@article{685eb87bc7c44acfaa62b69d328e717a,
title = "Ibrutinib monotherapy outside of clinical trial setting in Waldenstr{\"o}m macroglobulinaemia: practice patterns, toxicities and outcomes",
abstract = "Ibrutinib-related data in Waldenstr{\"o}m macroglobulinaemia (WM) remain sparse, particularly outside of trials. We report on 80 patients [previously treated, n = 67 (84%), treatment-na{\"i}ve, n = 13 (16%)] with WM, evaluated consecutively at Mayo Clinic, who received ibrutinib off-study after its approval in 2015 for WM. Overall response rate (ORR) was 91%; major-response rate (MRR) was 78%. The median time to first response and best response was 2·9 [95% confidence interval (CI): 2–4] and 5·7 (95% CI: 4–12) months, respectively. The median follow-up was 19 (95% CI: 14–21) months; 18-month progression-free survival (PFS) was 82%. The median time on therapy was 12·5 (95% CI: 9·3–16·7) months, and the median duration-of-response was 32 (range: 23–32) months. Twenty-five patients (31%) had discontinued therapy at last follow-up (68% due to treatment-related toxicities) and 18% of patients required dose reduction. Fatigue (12%) and atrial-fibrillation (11%) were common non-haematological toxicities. IgM rebound occurred in 36% of patients who abruptly discontinued ibrutinib. Following ibrutinib discontinuation, 84% of patients received subsequent treatment, achieving an ORR of 57% and MRR of 50%. The median PFS from commencement of subsequent salvage therapy was 18 months. Ibrutinib therapy, outside of clinical trials, is effective in WM, but is associated with toxicities and challenges, including IgM rebound and a high drug discontinuation rate for reasons other than disease progression.",
keywords = "Bruton tyrosine kinase inhibitors, IgM rebound phenomenon, adverse effects, lymphoplasmacytic lymphoma, response",
author = "Abeykoon, {Jithma P.} and Saurabh Zanwar and Ansell, {Stephen M.} and Gertz, {Morie A.} and Shaji Kumar and Michelle Manske and Novak, {Anne J.} and Rebecca King and Patricia Greipp and Ronald Go and David Inwards and Eli Muchtar and Thomas Habermann and Witzig, {Thomas E.} and Thompson, {Carrie A.} and David Dingli and Lacy, {Martha Q.} and Nelson Leung and Angela Dispenzieri and Wilson Gonsalves and Rahma Warsame and Kyle, {Robert A.} and Vincent Rajkumar and Parikh, {Sameer A.} and Prashant Kapoor",
note = "Funding Information: Dr. Gertz: personal fees from Ionis/Akcea, Alnylam, Prothena, Celgene, Janssen, Annexon, Appellis, Amgen, Medscape, Physicians Education Resource, Abbvie (for Data Safety Monitoring Board), Research to Practice, grants and personal fees from Spectrum, speaker fees from Teva, Johnson and Johnson; Medscape, DAVA oncology; Advisory Board for Pharmacyclics, Advisory Board for Proclara outside the submitted work; Royalties from Springer Publishing Grant Funding Amyloidosis Foundation; International Waldenstrom Foundation, NCI SPORE MM SPORE 5P50 CA186781‐04. Dr. Dispenzieri: research funding from Jannsen, Takeda, Celgene, Pfizer, Alnylam and GSK, and serves on the advisory board for Takeda and Intellia. Dr. Kumar: research funding for clinical trials to the institution from Celgene, Takeda, Janssen, BMS, Sanofi, KITE, Merck, Abbvie, Medimmune, Novartis, Roche‐Genentech, Amgen Consulting/Advisory Board participation (with no personal payments); Celgene, Takeda, Janssen, KITE, Merck, Abbvie, Medimmune,Genentech, Amgen (with personal payment) Oncopeptides, Adaptive. Dr. Dingli: serves as a consultant for Alexion, Takeda, Jansen and Rigel. Dr. Witzig: research funding to conduct clinical trials from Celgene, Spectrum and Acerta and has served on the Advisory Board (personally uncompensated) for Incyte, Seattle Genetics, Abbvie, Morphosys, Spectrum and Immune Design, for which Dr. Witzig was personally compensated. Dr. Parikh: research funding from Pharmacyclics, MorphoSys, Janssen, AstraZeneca and Ascentage Pharma for clinical studies in which he is a principal investigator. Dr. Parikh has also participated in Advisory Board meetings of Pharmacyclics, AstraZeneca, Genentech, Gilead and AbbVie (was not personally compensated for his participation). Dr. Kapoor is principal investigator of trials for which Mayo Clinic receives funding from GSK, Janssen, Sanofi, Amgen and Takeda. The remaining authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2019 British Society for Haematology and John Wiley & Sons Ltd",
year = "2020",
month = feb,
day = "1",
doi = "10.1111/bjh.16168",
language = "English (US)",
volume = "188",
pages = "394--403",
journal = "British journal of haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "3",
}