PMID- 34377384
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220425
IS  - 2040-6207 (Print)
IS  - 2040-6215 (Electronic)
IS  - 2040-6207 (Linking)
VI  - 12
DP  - 2021
TI  - Daratumumab in combination with proteasome inhibitors, rapidly decreases 
      polyclonal immunoglobulins and increases infection risk among relapsed multiple 
      myeloma patients: a single center retrospective study.
PG  - 20406207211035272
LID - 10.1177/20406207211035272 [doi]
LID - 20406207211035272
AB  - BACKGROUND: Daratumumab (Dara) is generally well tolerated, but is associated 
      with increased risk of infection. METHODS: We investigated hypogammaglobinemia 
      occurrence in different Dara-based regimens. Multiple myeloma (MM) patients were 
      treated with ⩾2 cycles of Dara-based therapy during 2016-2020, mainly for 
      relapsed/refractory disease. Data on patient characteristics, treatment regimens, 
      polyclonal IgG (poly-IgG) and uninvolved free light chain (Un-FLC) levels during 
      treatment, as well as predictors for hypogammaglobinemia and predictors for 
      infections, were evaluated retrospectively. RESULTS: A total of 84 patients, 
      median age 67.2 years, were included. Dara, mainly as ⩾2 line therapy (88.1%, 
      n = 74), was combined with immunomodulating drugs (IMiDs) (53%), proteasome 
      inhibitors (PIs) (15%), IMiDs-PIs (11%), or dexamethasone only (21%). Median 
      treatment duration was 13 months. Median Poly-IgG levels at 0, 2, and 4 months 
      were 7.1 g/l, 4.5 g/l, and 4 g/l, respectively, and remained low throughout 
      treatment. Lower poly-IgG pre-Dara (p = 0.001) and Dara-PIs (+/-IMiDs) regimen were 
      associated with lower poly-IgG levels at 4 months (p = 0.03). Only patients 
      treated with Dara monotherapy had partial immune reconstitution, reflected by 
      resumption of IgM levels. Most (85%) patients developed ⩾1 infections, mostly 
      grade 1-2 respiratory (76%). A lower poly-IgG level post Dara (RR = 1.137 
      p = 0.026) predicted increased risk of any infection. Intravenous immunoglobulin 
      (IVIG) was associated with a significant decrease in all infections. CONCLUSION: 
      Relapsed MM patients treated with Dara, often experience persistent 
      hypogammaglobinemia, irrespective of responsiveness to treatment. Infections, 
      especially respiratory, are frequent and apparently related to low Poly-IgG 
      levels. IVIG should be considered for reducing infections in these patients.
CI  - (c) The Author(s), 2021.
FAU - Vitkon, Roy
AU  - Vitkon R
AUID- ORCID: 0000-0001-9843-8817
AD  - Department of Hematology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street., 
      Tel Aviv, 64239, Israel.
FAU - Netanely, Dan
AU  - Netanely D
AD  - Department of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
FAU - Levi, Shai
AU  - Levi S
AD  - Department of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
FAU - Ziv-Baran, Tomer
AU  - Ziv-Baran T
AD  - School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel 
      Aviv, Israel.
FAU - Ben-Yzak, Ronit
AU  - Ben-Yzak R
AD  - The Hematology Laboratory, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
FAU - Katz, Ben-Zion
AU  - Katz BZ
AD  - The Hematology Laboratory, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
FAU - Benyamini, Noam
AU  - Benyamini N
AD  - Department of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
FAU - Trestman, Svetlana
AU  - Trestman S
AD  - Department of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
FAU - Mittelman, Moshe
AU  - Mittelman M
AD  - Department of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
FAU - Cohen, Yael
AU  - Cohen Y
AD  - Department of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
FAU - Avivi, Irit
AU  - Avivi I
AD  - Department of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
LA  - eng
PT  - Journal Article
DEP - 20210728
PL  - England
TA  - Ther Adv Hematol
JT  - Therapeutic advances in hematology
JID - 101549589
PMC - PMC8323447
OTO - NOTNLM
OT  - IVIG
OT  - daratumumab
OT  - hypogammaglobinemia
OT  - infections
OT  - multiple myeloma
COIS- Conflict of interest statement: The authors declare that there is no conflict of 
      interest.
EDAT- 2021/08/12 06:00
MHDA- 2021/08/12 06:01
PMCR- 2021/07/28
CRDT- 2021/08/11 06:38
PHST- 2021/05/02 00:00 [received]
PHST- 2021/07/08 00:00 [accepted]
PHST- 2021/08/11 06:38 [entrez]
PHST- 2021/08/12 06:00 [pubmed]
PHST- 2021/08/12 06:01 [medline]
PHST- 2021/07/28 00:00 [pmc-release]
AID - 10.1177_20406207211035272 [pii]
AID - 10.1177/20406207211035272 [doi]
PST - epublish
SO  - Ther Adv Hematol. 2021 Jul 28;12:20406207211035272. doi: 
      10.1177/20406207211035272. eCollection 2021.