche, and Takeda; honoraria from AbbVie, AstraZeneca, BeiGene, BMS, Gilead, Janssen, Merck, Novartis, Roche, and Takeda; and membership on an entity’s board of directors or advisory committees in AbbVie, AstraZeneca, BeiGene, BMS, Gilead, Janssen, Merck, Novartis, Roche, and Takeda outside the submitted work. B.E.W. reports stocks in Genmab. M.-A.A.D. reports advisory board fees and honoraria from Amgen, AbbVie, BMS, BeiGene, Janssen, GSK, Menarini, Takeda, Regeneron, and Sanofi. J.J.C. reports research funding from AbbVie, AstraZeneca, BeiGene, Cellectar, Loxo, and Pharmacyclics; and consultancy fees from AbbVie, AstraZeneca, Avilar, BeiGene, Cellectar, Janssen, Kite, Loxo, Mustang Bio, and Pharmacyclics. A.T. reports consultancy fees from BeiGene, AstraZeneca, AbbVie, and Janssen; honoraria from BeiGene, AstraZeneca, AbbVie, and Janssen; speakers bureau fees from BeiGene, AstraZeneca, AbbVie, and Janssen; and travel, accommodations, and expenses from BeiGene, AstraZeneca, AbbVie, and Janssen. C.S.T. reports research funding from Janssen, AbbVie, and BeiGene; and honoraria from Janssen, AbbVie, BeiGene, Loxo, and AstraZeneca. C.B. reports consultancy, honoraria, advisory board, and travel expenses from Roche/Genentech, Janssen, BeiGene, Novartis, Pfizer, Incyte, AbbVie, Gilead, Celltrion, MorphoSys, Regeneron, Sobi, and Lilly. R.G.O. reports consultancy fees from BeiGene and Janssen; honoraria from BeiGene, Janssen, and AstraZeneca; and meetings/travel expenses from BeiGene. V.L. reports consultancy fees from BeiGene, AbbVie, Janssen, and Merck Sharp & Dohme; and honoraria from Pfizer, BeiGene, AstraZeneca, and Amgen. J.T. reports research funding from BeiGene, Janssen, Pharmacyclics, Roche, Celgene/BMS, and Cellectar; and advisory board fees from BeiGene. G.B. and J.S. report employment with BeiGene. W.Y.C. reports employment with BeiGene; and equity in BeiGene and BMS. H.A. reports employment and is an equity holder in a publicly traded company with BeiGene and Nkarta Therapeutics; and patents and royalties with St Jude Children’s Research Hospital. A.C. reports consultancy and is an equity holder in BeiGene. J.V.M. reports consultancy fees from Waldenström macroglobulinemia advisory committee of BeiGene.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Disposition of patients with PN symptoms in ASPEN.aAn additional patient with R/R disease in each cohort 1 group was randomized but did not receive treatment due to acute kidney injury and central nervous system lymphoma. BID, twice daily; QD, once daily; R, randomized; R/R, relapsed/refractory; TN, treatment naive.
See this image and copyright information in PMC

References

    1. Castillo JJ, Treon SP. What is new in the treatment of Waldenstrom macroglobulinemia? Leukemia. 2019;33(11):2555–2562. - PubMed
    1. Treon SP, Xu L, Guerrera ML, et al. Genomic landscape of Waldenström macroglobulinemia and its impact on treatment strategies. J Clin Oncol. 2020;38(11):1198–1208. - PMC - PubMed
    1. Paba-Prada CE, Banwait R, Treon S, Ghobrial IM. Incidence of peripheral neuropathy in Waldenström macroglobulinemia patients at diagnosis. Blood. 2011;118(21):3692.
    1. Klein CJ, Moon JS, Mauermann ML, et al. The neuropathies of Waldenstrom's macroglobulinemia (WM) and IgM-MGUS. Can J Neurol Sci. 2011;38(2):289–295. - PMC - PubMed
    1. Levine T, Pestronk A, Florence J, et al. Peripheral neuropathies in Waldenstrom's macroglobulinaemia. J Neurol Neurosurg Psychiatry. 2006;77(2):224–228. - PMC - PubMed

MeSH terms

Associated data