PMID- 32822482
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20220531
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 4
IP  - 16
DP  - 2020 Aug 25
TI  - Ixazomib, dexamethasone, and rituximab in treatment-naive patients with 
      Waldenstrom macroglobulinemia: long-term follow-up.
PG  - 3952-3959
LID - 10.1182/bloodadvances.2020001963 [doi]
AB  - Proteasome inhibition is a standard of care for the primary treatment of patients 
      with Waldenstrom macroglobulinemia (WM). We present the long-term follow-up of a 
      prospective, phase II clinical trial that evaluated the combination of ixazomib, 
      dexamethasone, and rituximab (IDR) in 26 treatment-naive patients with WM. IDR 
      was administered as 6 monthly induction cycles followed by 6 every-2-month 
      maintenance cycles. The MYD88 L265P mutation was detected in all patients, and 
      CXCR4 mutations were detected in 15 patients (58%). The median time to response 
      (TTR) and time to major response (TTMR) were 2 and 6 months, respectively. 
      Patients with and without CXCR4 mutations had median TTR of 3 months and 1 month, 
      respectively (P = .003), and median TTMR of 10 months and 3 months, respectively 
      (P = .31). The overall, major, and very good partial response (VGPR) rates were 
      96%, 77%, and 19%, respectively. The rate of VGPR in patients with and without 
      CXCR4 mutations were 7% and 36%, respectively (P = .06). The median 
      progression-free survival (PFS) was 40 months, the median duration of response 
      (DOR) was 38 months, and the median time to next treatment (TTNT) was 40 months. 
      PFS, DOR, and TTNT were not affected by CXCR4 mutational status. The safety 
      profile was excellent with no grade 4 adverse events or deaths to date. IDR 
      provides a safe and effective frontline treatment option for symptomatic patients 
      with WM. This study was registered at www.clinicaltrials.gov as #NCT02400437.
CI  - (c) 2020 by The American Society of Hematology.
FAU - Castillo, Jorge J
AU  - Castillo JJ
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
AD  - Department of Medicine, Harvard Medical School, Boston, MA.
FAU - Meid, Kirsten
AU  - Meid K
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
FAU - Flynn, Catherine A
AU  - Flynn CA
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
FAU - Chen, Jiaji
AU  - Chen J
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
FAU - Demos, Maria G
AU  - Demos MG
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
FAU - Guerrera, Maria L
AU  - Guerrera ML
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
FAU - Kofides, Amanda
AU  - Kofides A
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
FAU - Liu, Xia
AU  - Liu X
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
FAU - Munshi, Manit
AU  - Munshi M
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
FAU - Tsakmaklis, Nicholas
AU  - Tsakmaklis N
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
FAU - Patterson, Christopher J
AU  - Patterson CJ
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
FAU - Yang, Guang
AU  - Yang G
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
AD  - Department of Medicine, Harvard Medical School, Boston, MA.
FAU - Hunter, Zachary
AU  - Hunter Z
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
AD  - Department of Medicine, Harvard Medical School, Boston, MA.
FAU - Treon, Steven P
AU  - Treon SP
AD  - Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, 
      Boston, MA; and.
AD  - Department of Medicine, Harvard Medical School, Boston, MA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02400437
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Boron Compounds)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 71050168A2 (ixazomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Boron Compounds
MH  - Dexamethasone
MH  - Follow-Up Studies
MH  - Glycine/analogs & derivatives
MH  - Humans
MH  - Myeloid Differentiation Factor 88
MH  - Prospective Studies
MH  - Rituximab
MH  - *Waldenstrom Macroglobulinemia/drug therapy/genetics
PMC - PMC7448596
COIS- Conflict-of-interest disclosure: J.J.C. has received honoraria and/or research 
      funds from AbbVie, Beigene, Janssen, Kymera, Millennium, Pharmacyclics, and TG 
      Therapeutics. S.P.T. has received research funding and/or consulting fees from 
      BMS, Pharmacyclics, and Janssen. The remaining authors declare no competing 
      financial interests.
EDAT- 2020/08/22 06:00
MHDA- 2021/05/15 06:00
PMCR- 2020/08/21
CRDT- 2020/08/22 06:00
PHST- 2020/03/30 00:00 [received]
PHST- 2020/07/20 00:00 [accepted]
PHST- 2020/08/22 06:00 [entrez]
PHST- 2020/08/22 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/08/21 00:00 [pmc-release]
AID - S2473-9529(20)31155-1 [pii]
AID - 2020/ADV2020001963 [pii]
AID - 10.1182/bloodadvances.2020001963 [doi]
PST - ppublish
SO  - Blood Adv. 2020 Aug 25;4(16):3952-3959. doi: 10.1182/bloodadvances.2020001963.