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 language | English (US) |
|---|---|
| Pages (from-to) | 98-105 |
| Number of pages | 8 |
| Journal | British Journal of Haematology |
| Volume | 179 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 1 2017 |
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Keywords
- IgM monoclonal gammopathy
- indolent lymphoma
- MYD88
ASJC Scopus subject areas
- Hematology
Cite this
Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia. / Paludo, Jonas; Abeykoon, Jithma P.; Kumar, Shaji K; Shreders, Amanda; Ailawadhi, Sikander; Gertz, Morie; Kourelis, Taxiarchis; King, Rebecca; Reeder, Craig B.; Leung, Nelson; Kyle, Robert A.; Buadi, Francis K.; Habermann, Thomas Matthew; Dingli, David M; Witzig, Thomas Elmer; Dispenzieri, Angela; Lacy, Martha; Go, Ronald S.; Lin, Yi; Gonsalves, Wilson; Warsame, Rahma; Lust, John A.; Rajkumar, S Vincent; Ansell, Stephen Maxted; Kapoor, Prashant.
In: British Journal of Haematology, Vol. 179, No. 1, 01.10.2017, p. 98-105.Research output: Contribution to journal › Article
}
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 -