PMID- 33970288
OWN - NLM
STAT- MEDLINE
DCOM- 20210820
LR  - 20210930
IS  - 1432-0584 (Electronic)
IS  - 0939-5555 (Print)
IS  - 0939-5555 (Linking)
VI  - 100
IP  - 9
DP  - 2021 Sep
TI  - Real-world comparative effectiveness of triplets containing bortezomib (B), 
      carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple 
      myeloma (RRMM) in the US.
PG  - 2325-2337
LID - 10.1007/s00277-021-04534-8 [doi]
AB  - Multiple available combinations of proteasome inhibitors, immunomodulators 
      (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple 
      myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet 
      regimens highlights the need for real-world (RW) evidence. We conducted an RW 
      comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib 
      (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus 
      dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating 
      triplet regimens in line of therapy (LOT) >/= 2 on/after 1/1/2014 was followed 
      between 1/2007 and 3/2018 in Optum's deidentified US electronic health records 
      database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; 
      regimens were compared using covariate-adjusted Cox proportional hazard models. 
      Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 
      349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) 
      with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs 
      >/=2 were identified. More patients >/=75 years received IRd (39.6%), IPd (37.8%), 
      and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 
      vs other triplets. Unadjusted median TTNT in LOT >/= 2: VRd, 13.9; KRd, 8.7; IRd, 
      11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. 
      In covariate-adjusted analysis, only KRd vs DRd was associated with a 
      significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no 
      Pd triplet was significantly different vs DPd in LOT >/= 2. Our data highlight 
      important efficacy/effectiveness gaps between results observed in phase 3 
      clinical trials and those realized in the RW.
CI  - (c) 2021. The Author(s).
FAU - Davies, Faith
AU  - Davies F
AD  - NYU Langone Health, New York, NY, USA. faith.davies@nyulangone.org.
FAU - Rifkin, Robert
AU  - Rifkin R
AD  - Rocky Mountain Cancer Centers, Denver, CO, USA.
FAU - Costello, Caitlin
AU  - Costello C
AD  - Moores Cancer Center, University of California, San Diego, CA, USA.
FAU - Morgan, Gareth
AU  - Morgan G
AD  - NYU Langone Health, New York, NY, USA.
FAU - Usmani, Saad
AU  - Usmani S
AD  - Carolinas Healthcare System, Charlotte, NC, USA.
FAU - Abonour, Rafat
AU  - Abonour R
AD  - Indiana University, Indianapolis, IN, USA.
FAU - Palumbo, Antonio
AU  - Palumbo A
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Romanus, Dorothy
AU  - Romanus D
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Hajek, Roman
AU  - Hajek R
AD  - University Hospital Ostrava and Faculty of Medicine, University of Ostrava, 
      Ostrava, Czech Republic.
FAU - Terpos, Evangelos
AU  - Terpos E
AD  - University of Athens School of Medicine, Athens, Greece.
FAU - Cherepanov, Dasha
AU  - Cherepanov D
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Stull, Dawn Marie
AU  - Stull DM
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Huang, Hui
AU  - Huang H
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Leleu, Xavier
AU  - Leleu X
AD  - CHU la Miletrie, Poiters, France.
FAU - Berdeja, Jesus
AU  - Berdeja J
AD  - Tennessee Oncology, Sarah Cannon Research Institute, Nashville, TN, USA.
FAU - Lee, Hans C
AU  - Lee HC
AD  - University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
FAU - Weisel, Katja
AU  - Weisel K
AD  - Department of Oncology, Hematology and Bone Marrow Transplantation with Section 
      of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - Thompson, Michael
AU  - Thompson M
AD  - Aurora Cancer Center, Advocate Aurora Health, Milwaukee, WI, USA.
FAU - Boccadoro, Mario
AU  - Boccadoro M
AD  - Azienda Ospedaliera Citta della Salute e della Scienza, Torino, Italy.
FAU - Zonder, Jeffrey
AU  - Zonder J
AD  - Karmanos Cancer Institute, Detroit, MI, USA.
