Polyclonal immunoglobulin recovery in patients with newly diagnosed myeloma receiving maintenance therapy after autologous haematopoietic stem cell transplantation with either carfilzomib, lenalidomide and dexamethasone or lenalidomide alone: Subanalysis of the randomized phase 3 ATLAS trial
Summary Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B‐c...
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| Veröffentlicht in: | British journal of haematology 2023-12, Vol.203 (5), p.792-802 |
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| creator | Kubicki, Tadeusz Dytfeld, Dominik Wróbel, Tomasz Jamroziak, Krzysztof Robak, Paweł Czyż, Jarosław Tyczyńska, Agata Druzd‐Sitek, Agnieszka Giannopoulos, Krzysztof Szczepaniak, Tomasz Łojko‐Dankowska, Anna Matuszak, Magdalena Gil, Lidia Puła, Bartosz Rybka, Justyna Majcherek, Maciej Usnarska‐Zubkiewicz, Lidia Szukalski, Łukasz Zaucha, Jan Maciej Mikulski, Damian Czabak, Olga Lahoud, Oscar B. Stefka, Andrew Derman, Benjamin A. Jakubowiak, Andrzej J. |
| description | Summary
Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B‐cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance. In the KRd arm, standard‐risk patients with minimal residual disease negativity after six cycles de‐escalated to R alone after cycle 8. One year from the initiation of maintenance at least partial recovery of polyclonal immunoglobulin was observed in more patients on the R arm (58/66, p |
| doi_str_mv | 10.1111/bjh.19097 |
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Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B‐cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance. In the KRd arm, standard‐risk patients with minimal residual disease negativity after six cycles de‐escalated to R alone after cycle 8. One year from the initiation of maintenance at least partial recovery of polyclonal immunoglobulin was observed in more patients on the R arm (58/66, p < 0.001) and in those who de‐escalated from KRd to R (27/38, p < 0.001) compared to the KRd arm (9/36). In patients who switched from KRd to R, the concentrations of uninvolved immunoglobulin and the number of B‐cell unique sequences increased over time, approaching values observed in the R arm. There were no differences in progression‐free survival between the patients with at least partial immunoglobulin recovery and the remaining population. Our analysis indicates that patients receiving continuous therapy after ASCT experience prolonged immunoparesis, limiting prognostic significance of polyclonal immunoglobulin recovery in this setting.
In multiple myeloma, recovery from immunoparesis after autologous haematopoietic stem cell transplantation has historically been associated with improved outcomes. However, these findings have not been validated among patients uniformly treated with modern maintenance. This subanalysis of the ATLAS trial, which randomized patients to receive maintenance with carfilzomib, lenalidomide and dexamethasone, or lenalidomide alone, does not confirm the prognostic significance of polyclonal immunoglobulin recovery. The design of the ATLAS trial, including the de‐escalation of therapy in a subset of patients initially treated with carfilzomib, lenalidomide and dexamethasone, allowed for the analysis of the effects of different treatment regimens on humoral immunity.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/bjh.19097</identifier><identifier>PMID: 37691005</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; carfilzomib ; Dexamethasone ; Dexamethasone - therapeutic use ; Hematology ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hematopoietic stem cells ; Humans ; Immunoglobulins ; immunoparesis ; Immunotherapy ; lenalidomide ; Lenalidomide - therapeutic use ; maintenance ; Minimal residual disease ; Multiple myeloma ; Multiple Myeloma - drug therapy ; myeloma ; Stem cell transplantation ; Stem cells ; Targeted cancer therapy ; Transplantation, Autologous ; Transplants & implants</subject><ispartof>British journal of haematology, 2023-12, Vol.203 (5), p.792-802</ispartof><rights>2023 The Authors. published by British Society for Haematology and John Wiley & Sons Ltd.</rights><rights>2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). 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Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B‐cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance. In the KRd arm, standard‐risk patients with minimal residual disease negativity after six cycles de‐escalated to R alone after cycle 8. One year from the initiation of maintenance at least partial recovery of polyclonal immunoglobulin was observed in more patients on the R arm (58/66, p < 0.001) and in those who de‐escalated from KRd to R (27/38, p < 0.001) compared to the KRd arm (9/36). In patients who switched from KRd to R, the concentrations of uninvolved immunoglobulin and the number of B‐cell unique sequences increased over time, approaching values observed in the R arm. There were no differences in progression‐free survival between the patients with at least partial immunoglobulin recovery and the remaining population. Our analysis indicates that patients receiving continuous therapy after ASCT experience prolonged immunoparesis, limiting prognostic significance of polyclonal immunoglobulin recovery in this setting.
