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Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study

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,...

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Autores principales: Vitkon, Roy, Netanely, Dan, Levi, Shai, Ziv-Baran, Tomer, Ben-Yzak, Ronit, Katz, Ben-Zion, Benyamini, Noam, Trestman, Svetlana, Mittelman, Moshe, Cohen, Yael, Avivi, Irit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323447/
https://www.ncbi.nlm.nih.gov/pubmed/34377384
http://dx.doi.org/10.1177/20406207211035272
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author Vitkon, Roy
Netanely, Dan
Levi, Shai
Ziv-Baran, Tomer
Ben-Yzak, Ronit
Katz, Ben-Zion
Benyamini, Noam
Trestman, Svetlana
Mittelman, Moshe
Cohen, Yael
Avivi, Irit
author_facet Vitkon, Roy
Netanely, Dan
Levi, Shai
Ziv-Baran, Tomer
Ben-Yzak, Ronit
Katz, Ben-Zion
Benyamini, Noam
Trestman, Svetlana
Mittelman, Moshe
Cohen, Yael
Avivi, Irit
author_sort Vitkon, Roy
collection PubMed
description 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.
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spelling pubmed-83234472021-08-09 Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study Vitkon, Roy Netanely, Dan Levi, Shai Ziv-Baran, Tomer Ben-Yzak, Ronit Katz, Ben-Zion Benyamini, Noam Trestman, Svetlana Mittelman, Moshe Cohen, Yael Avivi, Irit Ther Adv Hematol Original Research 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. SAGE Publications 2021-07-28 /pmc/articles/PMC8323447/ /pubmed/34377384 http://dx.doi.org/10.1177/20406207211035272 Text en © The Author(s), 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Vitkon, Roy
Netanely, Dan
Levi, Shai
Ziv-Baran, Tomer
Ben-Yzak, Ronit
Katz, Ben-Zion
Benyamini, Noam
Trestman, Svetlana
Mittelman, Moshe
Cohen, Yael
Avivi, Irit
Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study
title Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study
title_full Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study
title_fullStr Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study
title_full_unstemmed Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study
title_short Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study
title_sort daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323447/
https://www.ncbi.nlm.nih.gov/pubmed/34377384
http://dx.doi.org/10.1177/20406207211035272
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