FAU - Cook, Gordon
AU  - Cook G
AD  - Leeds Teaching Hospitals NHS Trust, Leeds, UK.
FAU - Puig, Noemi
AU  - Puig N
AD  - Salamanca University Hospital, Salamanca, Spain.
FAU - Vela-Ojeda, Jorge
AU  - Vela-Ojeda J
AD  - Hospital de Especialidades Centro Medico Nacional la Raza, Mexico City, Mexico.
FAU - Farrelly, Eileen
AU  - Farrelly E
AD  - Xcenda, Palm Harbor, FL, USA.
FAU - Raju, Aditya
AU  - Raju A
AD  - Xcenda, Palm Harbor, FL, USA.
FAU - Blazer, Marlo
AU  - Blazer M
AD  - Xcenda, Palm Harbor, FL, USA.
FAU - Chari, Ajai
AU  - Chari A
AD  - Icahn School of Medicine at Mount Sinai, New York, NY, USA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20210510
PL  - Germany
TA  - Ann Hematol
JT  - Annals of hematology
JID - 9107334
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Boron Compounds)
RN  - 0 (Oligopeptides)
RN  - 4Z63YK6E0E (daratumumab)
RN  - 69G8BD63PP (Bortezomib)
RN  - 71050168A2 (ixazomib)
RN  - 72X6E3J5AR (carfilzomib)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Boron Compounds/*therapeutic use
MH  - Bortezomib/*therapeutic use
MH  - Female
MH  - Glycine/*analogs & derivatives/therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Oligopeptides/*therapeutic use
MH  - Retrospective Studies
MH  - Treatment Outcome
PMC - PMC8357697
OTO - NOTNLM
OT  - Bortezomib
OT  - Carfilzomib
OT  - Daratumumab
OT  - Ixazomib
OT  - Lenalidomide
OT  - Pomalidomide
OT  - Proteasome inhibitor triplet therapy
OT  - Real-world
OT  - Relapsed refractory multiple myeloma
COIS- FD reports honoraria from Adaptive, Celgene Corporation, Janssen, Oncopeptide, 
      Roche, Sanofi, and Takeda; consultancy or research funding from Celgene 
      Corporation, Janssen, Oncopeptide, Roche, Sanofi, and Takeda. RR is a current 
      equity holder in McKesson; advisory board member for Takeda, Amgen, and BMS 
      (Celgene); investigator for AbbVie; and consultancy for Takeda, Amgen, Celgene, 
      BMS, Mylan, Coherus, BioSciences, and Fresenius. CC receives grants and 
      honorarium from Takeda and BMS and honorarium from Karyopharm and Oncopeptides. 
      GM has received funding from Celgene, BMS, Sanofi, Karyopharm, Janssen, Roche, 
      and Genentech. SU receives research funding from Amgen, Array Biopharma, BMS, 
      Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, 
      and Takeda; SU receives consulting fees from Abbvie, Amgen, BMS, Celgene, GSK, 
      Genentech/Roche, Janssen, Karyopharm, Merck, Oncopeptides, Sanofi, Seattle 
      Genetics, SkylineDx, and Takeda; SU receives speaking fees from Celgene, Janssen, 
      Sanofi, and Takeda. RA reports grants from Takeda. AP is an employee of GSK. DC, 
      DMS, HH, and DR are or were all employees of Millennium Pharmaceuticals, Inc., a 
      wholly own subsidiary of Takeda Pharmaceutical Company Limited, at the time this 
      research was conducted. RH receives consulting honoraria and/or research support 
      received from Takeda, Novartis, Celgene, PharmaMar, Oncopeptides, Janssen, Amgen, 
      AbbVie, and Bristol-Myers Squibb. ET declares honoraria from Amgen, BMS, Janssen, 
      Celgene, Takeda, Genesis Pharma, and Sanofi and research funding from Janssen, 
      Amgen, Sanofi, Takeda, and Genesis Pharma. XL receives honoraria from Takeda, 
      Janssen, BMS, Sanofi, Magen, Oncopeptide, Karyopharm, Novartis, and Merck. JB 
      receives research funding from Abbvie, Amgen, Acetylon, Bluebird, BMS, Celgene, 
