PMID- 38052042
OWN - NLM
STAT- MEDLINE
DCOM- 20240101
LR  - 20240115
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 8
IP  - 1
DP  - 2024 Jan 9
TI  - Teclistamab impairs humoral immunity in patients with heavily pretreated myeloma: 
      importance of immunoglobulin supplementation.
PG  - 194-206
LID - 10.1182/bloodadvances.2023011658 [doi]
AB  - Teclistamab and other B-cell maturation antigen (BCMA)-targeting bispecific 
      antibodies (BsAbs) have substantial activity in patients with heavily pretreated 
      multiple myeloma (MM) but are associated with a high rate of infections. BCMA is 
      also expressed on normal plasma cells and mature B cells, which are essential for 
      the generation of a humoral immune response. The aim of this study was to improve 
      the understanding of the impact of BCMA-targeting BsAbs on humoral immunity. The 
      impact of teclistamab on polyclonal immunoglobulins and B cell counts was 
      evaluated in patients with MM who received once-weekly teclistamab 1.5 mg/kg 
      subcutaneously. Vaccination responses were assessed in a subset of patients. 
      Teclistamabinduced rapid depletion of peripheral blood B cells in patients with 
      MM and eliminated normal plasma cells in ex vivo assays. In addition, teclistamab 
      reduced the levels of polyclonal immunoglobulins (immunoglobulin G [IgG], IgA, 
      IgE, and IgM), without recovery over time while receiving teclistamab therapy. 
      Furthermore, response to vaccines against Streptococcus pneumoniae, Haemophilus 
      influenzae type B, and severe acute respiratory syndrome coronavirus 2 was 
      severely impaired in patients treated with teclistamab compared with vaccination 
      responses observed in patients with newly diagnosed MM or relapsed/refractory MM. 
      Intravenous immunoglobulin (IVIG) use was associated with a significantly lower 
      risk of serious infections among patients treated with teclistamab (cumulative 
      incidence of infections at 6 months: 5.3% with IVIG vs 54.8% with observation 
      only [P < .001]). In conclusion, our data show severe defects in humoral immunity 
      induced by teclistamab, the impact of which can be mitigated by the use of 
      immunoglobulin supplementation. This trial was registered at 
      www.ClinicalTrials.gov as #NCT04557098.
CI  - (c) 2024 by The American Society of Hematology. Licensed under Creative Commons 
      Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), 
      permitting only noncommercial, nonderivative use with attribution. All other 
      rights reserved.
FAU - Frerichs, Kristine A
AU  - Frerichs KA
AD  - Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, 
      Amsterdam, The Netherlands.
AD  - Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The 
      Netherlands.
FAU - Verkleij, Christie P M
AU  - Verkleij CPM
AD  - Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, 
      Amsterdam, The Netherlands.
AD  - Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The 
      Netherlands.
FAU - Mateos, Maria Victoria
AU  - Mateos MV
AUID- ORCID: 0000-0003-2390-1218
AD  - University Hospital of Salamanca/IBSAL/CIC/CIBERONC, Salamanca, Spain.
FAU - Martin, Thomas G
AU  - Martin TG
AD  - University of California, San Francisco, San Francisco, CA.
FAU - Rodriguez, Cesar
AU  - Rodriguez C
AD  - Icahn School of Medicine at Mount Sinai, New York, NY.
FAU - Nooka, Ajay
AU  - Nooka A
AD  - Winship Cancer Institute, Emory University, Atlanta, GA.
FAU - Banerjee, Arnob
AU  - Banerjee A
AD  - Janssen Research & Development, Spring House, PA.
FAU - Chastain, Katherine
AU  - Chastain K
AD  - Janssen Research & Development, Spring House, PA.
FAU - Perales-Puchalt, Alfredo
AU  - Perales-Puchalt A
AUID- ORCID: 0000-0003-4904-5050
AD  - Janssen Research & Development, Spring House, PA.
FAU - Stephenson, Tara
AU  - Stephenson T
AD  - Janssen Research & Development, Spring House, PA.
FAU - Uhlar, Clarissa
AU  - Uhlar C
AD  - Janssen Research & Development, Spring House, PA.
FAU - Kobos, Rachel
AU  - Kobos R
AD  - Janssen Research & Development, Spring House, PA.
FAU - van der Holt, Bronno
AU  - van der Holt B
AUID- ORCID: 0000-0001-6414-2671
AD  - HOVON Foundation, Rotterdam, The Netherlands.
AD  - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The 
      Netherlands.
FAU - Kruyswijk, Sandy
AU  - Kruyswijk S
AD  - Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, 
      Amsterdam, The Netherlands.
AD  - Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The 
      Netherlands.
FAU - Kuipers, Maria T
AU  - Kuipers MT
AD  - Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, 
      Amsterdam, The Netherlands.
AD  - Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The 
      Netherlands.
FAU - Groen, Kaz
AU  - Groen K
AD  - Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, 
      Amsterdam, The Netherlands.
AD  - Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The 
      Netherlands.
FAU - Vishwamitra, Deeksha
AU  - Vishwamitra D
AD  - Janssen Research & Development, Spring House, PA.
FAU - Skerget, Sheri
AU  - Skerget S
AD  - Janssen Research & Development, Spring House, PA.
FAU - Cortes-Selva, Diana
AU  - Cortes-Selva D
AD  - Janssen Research & Development, Spring House, PA.
