Risk of infections associated with the use of bispecific antibodies in multiple myeloma: a pooled analysis
Open accessAbstract
The use of bispecific antibodies (BsAbs) in the treatment of relapsed/refractory multiple myeloma (MM) is showing early promising overall response rates in heavily pretreated patients. Infectious complications related to the use of BsAbs are not well described. We conducted a pooled analysis that included all single-agent BsAbs used in MM with no prior use of different BsAbs. A total of 1185 patients with MM were treated with a BsAb in the studied period (71.6% of the patients treated with an agent targeting B-cell maturation antigen (BCMA). Pooled median follow-up was short at 6.1 months (7.5 vs 5.2 months for BCMA vs non-BCMA BsAbs, respectively). Adverse events of interest included all grade neutropenia in 38.6%, all grade infections in 50% (n = 542/1083), all grade cytokine release syndrome in 59.6% (n = 706/1185), grade III/IV neutropenia in 34.8% (n = 372/1068), grade III/IV infections in 24.5% (n = 272/1110), grade III/IV pneumonia in 10% (n = 52.4/506), and grade III/IV coronavirus disease 2019 in 11.4% (n = 45.4/395) of the patients. Non-BCMA–targeted BsAbs were associated with lower grade III/IV neutropenia (25.3% vs 39.2%) and lower grade III/IV infections (11.9% vs 30%) when compared with BCMA-targeted BsAbs. Hypogammaglobulinemia was reported in 4 studies, with a prevalence of 75.3% (n = 256/340) of the patients, with IV immunoglobulin used in 48% (n = 123/256) of them. Death was reported in 110 patients, of which 28 (25.5%) were reported to be secondary to infections. Certain precautions should be used when using BsAbs to mitigate the risk and/or identify and treat infections promptly.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inhibiting BCMA signaling, which is critical for the survival and proliferation of plasma cells, may worsen the pre-existing myeloma-induced immunosupression.
“Inhibiting BCMA signaling, which is critical for the survival and proliferation of plasma cells, may worsen the pre-existing myeloma-induced immunosupression31,32,34.”
From Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results (2023) · cites this paper as [31]
The Discussion (page unavailable) says BCMA contributes to immunoglobulin formation and immunity, and reports more infections with BCMA-targeting than non-BCMA bispecific antibodies. It does not say BCMA signaling is critical for plasma-cell survival and proliferation; it attributes patients’ pre-existing immunosuppression chiefly to prior therapies rather than myeloma itself. (LLM, conf=0.85)
Experimental — accuracy not yet measuredBCMA-targeted T-cell-redirecting therapies have been linked to a heightened susceptibility to infectious complications due to their mechanism of action.
“BCMA-targeted T-cell-redirecting therapies have been linked to a heightened susceptibility to infectious complications due to their mechanism of action30–33.”
From Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results (2023) · cites this paper as [31]
The Results report more severe infections with BCMA-targeting than non-BCMA bispecific antibodies, and the Discussion describes treatment-related immune changes that increase infection risk. However, the Discussion says infections may be related to the underlying myeloma, prior therapies, and/or the antibodies’ mechanism of action; it does not establish that the mechanism is the cause. Page numbers were not supplied in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Teclistamab in Relapsed or Refractory Multiple Myeloma
Moreau, P., Garfall, A. L., van de Donk, N. W. C. J., Nahi, H., San-Miguel, J. F., Oriol, A., Nooka, A. K., Martin, T., Rosinol, L., Chari, A., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2203478 · Cited by 1,269 · cited 2× · see citing works
“5% of the patients (n = 123/165).(4) ABBV-383 was associated with hypogammaglobulinemia in 14% of the patients (n = 17/124).”
Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma
Chari, A., Minnema, M. C., Berdeja, J. G., Oriol, A., van de Donk, N. W. C. J., Rodríguez-Otero, P., Askari, E., Mateos, M.-V., Costa, L. J., Caers, J., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2204591 · Cited by 744 · see citing works
Anti–B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma
Topp, M. S., Duell, J., Zugmaier, G., Attal, M., Moreau, P., Langer, C., Krönke, J., Facon, T., Salnikov, A. V., Lesley, R., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.02657 · Cited by 304 · see citing works
Flagged first, then by citations
Research works printed but not linked: 8
- [1]Blimark C Holmberg E Mellqvist UH Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients Haematologica 100 1 2015 107 113 25344526 PMC4281323
- [2]Cowan AJ Allen C Barac A Global burden of multiple myeloma: a systematic analysis for the global burden of disease study 2016 JAMA Oncol 4 9 2018 1221 1227 29800065 PMC6143021
- [3]Longhitano AP Slavin MA Harrison SJ Teh BW Bispecific antibody therapy, its use and risks for infection: bridging the knowledge gap Blood Rev 49 2021 100810 33676765
- [10]D'Souza A Shah N Rodriguez C A phase I first-in-human study of ABBV-383, a B-cell maturation antigen × CD3 bispecific t-cell redirecting antibody, in patients with relapsed/refractory multiple myeloma J Clin Oncol 40 31 2022 3576 3586 36029527 PMC9622641
- [15]Lancman G Sastow DL Cho HJ Bispecific antibodies in multiple myeloma: present and future Blood Cancer Discov 2 5 2021 423 433 34661161 PMC8510808
- [16]Kleber M Ntanasis-Stathopoulos I Terpos E BCMA in multiple myeloma-a promising key to therapy J Clin Med 10 18 2021 4088 34575199 PMC8472544
- [17]Elkins K Zheng B Go M FcRL5 as a target of antibody-drug conjugates for the treatment of multiple myeloma Mol Cancer Ther 11 10 2012 2222 2232 22807577
- [20]Philipp N Kazerani M Nicholls A T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals Blood 140 10 2022 1104 1118 35878001
Cited by
Sorted by citations
Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results
Lesokhin, A. M., Tomasson, M. H., Arnulf, B., Bahlis, N. J., Miles Prince, H., Niesvizky, R., Rodrίguez-Otero, P., Martinez-Lopez, J., Koehne, G., Touzeau, C., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02528-9 · Cited by 664 · see citing works
- Authors
- Mazahreh, F., Mazahreh, L., Schinke, C., Thanendrarajan, S., Zangari, M., Shaughnessy, J. D., Zhan, F., van Rhee, F., & Al Hadidi, S.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Hashemite University (JO)
- 3Myeloma Institute, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR
- ORCID
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2023-06-30
- Volume
- 7
- Issue
- 13
- Pages
- 3069-3074
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- PMC
- PMC10331406
- OpenAlex
- W4322730657
- Cited by
- 142
- References
- 3
- Citations by year
- 2026: 36 · 2025: 32 · 2024: 46 · 2023: 26 · 2013: 1
- FWCI
- 28.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Blood Advances (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Keywords
- bispecific antibodies, multiple myeloma, relapsed/refractory multiple myeloma, infection, neutropenia, cytokine release syndrome, hypogammaglobulinemia, pneumonia, COVID-19 pandemic, immunoglobulin therapy, infection-related mortality
- MeSH terms
- COVID-19, Humans, Multiple Myeloma, Neutropenia, Antibodies, Bispecific, Neoplasms, Plasma Cell
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
