Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia

Jonas Paludo, Jithma P. Abeykoon, Shaji K Kumar, Amanda Shreders, Sikander Ailawadhi, Morie Gertz, Taxiarchis Kourelis, Rebecca King, Craig B. Reeder, Nelson Leung, Robert A. Kyle, Francis K. Buadi, Thomas Matthew Habermann, David M Dingli, Thomas Elmer Witzig, Angela Dispenzieri, Martha Lacy, Ronald S. Go, Yi Lin, Wilson GonsalvesRahma Warsame, John A. Lust, S Vincent Rajkumar, Stephen Maxted Ansell, Prashant Kapoor

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 (95% confidence interval [CI]: 15–51) and 50 (95% CI: 35–60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23–not reached [NR]) and NR (95% CI: 37–NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88L265P. The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients’ MYD88 status.

Original languageEnglish (US)
Pages (from-to)98-105
Number of pages8
JournalBritish Journal of Haematology
Volume179
Issue number1
DOIs
StatePublished - Oct 1 2017

Fingerprint

Waldenstrom Macroglobulinemia
Cyclophosphamide
Dexamethasone
Confidence Intervals
Disease-Free Survival
Therapeutics
Mutation
Neutropenia
Thrombocytopenia
Rituximab
Genotype
Infection

Keywords

  • IgM monoclonal gammopathy
  • indolent lymphoma
  • MYD88

ASJC Scopus subject areas

  • Hematology

Cite this

@article{4e9f77a253e646769e93d91f08deb62a,
title = "Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-na{\"i}ve patients with Waldenstrom macroglobulinemia",
abstract = "The management of Waldenstr{\"o}m macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87{\%}. The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 (95{\%} confidence interval [CI]: 15–51) and 50 (95{\%} CI: 35–60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96{\%}, and the median PFS and TTNT were 34 months (95{\%} CI: 23–not reached [NR]) and NR (95{\%} CI: 37–NR), respectively. Twenty-five (86{\%}) of 29 genotyped patients harbored MYD88L265P. The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20{\%}), thrombocytopenia (7{\%}) and infections (3{\%}). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients’ MYD88 status.",
keywords = "IgM monoclonal gammopathy, indolent lymphoma, MYD88",
author = "Jonas Paludo and Abeykoon, {Jithma P.} and Kumar, {Shaji K} and Amanda Shreders and Sikander Ailawadhi and Morie Gertz and Taxiarchis Kourelis and Rebecca King and Reeder, {Craig B.} and Nelson Leung and Kyle, {Robert A.} and Buadi, {Francis K.} and Habermann, {Thomas Matthew} and Dingli, {David M} and Witzig, {Thomas Elmer} and Angela Dispenzieri and Martha Lacy and Go, {Ronald S.} and Yi Lin and Wilson Gonsalves and Rahma Warsame and Lust, {John A.} and Rajkumar, {S Vincent} and Ansell, {Stephen Maxted} and Prashant Kapoor",
year = "2017",
month = "10",
day = "1",
doi = "10.1111/bjh.14826",
language = "English (US)",
volume = "179",
pages = "98--105",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia

AU - Paludo, Jonas

AU - Abeykoon, Jithma P.

AU - Kumar, Shaji K

AU - Shreders, Amanda

AU - Ailawadhi, Sikander

AU - Gertz, Morie

AU - Kourelis, Taxiarchis

AU - King, Rebecca

AU - Reeder, Craig B.

AU - Leung, Nelson

AU - Kyle, Robert A.

AU - Buadi, Francis K.

AU - Habermann, Thomas Matthew

AU - Dingli, David M

AU - Witzig, Thomas Elmer

AU - Dispenzieri, Angela

AU - Lacy, Martha

AU - Go, Ronald S.

AU - Lin, Yi

AU - Gonsalves, Wilson

AU - Warsame, Rahma

AU - Lust, John A.

AU - Rajkumar, S Vincent

AU - Ansell, Stephen Maxted

AU - Kapoor, Prashant

PY - 2017/10/1

Y1 - 2017/10/1

N2 - The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 (95% confidence interval [CI]: 15–51) and 50 (95% CI: 35–60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23–not reached [NR]) and NR (95% CI: 37–NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88L265P. The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients’ MYD88 status.

AB - The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 (95% confidence interval [CI]: 15–51) and 50 (95% CI: 35–60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23–not reached [NR]) and NR (95% CI: 37–NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88L265P. The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients’ MYD88 status.

KW - IgM monoclonal gammopathy

KW - indolent lymphoma

KW - MYD88

UR - http://www.scopus.com/inward/record.url?scp=85029798884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029798884&partnerID=8YFLogxK

U2 - 10.1111/bjh.14826

DO - 10.1111/bjh.14826

M3 - Article

C2 - 28786474

AN - SCOPUS:85029798884

VL - 179

SP - 98

EP - 105

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 1

ER -