PMID- 32409106
OWN - NLM
STAT- MEDLINE
DCOM- 20210907
LR  - 20210907
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 20
IP  - 9
DP  - 2020 Sep
TI  - Safety Analysis of Five Randomized Controlled Studies of Daratumumab in Patients 
      With Multiple Myeloma.
PG  - e579-e589
LID - S2152-2650(20)30182-8 [pii]
LID - 10.1016/j.clml.2020.04.004 [doi]
AB  - BACKGROUND: Multiple studies have demonstrated the efficacy and safety of 
      daratumumab for relapsed/refractory multiple myeloma (MM) and primary treatment 
      for transplant-eligible and -ineligible patients. MATERIALS AND METHODS: We 
      conducted an integrated safety analysis to characterize the frequency, severity, 
      natural history, and outcomes of adverse events (AEs) with daratumumab versus 
      comparators. Data were pooled from 5 completed phase III randomized controlled 
      studies that had included 1798 daratumumab-treated and 1797 comparator-treated 
      patients with MM as a first line in both transplant-eligible and 
      transplant-ineligible patients and for relapsed/refractory disease. Safety 
      analyses included reporting of AEs using crude and exposure-adjusted incidence 
      rates. RESULTS: The median follow-up duration was 16.84 months (range, 7.4-28 
      months) for both daratumumab-treated and comparator-treated patients. 
      Discontinuation for any reason occurred less often with daratumumab (22% vs. 
      33.9%), although discontinuation because of AEs occurred at similar rates (25% 
      vs. 26%) as did deaths owing to AEs (2.25% vs. 1.84%). When adjusted for 
      exposure, neutropenia, lymphopenia, diarrhea, fatigue, dyspnea, pneumonia, and 
      hypertension were the only common grade 3/4 AEs reported more often with 
      daratumumab than with the comparators. The prevalence of common grade 3/4 AEs 
      with daratumumab were < 7% apart from neutropenia, lymphopenia, and pneumonia 
      (45.9% vs. 32.3%, 13% vs. 7.5%, and 10.6% vs. 7.2%, respectively). Grade 3/4 
      daratumumab infusion-related reactions happened in 3.8% of patients. The majority 
      of infusion-related reactions occurred after the first infusion. CONCLUSIONS: 
      These results from an integrated analysis support a favorable benefit/risk 
      profile of daratumumab in patients with MM.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Al Hadidi, Samer
AU  - Al Hadidi S
AD  - Section of Hematology and Oncology, Baylor College of Medicine, Houston, TX. 
      Electronic address: hadidi@bcm.edu.
FAU - Miller-Chism, Courtney Nicole
AU  - Miller-Chism CN
AD  - Section of Hematology and Oncology, Baylor College of Medicine, Houston, TX.
FAU - Kamble, Rammurti
AU  - Kamble R
AD  - Section of Hematology and Oncology, Baylor College of Medicine, Houston, TX.
FAU - Mims, Martha
AU  - Mims M
AD  - Section of Hematology and Oncology, Baylor College of Medicine, Houston, TX.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20200420
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 0 (Antibodies, Monoclonal)
RN  - 4Z63YK6E0E (daratumumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/pharmacology/*therapeutic use
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy
OTO - NOTNLM
OT  - Adverse events
OT  - Benefit/risk profile
OT  - Daratumumab
OT  - Exposure-adjusted incidence rate
OT  - Pooled analysis
EDAT- 2020/05/16 06:00
MHDA- 2021/09/08 06:00
CRDT- 2020/05/16 06:00
PHST- 2020/02/13 00:00 [received]
PHST- 2020/04/06 00:00 [revised]
PHST- 2020/04/09 00:00 [accepted]
PHST- 2020/05/16 06:00 [pubmed]
PHST- 2021/09/08 06:00 [medline]
PHST- 2020/05/16 06:00 [entrez]
AID - S2152-2650(20)30182-8 [pii]
AID - 10.1016/j.clml.2020.04.004 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2020 Sep;20(9):e579-e589. doi: 
      10.1016/j.clml.2020.04.004. Epub 2020 Apr 20.