Teclistamab impairs humoral immunity in patients with heavily pretreated myeloma: importance of immunoglobulin supplementation

Kristine A. Frerichs, Christie P.M. Verkleij, Maria Victoria Mateos, Thomas G. Martin, Cesar Rodriguez, Ajay Nooka, Arnob Banerjee, Katherine Chastain, Alfredo Perales-Puchalt, Tara Stephenson, Clarissa Uhlar, Rachel Kobos, Bronno Van Der Holt, Sandy Kruyswijk, Maria T. Kuipers, Kaz Groen, Deeksha Vishwamitra, Sheri Skerget, Diana Cortes-Selva, Margaret DoyleHans L. Zaaijer, Sonja Zweegman, Raluca I. Verona, Niels W.C.J. Van De Donk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
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Abstract

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 onceweekly 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.

Original languageEnglish
Pages (from-to)194-206
Number of pages13
JournalBlood Advances
Volume8
Issue number1
DOIs
Publication statusPublished - 9 Jan 2024

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© 2024 by The American Society of Hematology.

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