Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia
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...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952924006931 |
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| author | Benjamin M. Heyman Stephen S. Opat Björn E. Wahlin Meletios-Athanasios C. Dimopoulos Jorge J. Castillo Alessandra Tedeschi Constantine S. Tam Christian Buske Roger G. Owen Véronique Leblond Judith Trotman Gisoo Barnes Wai Y. Chan Jingjing Schneider Heather Allewelt Aileen Cohen Jeffrey V. Matous |
| author_facet | Benjamin M. Heyman Stephen S. Opat Björn E. Wahlin Meletios-Athanasios C. Dimopoulos Jorge J. Castillo Alessandra Tedeschi Constantine S. Tam Christian Buske Roger G. Owen Véronique Leblond Judith Trotman Gisoo Barnes Wai Y. Chan Jingjing Schneider Heather Allewelt Aileen Cohen Jeffrey V. Matous |
| author_sort | Benjamin M. Heyman |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e9c661101a694756adef259216c5eca1 |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-e9c661101a694756adef259216c5eca12025-02-12T05:31:37ZengElsevierBlood Advances2473-95292025-02-0194722728Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemiaBenjamin M. Heyman0Stephen S. Opat1Björn E. Wahlin2Meletios-Athanasios C. Dimopoulos3Jorge J. Castillo4Alessandra Tedeschi5Constantine S. Tam6Christian Buske7Roger G. Owen8Véronique Leblond9Judith Trotman10Gisoo Barnes11Wai Y. Chan12Jingjing Schneider13Heather Allewelt14Aileen Cohen15Jeffrey V. Matous16Hematology, University of California San Diego, San Diego, CA; Correspondence: Benjamin M. Heyman, Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093;Department of Haematology, Lymphoma Research Group, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, AustraliaDepartment of Medicine, Karolinska Universitetssjukhuset Solna, Solna, SwedenDepartment of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra Hospital, Athens, GreeceBing Center for Waldenström’s Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MAASST Grande Ospedale Metropolitano Niguarda, Milan, ItalyAlfred Hospital, Melbourne, VIC, Australia; Central Clinical School, Monash University, Melbourne, VIC, AustraliaInstitute of Experimental Cancer Research, Comprehensive Cancer Center Ulm, University Hospital Ulm, Ulm, GermanySt James’s University Hospital, Leeds, United KingdomSorbonne University, Pitié Salpêtrière Hospital, Paris, FranceConcord Repatriation General Hospital, University of Sydney, Concord, NSW, AustraliaBeiGene USA, Inc, San Mateo, CABeiGene USA, Inc, San Mateo, CABeiGene USA, Inc, San Mateo, CABeiGene USA, Inc, San Mateo, CABeiGene USA, Inc, San Mateo, CAColorado Blood Cancer Institute, Sarah Cannon Research Institute, Denver, COAbstract: 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.http://www.sciencedirect.com/science/article/pii/S2473952924006931 |
| spellingShingle | Benjamin M. Heyman Stephen S. Opat Björn E. Wahlin Meletios-Athanasios C. Dimopoulos Jorge J. Castillo Alessandra Tedeschi Constantine S. Tam Christian Buske Roger G. Owen Véronique Leblond Judith Trotman Gisoo Barnes Wai Y. Chan Jingjing Schneider Heather Allewelt Aileen Cohen Jeffrey V. Matous Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia Blood Advances |
| title | Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia |
| title_full | Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia |
| title_fullStr | Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia |
| title_full_unstemmed | Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia |
| title_short | Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia |
| title_sort | peripheral neuropathy in the phase 3 aspen study of bruton tyrosine kinase inhibitors for waldenstrom macroglobulinemia |
| url | http://www.sciencedirect.com/science/article/pii/S2473952924006931 |
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