In multiple myeloma, recovery from immunoparesis after autologous haematopoietic stem cell transplantation has historically been associated with improved outcomes. However, these findings have not been validated among patients uniformly treated with modern maintenance. This subanalysis of the ATLAS trial, which randomized patients to receive maintenance with carfilzomib, lenalidomide and dexamethasone, or lenalidomide alone, does not confirm the prognostic significance of polyclonal immunoglobulin recovery. The design of the ATLAS trial, including the de‐escalation of therapy in a subset of patients initially treated with carfilzomib, lenalidomide and dexamethasone, allowed for the analysis of the effects of different treatment regimens on humoral immunity.</description><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>carfilzomib</subject><subject>Dexamethasone</subject><subject>Dexamethasone - therapeutic use</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hematopoietic stem cells</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>immunoparesis</subject><subject>Immunotherapy</subject><subject>lenalidomide</subject><subject>Lenalidomide - therapeutic use</subject><subject>maintenance</subject><subject>Minimal residual disease</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - drug therapy</subject><subject>myeloma</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Targeted cancer therapy</subject><subject>Transplantation, Autologous</subject><subject>Transplants & implants</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kk1v1DAQhgMC0aVw4A-gkeAAEtva63w43JYKKGglkFrO0SSZ7Hrl2MF2uqS_HoctHCrhy9jW4_edGU-SvODsjMd1Xu93Z7xkZfEwWXCRZ8sVT_mjZMEYK5acpfIkeer9njEuWMafJCeiyEvOWLZ48Pq71VOjrUENqu9HY7fa1qNWBhw19obcBHE_YFBkgoeDCjswdNATtAq3xnpqoZ9I2x7nF6RulNlCj8oEMmgagrAjh8ME2AVygGOw2m7t6GGH1GOwg1UUVAM-UA8NaQ3BofGDRhOirTVHU1KzEDToOqVvba_qd6CjhVZtPLQEaFpo6Rf2FHborSGw7h4R66T3cDXWGG8nrzzYbs4PouHM3MZihviYQMD6erO-iqko1M-Sxx1qT8_v4mny49PH64vL5ebb5y8X682yEVIWSykZW4k0hpzXZZG3WMq6yDLBmRCd5AWvSZQFF63o8gzTfFWzhvFclphT3pA4Td4cdQdnf47kQ9UrP3cEDcWGVSuZx59LJZMRfXUP3dvRxapmqkxXpZCliNTbI9U4672jrhqc6tFNFWfVPDpVHJ3qz-hE9uWd4lj31P4j_85KBM6PwEFpmv6vVH34enmU_A0uiNTD</recordid><startdate>202312</startdate><enddate>202312</enddate><creator>Kubicki, Tadeusz</creator><creator>Dytfeld, Dominik</creator><creator>Wróbel, Tomasz</creator><creator>Jamroziak, Krzysztof</creator><creator>Robak, Paweł</creator><creator>Czyż, Jarosław</creator><creator>Tyczyńska, Agata</creator><creator>Druzd‐Sitek, Agnieszka</creator><creator>Giannopoulos, Krzysztof</creator><creator>Szczepaniak, Tomasz</creator><creator>Łojko‐Dankowska, Anna</creator><creator>Matuszak, Magdalena</creator><creator>Gil, Lidia</creator><creator>Puła, Bartosz</creator><creator>Rybka, Justyna</creator><creator>Majcherek, Maciej</creator><creator>Usnarska‐Zubkiewicz, Lidia</creator><creator>Szukalski, Łukasz</creator><creator>Zaucha, Jan Maciej</creator><creator>Mikulski, Damian</creator><creator>Czabak, Olga</creator><creator>Lahoud, Oscar B.</creator><creator>Stefka, Andrew</creator><creator>Derman, Benjamin A.</creator><creator>Jakubowiak, Andrzej J.</creator><general>Blackwell Publishing Ltd</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0116-5002</orcidid><orcidid>https://orcid.org/0000-0002-4178-7837</orcidid><orcidid>https://orcid.org/0000-0002-6612-3535</orcidid><orcidid>https://orcid.org/0000-0003-0700-3637</orcidid><orcidid>https://orcid.org/0000-0002-2806-2583</orcidid><orcidid>https://orcid.org/0000-0003-0209-3282</orcidid><orcidid>https://orcid.org/0000-0002-2067-2715</orcidid><orcidid>https://orcid.org/0000-0002-9885-5140</orcidid><orcidid>https://orcid.org/0000-0002-8501-8386</orcidid><orcidid>https://orcid.org/0000-0002-5893-1989</orcidid><orcidid>https://orcid.org/0000-0002-7651-3430</orcidid><orcidid>https://orcid.org/0000-0002-0986-8936</orcidid><orcidid>https://orcid.org/0000-0002-9083-9058</orcidid><orcidid>https://orcid.org/0000-0002-6078-5415</orcidid><orcidid>https://orcid.org/0000-0001-7588-1453</orcidid><orcidid>https://orcid.org/0000-0002-2597-6822</orcidid><orcidid>https://orcid.org/0000-0003-0135-4030</orcidid><orcidid>https://orcid.org/0000-0002-3291-286X</orcidid><orcidid>https://orcid.org/0000-0001-6064-296X</orcidid><orcidid>https://orcid.org/0000-0003-0855-6591</orcidid><orcidid>https://orcid.org/0000-0001-7207-8534</orcidid><orcidid>https://orcid.org/0000-0002-4070-1819</orcidid></search><sort><creationdate>202312</creationdate><title>Polyclonal