      Celularity, Constellation, CRISP Therapeutics, CURIS, EMD Sorono, Genentech, 
      Glenmark, Ichnos, Janssen, Kesios, Lilly, Novartis, Poseida, Sanofi, Takeda, 
      Teva, Vivolux. JB receives consultancy payments from Amgen, BioClinica, Bluebird, 
      BMS, Celgene, CRISPR Therapeutics, Janssen, Karyopharm, Kite Pharma, Legend, 
      Prothena, SecuraBio, and Servier. HCL reports consulting or advisory role for 
      Takeda, Celgene, Adaptive Biotechnologies, Amgen, GSK, Sanofi, and Janssen; 
      research funding from Takeda, Amgen, Daiichi Sankyo, Janssen, Celgene and GSK. KW 
      reports grants from Amgen, Celgene, Sanofi, Janssen (all to the institution), 
      honoraria and advisory board from Amgen, BMS, Celgene, Adaptive Biotech, Janssen, 
      GSK, Karyopharm, Roche, Sanofi, Takeda, and Oncopeptides. MT is an 
      advisor/consultant for Adaptive, BMS, Doximity, Elsevier, GRAIL/Ilumina, Syapse 
      Precision Medicine Council, Takeda, and UpToDate. He receives research funding 
      from AbbVie, Amgen, BMS, CRAB CTC, Denovo, GSK, Hoosier Research Network, 
      Janssen, Lilly, LynxBio, Strata Oncology, Takeda, and TG Therapeutics. MB has 
      received honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers 
      Squibb, and AbbVie; has served on the advisory boards for Janssen and GSK; has 
      received research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, 
      Bristol-Myers Squibb, and Mundipharma. JAZ reports consultancy or advisory role 
      for Celgene, BMS, Prothena, Janssen, Amgen, Takeda, Caelum Biosciences, Intellia 
      Therapeutics, Alnylam and Oncotherapeutics; institutional research funding from 
      Celgene and BMS. GC receives grant/research support from Celgene/BMS, Janssen, 
      and Takeda and honoraria from Amgen, BMS, Celgene, Janssen, Takeda, Roche, GSK, 
      Oncopeptides, and Sanofi. NP reports consulting or advisory role for Takeda, 
      Amgen, Celgene, and Janssen; speaker's bureau for Celgene; honoraria from Takeda, 
      Amgen, Celgene, Janssen, and The Binding Site; travel, accommodation, expenses 
      and research funding from Celgene, Janssen, Amgen, and Takeda. EF, AR, and MB are 
      or were employees of Xcenda, LLC at the time research was conducted; AC reports 
      grants and personal fees from Janssen, grants and personal fees from Celgene, 
      grants and personal fees from Novartis Pharmaceuticals, grants and personal fees 
      from Amgen, personal fees from Bristol Myers Squibb, grants from Pharmacyclics, 
      personal fees from Karyopharm, personal fees from Sanofi, grants and personal 
      fees from Seattle Genetics, personal fees from Oncopeptides, grants and personal 
      fees from Millenium/Takeda, personal fees from Antengene, personal fees from 
      GlaxoSmithKline, and personal fees from Secura Bio. No further conflicts are 
      reported by the authors.
EDAT- 2021/05/11 06:00
MHDA- 2021/08/21 06:00
PMCR- 2021/05/10
CRDT- 2021/05/10 12:28
PHST- 2021/01/08 00:00 [received]
PHST- 2021/03/22 00:00 [accepted]
PHST- 2021/05/11 06:00 [pubmed]
PHST- 2021/08/21 06:00 [medline]
PHST- 2021/05/10 12:28 [entrez]
PHST- 2021/05/10 00:00 [pmc-release]
AID - 10.1007/s00277-021-04534-8 [pii]
AID - 4534 [pii]
AID - 10.1007/s00277-021-04534-8 [doi]
PST - ppublish
SO  - Ann Hematol. 2021 Sep;100(9):2325-2337. doi: 10.1007/s00277-021-04534-8. Epub 
      2021 May 10.