Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14)

Introduction: The selective Bcl-2 inhibitor venetoclax has shown promising therapeutic potential in multiple myeloma, particularly in cases associated with t(11;14) IGH::CCND1 translocation. However, the efficacy of venetoclax in myeloma patients with the t(6;14) IGH::CCND3 translocation remains les...

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Main Authors: Andrea Ceglédi, Zoltán Csukly, Mónika Fekete, András Kozma, Zsuzsanna Szemlaky, Hajnalka Andrikovics, Gábor Mikala
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-11-01
Series:Pathology and Oncology Research
Subjects:
Online Access:https://www.por-journal.com/articles/10.3389/pore.2023.1611375/full
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author Andrea Ceglédi
Zoltán Csukly
Mónika Fekete
András Kozma
Zsuzsanna Szemlaky
Hajnalka Andrikovics
Gábor Mikala
author_facet Andrea Ceglédi
Zoltán Csukly
Mónika Fekete
András Kozma
Zsuzsanna Szemlaky
Hajnalka Andrikovics
Gábor Mikala
author_sort Andrea Ceglédi
collection DOAJ
description Introduction: The selective Bcl-2 inhibitor venetoclax has shown promising therapeutic potential in multiple myeloma, particularly in cases associated with t(11;14) IGH::CCND1 translocation. However, the efficacy of venetoclax in myeloma patients with the t(6;14) IGH::CCND3 translocation remains less investigated.Methods: In this study, we conducted a retrospective analysis to investigate the efficacy of venetoclax-based therapy in relapsed/refractory myeloma patients with t(6;14) translocation. The treatment courses of three patients, that included previous therapies and responses to venetoclax, were assessed. Clinical data, laboratory results, and adverse events were analyzed to evaluate treatment outcomes.Results: Our findings demonstrated remarkable therapeutic responses in three consecutive patients with t(6;14) translocation-associated myeloma who received venetoclax-based therapy. Patient 1, a lenalidomide-bortezomib-daratumumab and alkylator treatment refractory patient, achieved sustained stringent complete remission (sCR) after combining carfilzomib-dexamethasone with venetoclax, which was his best response ever. Similarly, Patient 2, refractory to frontline bortezomib-thalidomide-dexamethasone therapy, attained CR following a transition to bortezomib-dexamethason-venetoclax treatment. Patient 3, who was immunomodulatory (IMID)-intolerant, showed a highly favorable response to venetoclax-dexamethasone therapy after his first relapse following autologous stem cell transplantation. No significant adverse effects were observed in any of the patients.Discussion: Our study provides compelling preliminary evidence for the efficacy of venetoclax in t(6;14) translocation-associated myeloma. The outcomes observed in our patients suggest that venetoclax-based therapy holds substantial promise as an effective treatment option for this specific genetic subgroup. Furthermore, the similarities in treatment response between t(11;14) and t(6;14) translocation subgroups highlight the importance of personalized approaches targeting specific genetic abnormalities to optimize therapeutic outcomes.
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spelling doaj.art-f1942aab14334e64bc29fb8dba1905762024-04-04T16:20:44ZengFrontiers Media S.A.Pathology and Oncology Research1532-28072023-11-012910.3389/pore.2023.16113751611375Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14)Andrea Ceglédi0Zoltán Csukly1Mónika Fekete2András Kozma3Zsuzsanna Szemlaky4Hajnalka Andrikovics5Gábor Mikala6Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Budapest, HungaryDepartment of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Budapest, HungaryDepartment of Public Health, Semmelweis University, Budapest, HungaryLaboratory of Molecular Genetics, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Budapest, HungaryDepartment of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Budapest, HungaryLaboratory of Molecular Genetics, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Budapest, HungaryDepartment of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Budapest, HungaryIntroduction: The selective Bcl-2 inhibitor venetoclax has shown promising therapeutic potential in multiple myeloma, particularly in cases associated with t(11;14) IGH::CCND1 translocation. However, the efficacy of venetoclax in myeloma patients with the t(6;14) IGH::CCND3 translocation remains less investigated.Methods: In this study, we conducted a retrospective analysis to investigate the efficacy of venetoclax-based therapy in relapsed/refractory myeloma patients with t(6;14) translocation. The treatment courses of three patients, that included previous therapies and responses to venetoclax, were assessed. Clinical data, laboratory results, and adverse events were analyzed to evaluate treatment outcomes.Results: Our findings demonstrated remarkable therapeutic responses in three consecutive patients with t(6;14) translocation-associated myeloma who received venetoclax-based therapy. Patient 1, a lenalidomide-bortezomib-daratumumab and alkylator treatment refractory patient, achieved sustained stringent complete remission (sCR) after combining carfilzomib-dexamethasone with venetoclax, which was his best response ever. Similarly, Patient 2, refractory to frontline bortezomib-thalidomide-dexamethasone therapy, attained CR following a transition to bortezomib-dexamethason-venetoclax treatment. Patient 3, who was immunomodulatory (IMID)-intolerant, showed a highly favorable response to venetoclax-dexamethasone therapy after his first relapse following autologous stem cell transplantation. No significant adverse effects were observed in any of the patients.Discussion: Our study provides compelling preliminary evidence for the efficacy of venetoclax in t(6;14) translocation-associated myeloma. The outcomes observed in our patients suggest that venetoclax-based therapy holds substantial promise as an effective treatment option for this specific genetic subgroup. Furthermore, the similarities in treatment response between t(11;14) and t(6;14) translocation subgroups highlight the importance of personalized approaches targeting specific genetic abnormalities to optimize therapeutic outcomes.https://www.por-journal.com/articles/10.3389/pore.2023.1611375/fullmultiple myelomavenetoclaxtranslocation t(6;14)IGH::CCND3personalized therapy
spellingShingle Andrea Ceglédi
Zoltán Csukly
Mónika Fekete
András Kozma
Zsuzsanna Szemlaky
Hajnalka Andrikovics
Gábor Mikala
Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14)
Pathology and Oncology Research
multiple myeloma
venetoclax
translocation t(6;14)
IGH::CCND3
personalized therapy
title Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14)
title_full Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14)
title_fullStr Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14)
title_full_unstemmed Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14)
title_short Effective venetoclax-based treatment in relapsed/refractory multiple myeloma patients with translocation t(6;14)
title_sort effective venetoclax based treatment in relapsed refractory multiple myeloma patients with translocation t 6 14
topic multiple myeloma
venetoclax
translocation t(6;14)
IGH::CCND3
personalized therapy
url https://www.por-journal.com/articles/10.3389/pore.2023.1611375/full
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