FAU - Doyle, Margaret
AU  - Doyle M
AD  - Janssen Sciences, Cork, Ireland.
FAU - Zaaijer, Hans L
AU  - Zaaijer HL
AD  - Department of Medical Microbiology, Amsterdam UMC location, Academic Medical 
      Center, Amsterdam, The Netherlands.
FAU - Zweegman, Sonja
AU  - Zweegman S
AUID- ORCID: 0000-0002-5011-1820
AD  - Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, 
      Amsterdam, The Netherlands.
AD  - Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The 
      Netherlands.
FAU - Verona, Raluca I
AU  - Verona RI
AUID- ORCID: 0000-0003-0044-4341
AD  - Janssen Research & Development, Spring House, PA.
FAU - van de Donk, Niels W C J
AU  - van de Donk NWCJ
AD  - Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, 
      Amsterdam, The Netherlands.
AD  - Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The 
      Netherlands.
LA  - eng
SI  - ClinicalTrials.gov/NCT04557098
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Antibodies, Bispecific)
RN  - 0 (B-Cell Maturation Antigen)
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Humans
MH  - *Multiple Myeloma/drug therapy
MH  - Immunity, Humoral
MH  - Immunoglobulins, Intravenous/therapeutic use
MH  - *Antibodies, Bispecific/therapeutic use
MH  - B-Cell Maturation Antigen/therapeutic use
MH  - *Antineoplastic Agents/therapeutic use
MH  - Dietary Supplements
PMC - PMC10787247
COIS- Conflict-of-interest disclosure: M.V.M. reports honoraria from, and membership on 
      a board of directors/advisory committee for, Amgen, Bristol Myers Squibb/Celgene, 
      GlaxoSmithKline, Janssen Cilag, Pfizer, Sanofi, and Takeda; is a speaker bureau 
      member for Janssen Cilag; and is a board of directors/advisory committee member 
      for Oncopeptides. T.G.M. reports research funding (institutional) from Amgen, 
      Janssen, Sanofi, and Seattle Genetics; and consultancy for GlaxoSmithKline and 
      Roche. C.R. reports personal fees from Amgen, Bristol Myers Squibb, and Takeda. 
      A.N. has served on advisory boards of, and received honorarium from, Adaptive 
      Biotechnologies, Amgen, BeyondSpring, Bristol Myers Squibb, GlaxoSmithKline, 
      Janssen, Karyopharm, Oncopeptides, Pfizer, Sanofi, Secura Bio, and Takeda; has 
      received grant/research support (institutional) from Aduro Biotech, Amgen, Arch 
      Oncology, Bristol Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Karyopharm, 
      Kite Pharma, Pfizer, and Takeda; and received grant/research support for 
      investigator-initiated studies from Amgen, GlaxoSmithKline, Janssen, Merck, and 
      Takeda. A.B. is an employee of Janssen and is a stockholder in Janssen. K.C. is 
      an employee of Janssen and is a stockholder in Janssen. A.P.-P. is an employee of 
      Janssen and is a stockholder in Janssen. T.S. is an employee of Janssen and is a 
      stockholder in Janssen. C.U. is an employee of Janssen and is a stockholder in 
      Janssen. R.K. is an employee of Janssen and is a stockholder in Janssen. B.v.d.H. 
      reports honoraria for data safety monitoring board membership from the 
      Intergroupe Francophone du Myelome. S.K. serves on advisory boards for Janssen 
      Pharmaceuticals. D.V. is an employee of Janssen and is a stockholder in Janssen. 
      S.S. is an employee of Janssen and is a stockholder in Janssen. D.C.-S. is an 
      employee of Janssen and is a stockholder in Janssen. M.D. is an employee of 
      Janssen and is a stockholder in Janssen. S.Z. has received research funding from 
      Celgene, Takeda, and Janssen; and serves on advisory boards for Janssen, Takeda, 
      Bristol Myers Squibb, Oncopeptides, and Sanofi, all paid to institution. R.I.V. 
      is an employee of Janssen and is a stockholder in Janssen. N.W.C.J.v.d.D. has 
      received research support from Janssen Pharmaceuticals, Amgen, Celgene, Novartis, 
      Cellectis, and Bristol Myers Squibb; and serves on advisory boards for Janssen 
      Pharmaceuticals, AMGEN, Celgene, Bristol Myers Squibb, Takeda, Roche, Novartis, 
      Bayer, Adaptive, Pfizer, AbbVie, and Servier, all paid to institution. The 
      remaining authors declare no competing financial interest.
EDAT- 2023/12/06 03:42
MHDA- 2024/01/02 11:46
PMCR- 2023/12/07
CRDT- 2023/12/05 17:09
PHST- 2023/11/17 00:00 [accepted]
PHST- 2023/09/11 00:00 [received]
PHST- 2024/01/02 11:46 [medline]
PHST- 2023/12/06 03:42 [pubmed]
PHST- 2023/12/05 17:09 [entrez]
PHST- 2023/12/07 00:00 [pmc-release]
AID - 506506 [pii]
AID - 10.1182/bloodadvances.2023011658 [doi]
PST - ppublish
SO  - Blood Adv. 2024 Jan 9;8(1):194-206. doi: 10.1182/bloodadvances.2023011658.