Ibrutinib monotherapy outside of clinical trial setting in Waldenström macroglobulinaemia: practice patterns, toxicities and outcomes.

Adenine / analogs & derivatives Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors Aged Aged, 80 and over Antineoplastic Agents / administration & dosage Disease Progression Dose-Response Relationship, Drug Female Follow-Up Studies Hematologic Diseases / chemically induced Humans Immunoglobulin M / blood Kaplan-Meier Estimate Male Middle Aged Piperidines Practice Patterns, Physicians' / statistics & numerical data Protein Kinase Inhibitors / administration & dosage Pyrazoles / administration & dosage Pyrimidines / administration & dosage Salvage Therapy / methods Treatment Outcome Waldenstrom Macroglobulinemia / drug therapy

Bruton tyrosine kinase inhibitors IgM rebound phenomenon adverse effects lymphoplasmacytic lymphoma response

Journal

British journal of haematology

ISSN: 1365-2141

Titre abrégé: Br J Haematol

Pays: England

ID NLM: 0372544

Informations de publication

Date de publication:
02 2020

Historique:

received: 09 03 2019

accepted: 28 06 2019

pubmed: 31 8 2019

medline: 25 7 2020

entrez: 31 8 2019

Statut: ppublish

Résumé

Ibrutinib-related data in Waldenström macroglobulinaemia (WM) remain sparse, particularly outside of trials. We report on 80 patients [previously treated, n = 67 (84%), treatment-naïve, 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.

Identifiants

DOI: 10.1111/bjh.16168 PMID: 31468508

pubmed: 31468508

doi: 10.1111/bjh.16168

doi:

Substances chimiques

Antineoplastic Agents 0

Immunoglobulin M 0

Piperidines 0

Protein Kinase Inhibitors 0

Pyrazoles 0

Pyrimidines 0

ibrutinib 1X70OSD4VX

Agammaglobulinaemia Tyrosine Kinase EC 2.7.10.2

BTK protein, human EC 2.7.10.2

Adenine JAC85A2161

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

394-403

Informations de copyright

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