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

Jithma P. Abeykoon, Saurabh Zanwar, Stephen Maxted Ansell, Morie Gertz, Shaji K Kumar, Michelle Manske, Anne J Novak, Rebecca King, Patricia T Greipp, Ronald Go, David Inwards, Eli Muchtar, Thomas Matthew Habermann, Thomas Elmer Witzig, Carrie A Thompson, David M Dingli, Martha Lacy, Nelson Leung, Angela Dispenzieri, Wilson GonsalvesRahma Warsame, Robert A. Kyle, S Vincent Rajkumar, Sameer A Parikh, Prashant Kapoor

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalBritish journal of haematology
DOIs
StateAccepted/In press - Jan 1 2019

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Waldenstrom Macroglobulinemia
Clinical Trials
Confidence Intervals
Disease-Free Survival
Immunoglobulin M
Therapeutics
Salvage Therapy
Atrial Fibrillation
Fatigue
Disease Progression
PCI 32765
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

@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 = "adverse effects, Bruton tyrosine kinase inhibitors, IgM rebound phenomenon, lymphoplasmacytic lymphoma, response",
author = "Abeykoon, {Jithma P.} and Saurabh Zanwar and Ansell, {Stephen Maxted} and Morie Gertz and Kumar, {Shaji K} and Michelle Manske and Novak, {Anne J} and Rebecca King and Greipp, {Patricia T} and Ronald Go and David Inwards and Eli Muchtar and Habermann, {Thomas Matthew} and Witzig, {Thomas Elmer} and Thompson, {Carrie A} and Dingli, {David M} and Martha Lacy and Nelson Leung and Angela Dispenzieri and Wilson Gonsalves and Rahma Warsame and Kyle, {Robert A.} and Rajkumar, {S Vincent} and Parikh, {Sameer A} and Prashant Kapoor",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/bjh.16168",
language = "English (US)",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",

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TY - JOUR

T1 - Ibrutinib monotherapy outside of clinical trial setting in Waldenström macroglobulinaemia

T2 - practice patterns, toxicities and outcomes

AU - Abeykoon, Jithma P.

AU - Zanwar, Saurabh

AU - Ansell, Stephen Maxted

AU - Gertz, Morie

AU - Kumar, Shaji K

AU - Manske, Michelle

AU - Novak, Anne J

AU - King, Rebecca

AU - Greipp, Patricia T

AU - Go, Ronald

AU - Inwards, David

AU - Muchtar, Eli

AU - Habermann, Thomas Matthew

AU - Witzig, Thomas Elmer

AU - Thompson, Carrie A

AU - Dingli, David M

AU - Lacy, Martha

AU - Leung, Nelson

AU - Dispenzieri, Angela

AU - Gonsalves, Wilson

AU - Warsame, Rahma

AU - Kyle, Robert A.

AU - Rajkumar, S Vincent

AU - Parikh, Sameer A

AU - Kapoor, Prashant

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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KW - Bruton tyrosine kinase inhibitors

KW - IgM rebound phenomenon

KW - lymphoplasmacytic lymphoma

KW - response

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