immunoglobulin recovery in patients with newly diagnosed myeloma receiving maintenance therapy after autologous haematopoietic stem cell transplantation with either carfilzomib, lenalidomide and dexamethasone or lenalidomide alone: Subanalysis of the randomized phase 3 ATLAS trial</title><author>Kubicki, Tadeusz ; Dytfeld, Dominik ; Wróbel, Tomasz ; Jamroziak, Krzysztof ; Robak, Paweł ; Czyż, Jarosław ; Tyczyńska, Agata ; Druzd‐Sitek, Agnieszka ; Giannopoulos, Krzysztof ; Szczepaniak, Tomasz ; Łojko‐Dankowska, Anna ; Matuszak, Magdalena ; Gil, Lidia ; Puła, Bartosz ; Rybka, Justyna ; Majcherek, Maciej ; Usnarska‐Zubkiewicz, Lidia ; Szukalski, Łukasz ; Zaucha, Jan Maciej ; Mikulski, Damian ; Czabak, Olga ; Lahoud, Oscar B. ; Stefka, Andrew ; Derman, Benjamin A. ; Jakubowiak, Andrzej J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3887-880023488061b976da98b75531033f8171be39713d3f65a462b0c01689a6e6ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>carfilzomib</topic><topic>Dexamethasone</topic><topic>Dexamethasone - therapeutic use</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Hematopoietic stem cells</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>immunoparesis</topic><topic>Immunotherapy</topic><topic>lenalidomide</topic><topic>Lenalidomide - therapeutic use</topic><topic>maintenance</topic><topic>Minimal residual disease</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - drug therapy</topic><topic>myeloma</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Targeted cancer therapy</topic><topic>Transplantation, Autologous</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kubicki, Tadeusz</creatorcontrib><creatorcontrib>Dytfeld, Dominik</creatorcontrib><creatorcontrib>Wróbel, Tomasz</creatorcontrib><creatorcontrib>Jamroziak, Krzysztof</creatorcontrib><creatorcontrib>Robak, Paweł</creatorcontrib><creatorcontrib>Czyż, Jarosław</creatorcontrib><creatorcontrib>Tyczyńska, Agata</creatorcontrib><creatorcontrib>Druzd‐Sitek, Agnieszka</creatorcontrib><creatorcontrib>Giannopoulos, Krzysztof</creatorcontrib><creatorcontrib>Szczepaniak, Tomasz</creatorcontrib><creatorcontrib>Łojko‐Dankowska, Anna</creatorcontrib><creatorcontrib>Matuszak, Magdalena</creatorcontrib><creatorcontrib>Gil, Lidia</creatorcontrib><creatorcontrib>Puła, Bartosz</creatorcontrib><creatorcontrib>Rybka, Justyna</creatorcontrib><creatorcontrib>Majcherek, Maciej</creatorcontrib><creatorcontrib>Usnarska‐Zubkiewicz, Lidia</creatorcontrib><creatorcontrib>Szukalski, Łukasz</creatorcontrib><creatorcontrib>Zaucha, Jan Maciej</creatorcontrib><creatorcontrib>Mikulski, Damian</creatorcontrib><creatorcontrib>Czabak, Olga</creatorcontrib><creatorcontrib>Lahoud, Oscar B.</creatorcontrib><creatorcontrib>Stefka, Andrew</creatorcontrib><creatorcontrib>Derman, Benjamin A.</creatorcontrib><creatorcontrib>Jakubowiak, Andrzej J.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kubicki, Tadeusz</au><au>Dytfeld, Dominik</au><au>Wróbel, Tomasz</au><au>Jamroziak, Krzysztof</au><au>Robak, Paweł</au><au>Czyż, Jarosław</au><au>Tyczyńska, Agata</au><au>Druzd‐Sitek, Agnieszka</au><au>Giannopoulos, Krzysztof</au><au>Szczepaniak, Tomasz</au><au>Łojko‐Dankowska, Anna</au><au>Matuszak, Magdalena</au><au>Gil, Lidia</au><au>Puła, Bartosz</au><au>Rybka, Justyna</au><au>Majcherek, Maciej</au><au>Usnarska‐Zubkiewicz, Lidia</au><au>Szukalski, Łukasz</au><au>Zaucha, Jan Maciej</au><au>Mikulski, Damian</au><au>Czabak, Olga</au><au>Lahoud, Oscar B.</au><au>Stefka, Andrew</au><au>Derman, Benjamin A.</au><au>Jakubowiak, Andrzej J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polyclonal immunoglobulin recovery in patients with newly diagnosed myeloma receiving maintenance therapy after autologous haematopoietic stem cell transplantation with either carfilzomib, lenalidomide and dexamethasone or lenalidomide alone: Subanalysis of the randomized phase 3 ATLAS trial</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2023-12</date><risdate>2023</risdate><volume>203</volume><issue>5</issue><spage>792</spage><epage>802</epage><pages>792-802</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><abstract>Summary
Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B‐cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance. In the KRd arm, standard‐risk patients with minimal residual disease negativity after six cycles de‐escalated to R alone after cycle 8. One year from the initiation of maintenance at least partial recovery of polyclonal immunoglobulin was observed in more patients on the R arm (58/66, p < 0.001) and in those who de‐escalated from KRd to R (27/38, p < 0.001) compared to the KRd arm (9/36). In patients who switched from KRd to R, the concentrations of uninvolved immunoglobulin and the number of B‐cell unique sequences increased over time, approaching values observed in the R arm. There were no differences in progression‐free survival between the patients with at least partial immunoglobulin recovery and the remaining population. Our analysis indicates that patients receiving continuous therapy after ASCT experience prolonged immunoparesis, limiting prognostic significance of polyclonal immunoglobulin recovery in this setting.
In multiple myeloma, recovery from immunoparesis after autologous haematopoietic stem cell transplantation has historically been associated with improved outcomes. However, these findings have not been validated among patients uniformly treated with modern maintenance. This subanalysis of the ATLAS trial, which randomized patients to receive maintenance with carfilzomib, lenalidomide and dexamethasone, or lenalidomide alone, does not confirm the prognostic significance of polyclonal immunoglobulin recovery. The design of the ATLAS trial, including the de‐escalation of therapy in a subset of patients initially treated with carfilzomib, lenalidomide and dexamethasone, allowed for the analysis of the effects of different treatment regimens on humoral immunity.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>37691005</pmid><doi>10.1111/bjh.19097</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-0116-5002</orcidid><orcidid>https://orcid.org/0000-0002-4178-7837</orcidid><orcidid>https://orcid.org/0000-0002-6612-3535</orcidid><orcidid>https://orcid.org/0000-0003-0700-3637</orcidid><orcidid>https://orcid.org/0000-0002-2806-2583</orcidid><orcidid>https://orcid.org/0000-0003-0209-3282</orcidid><orcidid>https://orcid.org/0000-0002-2067-2715</orcidid><orcidid>https://orcid.org/0000-0002-9885-5140</orcidid><orcidid>https://orcid.org/0000-0002-8501-8386</orcidid><orcidid>https://orcid.org/0000-0002-5893-1989</orcidid><orcidid>https://orcid.org/0000-0002-7651-3430</orcidid><orcidid>https://orcid.org/0000-0002-0986-8936</orcidid><orcidid>https://orcid.org/0000-0002-9083-9058</orcidid><orcidid>https://orcid.org/0000-0002-6078-5415</orcidid><orcidid>https://orcid.org/0000-0001-7588-1453</orcidid><orcidid>https://orcid.org/0000-0002-2597-6822</orcidid><orcidid>https://orcid.org/0000-0003-0135-4030</orcidid><orcidid>https://orcid.org/0000-0002-3291-286X</orcidid><orcidid>https://orcid.org/0000-0001-6064-296X</orcidid><orcidid>https://orcid.org/0000-0003-0855-6591</orcidid><orcidid>https://orcid.org/0000-0001-7207-8534</orcidid><orcidid>https://orcid.org/0000-0002-4070-1819</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-1048 |
| ispartof | British journal of haematology, 2023-12, Vol.203 (5), p.792-802 |
| issn | 0007-1048 1365-2141 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2863764808 |
| source | Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Antineoplastic Combined Chemotherapy Protocols - therapeutic use carfilzomib Dexamethasone Dexamethasone - therapeutic use Hematology Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic stem cells Humans Immunoglobulins immunoparesis Immunotherapy lenalidomide Lenalidomide - therapeutic use maintenance Minimal residual disease Multiple myeloma Multiple Myeloma - drug therapy myeloma Stem cell transplantation Stem cells Targeted cancer therapy Transplantation, Autologous Transplants & implants |
| title | Polyclonal immunoglobulin recovery in patients with newly diagnosed myeloma receiving maintenance therapy after autologous haematopoietic stem cell transplantation with either carfilzomib, lenalidomide and dexamethasone or lenalidomide alone: Subanalysis of the randomized phase 3 ATLAS trial |
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