Bortezomib‐based therapy is effective and well tolerated in frontline and multiply pre‐treated Waldenström macroglobulinaemia including BTKi failures: A real‐world analysis

Abstract

Waldenström macroglobulinemia (WM) is a rare, incurable low grade lymphoma following a relapsing trajectory. Management strategies have evolved with the introduction of targeted therapy including new classes of Bruton tyrosine kinase inhibitor (BTKi). Treatment may however be limited particularly at relapse by a lack of drug availability and tolerability. We assessed the real-world efficacy and tolerability of bortezomib-containing regimens in patients with WM at frontline and relapse including those with prior BTKi resistance. Forty-one patients were identified with 44 bortezomib-containing regimens administered (n = 12 frontline, n = 32 relapse). Of patients treated at relapse, the median prior lines of therapy was 3 (range 1-7). 24% (10/41) of the cohort were refractory or intolerant to BTKi prior to bortezomib delivery. The median follow-up after bortezomib administration was 34 months (range 0-131). Overall response rate was 88%; 2-year overall survival and progression-free survival were 90% (95% confidence interval [CI] 73-96) and 76% (95% CI 55-87), respectively. Median time-to-next-treatment was 66 months. Neuropathy (grade 1-2) occurred in 24% (8/34) and did not result in treatment cessation in any case. Gastrointestinal disturbance occurred in 7% (3/41). Treatment discontinuations were rare (1/44; 2%), suggesting a manageable safety profile. Major response rate was comparable in those with prior BTKi compared with those without (75% [6/8] vs 84% [27/32], p = 0.61). Bortezomib should be considered as a treatment modality particularly in those who are refractory to BTKi.

IgM-Associated Cryoglobulinaemia

“…Historically, there has been concern to treat emergent neurotoxicity with the use of bortezomib, which may be a particular concern in those with cryoglobulinaemic peripheral neuropathy. However weakly, subcutaneous administration and close monitoring may ameliorate the risk and have been shown to be efficacious in WM [32]. Effective depletion of clonal disease by bortezomib is likely to supersede its potential neurotoxicty.…”

The Rory Morrison WMUK Registry for Waldenström macroglobulinaemia: The growth of a national registry for a rare disorder

“…Treatment options include combination chemoimmunotherapy and an increasing range of targeted therapies. 8,9 In the UK, the use of the covalent Bruton's tyrosine kinase inhibitors (BTKi) ibrutinib, acalabrutinib and zanubrutinib has grown via national funding mechanisms and clinical trials. British Society of Haematology guidelines recommend the use of rituximabcontaining combinations as part of front-line therapy and chemoimmunotherapy or targeted therapies in the relapsed setting.…”

“…It may be associated with several important clinical disorders, collectively termed ‘IgM monoclonal gammopathies of clinical significance’ 7 ; their exact prevalence is not established and remains an unmet clinical need. Treatment options include combination chemoimmunotherapy and an increasing range of targeted therapies 8,9 . In the UK, the use of the covalent Bruton's tyrosine kinase inhibitors (BTKi) ibrutinib, acalabrutinib and zanubrutinib has grown via national funding mechanisms and clinical trials.…”

Born in the UK: A registry to improve and broadcast knowledge on Waldenström macroglobulinaemia

“…Since November 2017, the RMR has grown significantly, has successfully passed into adulthood and has already given birth to numerous analyses presented at international haematology congresses and/or recently published. 5,10 With such a broadcast, we have not finished hearing about it! ORC I D Eric Durot https://orcid.org/0000-0003-3463-0089 Alain Delmer https://orcid.org/0000-0002-1430-2574…”

“…With >1300 patients registered from 22 centres; he would be impressed with how far the registry has come. Since November 2017, the RMR has grown significantly, has successfully passed into adulthood and has already given birth to numerous analyses presented at international haematology congresses and/or recently published 5,10 . With such a broadcast, we have not finished hearing about it!…”