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Hematology

Kinetics of Humoral Immunodeficiency With Bispecific Antibody Therapy in Relapsed Refractory Multiple Myeloma

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To identify the key insights or developments described in this article

1 Credit CME

JAMA Network Open

Published Online: October 28, 2022

Research Letter

Article Information and Disclosures

Lindsay R. Hammons, MD¹;

Aniko Szabo, PhD¹;

Abhishek Janardan, BS¹;

Binod Dhakal, MD, MS¹;

Saurabh Chhabra, MD, MS¹;

Anita D’Souza, MD, MS¹;

Meera Mohan, MD, MS¹

Author Affiliations

¹Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee

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Bispecific antibodies (bsAb) targeting novel antigens are a promising class of therapeutics for relapsed refractory multiple myeloma (RRMM).¹^,2 Although hypogammaglobulinemia is expected due to plasma cell depletion,³^- 5 little is known regarding the degree of humoral immunodeficiency and infectious complications with bsAb. We report on the kinetics of humoral deficiency among patients with RRMM treated with bsAb, the infectious complications, and response to COVID-19 immunization.

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Article Information

Accepted for Publication: September 9, 2022.

Published: October 28, 2022. doi:10.1001/jamanetworkopen.2022.38961

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Hammons LR et al. JAMA Network Open.

Corresponding Author: Meera Mohan, MD, MS, Division of Hematology and Oncology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226 (memohan@mcw.edu).

Author Contributions: Drs Hammons and Mohan had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Dhakal, Chhabra, D’Souza, Mohan.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Szabo, Dhakal, D’Souza, Mohan.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Hammons, Szabo.

Administrative, technical, or material support: Janardan.

Supervision: Dhakal, Mohan.

Conflict of Interest Disclosures: Dr Dhakal reported consulting for Janssen Pharmaceuticals and Karyopharm Therapeutics Inc and serving on the advisory boards of Sanofi, Amgen Inc, Natera, and Arcellx, Inc, outside the submitted work. Dr D’Souza reported serving on clinical trial advisory boards for Janssen Pharmaceuticals and Prothena Corporation PLC, performing clinical trials for Teneobio, Inc, Regeneron Pharmaceuticals, Inc, and Caelum, and serving on the advisory boards of Bristol-Myers Squibb Company, Caelum, and Pfizer Inc outside the submitted work. Dr Mohan reported receiving institutional research funding from Takeda Pharmaceutical Company Limited, Novartis AG, Celgene/Bristol-Myers Squibb Company, and GSK PLC outside the submitted work. No other disclosures were reported.

Disclaimer: All information and materials in the manuscript are original.

Meeting Presentation: These findings were presented in part at the Annual Meeting of the American Society of Clinical Oncology; June 4, 2022; Chicago, Illinois.

References

Lancman G , Richter J , Chari A . Bispecifics, trispecifics, and other novel immune treatments in myeloma. Hematology Am Soc Hematol Educ Program. 2020;2020(1):264-271. doi:10.1182/hematology.2020000110 PubMed Google Scholar Crossref

Usmani SZ , Garfall AL , van de Donk NWCJ , et al. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet. 2021;398(10301):665-674. doi:10.1016/S0140-6736(21)01338-6 PubMed Google Scholar Crossref

Kambhampati S , Sheng Y , Huang CY , et al. Infectious complications in patients with relapsed refractory multiple myeloma after BCMA CAR T-cell therapy. Blood Adv. 2022;6(7):2045-2054. doi:10.1182/bloodadvances.2020004079 PubMed Google Scholar Crossref

Mohan M , Nagavally S , Dhakal B , et al. Risk of infections with B-cell maturation antigen-directed immunotherapy in multiple myeloma. Blood Adv. 2022;6(8):2466-2470. doi:10.1182/bloodadvances.2021006178 PubMed Google Scholar Crossref

Wang Y , Li C , Xia J , et al. Humoral immune reconstitution after anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. Blood Adv. 2021;5(23):5290-5299. doi:10.1182/bloodadvances.2021004603 PubMed Google Scholar Crossref

Lee DW , Santomasso BD , Locke FL , et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758 PubMed Google Scholar Crossref

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Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
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1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

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