Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry
Abstract Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by imm...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-03-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-024-00995-y |
| _version_ | 1797247448167481344 |
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| author | H. V. Giles M. T. Drayson B. Kishore C. Pawlyn M. Kaiser G. Cook R. de Tute R. G. Owen D. Cairns T. Menzies F. E. Davies G. J. Morgan G. Pratt G. H. Jackson |
| author_facet | H. V. Giles M. T. Drayson B. Kishore C. Pawlyn M. Kaiser G. Cook R. de Tute R. G. Owen D. Cairns T. Menzies F. E. Davies G. J. Morgan G. Pratt G. H. Jackson |
| author_sort | H. V. Giles |
| collection | DOAJ |
| description | Abstract Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression. |
| first_indexed | 2024-04-24T19:58:51Z |
| format | Article |
| id | doaj.art-0e9a723e00fb40978aa075c750847b8d |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-04-24T19:58:51Z |
| publishDate | 2024-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-0e9a723e00fb40978aa075c750847b8d2024-03-24T12:10:58ZengNature Publishing GroupBlood Cancer Journal2044-53852024-03-0114111010.1038/s41408-024-00995-yProgression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometryH. V. Giles0M. T. Drayson1B. Kishore2C. Pawlyn3M. Kaiser4G. Cook5R. de Tute6R. G. Owen7D. Cairns8T. Menzies9F. E. Davies10G. J. Morgan11G. Pratt12G. H. Jackson13University Hospitals Birmingham NHS Foundation TrustUniversity of BirminghamUniversity Hospitals Birmingham NHS Foundation TrustThe Institute of Cancer Research, London and The Royal Marsden HospitalThe Institute of Cancer Research, London and The Royal Marsden HospitalLeeds Cancer Research UK Institute of Clinical Trials Research, University of LeedsHaematological Malignancy Diagnostic Service, Leeds Teaching Hospitals TrustHaematological Malignancy Diagnostic Service, Leeds Teaching Hospitals TrustLeeds Cancer Research UK Institute of Clinical Trials Research, University of LeedsLeeds Cancer Research UK Institute of Clinical Trials Research, University of LeedsMyeloma Research Program, Perlmutter Cancer, NYU Langone HealthMyeloma Research Program, Perlmutter Cancer, NYU Langone HealthUniversity Hospitals Birmingham NHS Foundation TrustDepartment of Haematology, University of NewcastleAbstract Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression.https://doi.org/10.1038/s41408-024-00995-y |
| spellingShingle | H. V. Giles M. T. Drayson B. Kishore C. Pawlyn M. Kaiser G. Cook R. de Tute R. G. Owen D. Cairns T. Menzies F. E. Davies G. J. Morgan G. Pratt G. H. Jackson Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry Blood Cancer Journal |
| title | Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry |
| title_full | Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry |
| title_fullStr | Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry |
| title_full_unstemmed | Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry |
| title_short | Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry |
| title_sort | progression free survival of myeloma patients who become ife negative correlates with the detection of residual monoclonal free light chain flc by mass spectrometry |
| url | https://doi.org/10.1038/s41408-024-00995-y |
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