Long-term follow-up of ibrutinib monotherapy in symptomatic, previously treated patients with Waldenström macroglobulinemia Journal Article


Authors: Treon, S. P.; Meid, K.; Gustine, J.; Yang, G.; Xu, L.; Liu, X.; Patterson, C. J.; Hunter, Z. R.; Branagan, A. R.; Laubach, J. P.; Ghobrial, I. M.; Palomba, M. L.; Advani, R.; Castillo, J. J.
Article Title: Long-term follow-up of ibrutinib monotherapy in symptomatic, previously treated patients with Waldenström macroglobulinemia
Abstract: PURPOSE We report the long-term findings and final analysis of a pivotal multicenter trial of ibrutinib monotherapy in previously treated patients with Waldenström macroglobulinemia (WM). PATIENTS AND METHODS Sixty-three symptomatic patients with median prior therapies of two (range, one to nine therapies), of whom 40% were refractory to their previous therapy, received ibrutinib at 420 mg/d. Dose reduction was permitted for toxicity. RESULTS The median follow-up was 59 months, and overall and major response rates were 90.5% and 79.4%, respectively. At best response, median serum immunoglobulin M declined from 3,520 to 821 mg/dL, bone marrow disease involvement declined from 60% to 20%, and hemoglobin rose from 10.3 to 14.2 g/dL (P, .001 for all comparisons). Responses were impacted by mutated (Mut) MYD88 and CXCR4 status. Patients with MYD88Mut, wild-type (WT) CXCR4 showed higher major (97.2% v 68.2%; P, .0001) and very good partial (47.2% v 9.1%; P, .01) response rates and a shorter time to major response (1.8 v 4.7 months; P 5 .02) versus patients with MYD88MutCXCR4Mut. Conversely, four patients who had MYD88WT disease showed no major responses. The median 5-year progression-free survival (PFS) rate for all patients was not reached, and was 70% and 38% for those with MYD88MutCXCR4WT and MYD88MutCXCR4Mut WM, respectively (P 5 .02). In patients with MYD88WT, the median PFS was 0.4 years (P, .01 for three-way comparisons). The 5-year overall survival rate for all patients was 87%. Grade $ 3 adverse events in more than one patient at least possibly related included neutropenia (15.9%), thrombocytopenia (11.1%), and pneumonia (3.2%). Eight patients (12.7%) experienced atrial arrhythmia, and seven of the eight continued therapy with medical management. CONCLUSION Ibrutinib is highly active and produces long-term disease control in previously treated patients with WM. Treatment is tolerable. Response depth, time to major response, and PFS are impacted by MYD88 and CXCR4 mutation status. © 2020 by American Society of Clinical Oncology
Journal Title: Journal of Clinical Oncology
Volume: 39
Issue: 6
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2021-02-20
Start Page: 565
End Page: 575
Language: English
DOI: 10.1200/jco.20.00555
PUBMED: 32931398
PROVIDER: scopus
PMCID: PMC8078354
DOI/URL:
Notes: Article -- Export Date: 1 April 2021 -- Source: Scopus
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  1. Maria Lia Palomba
    439 Palomba