In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma management
Abstract Long-term proteasome inhibitor (PI) treatment can improve multiple myeloma (MM) outcomes, but this can be difficult to achieve in clinical practice due to toxicity, comorbidities, and the burden of repeated parenteral administration. US MM-6 (NCT03173092) enrolled transplant-ineligible pati...
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Nature Publishing Group
2023-09-01
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Series: | Blood Cancer Journal |
Online Access: | https://doi.org/10.1038/s41408-023-00912-9 |
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author | Robert M. Rifkin Saulius K. Girnius Stephen J. Noga Ruemu E. Birhiray Suman Kambhampati Sudhir Manda Roger M. Lyons Habte A. Yimer Dasha Cherepanov Eric Lloyd Presley Whidden Joshua Richter |
author_facet | Robert M. Rifkin Saulius K. Girnius Stephen J. Noga Ruemu E. Birhiray Suman Kambhampati Sudhir Manda Roger M. Lyons Habte A. Yimer Dasha Cherepanov Eric Lloyd Presley Whidden Joshua Richter |
author_sort | Robert M. Rifkin |
collection | DOAJ |
description | Abstract Long-term proteasome inhibitor (PI) treatment can improve multiple myeloma (MM) outcomes, but this can be difficult to achieve in clinical practice due to toxicity, comorbidities, and the burden of repeated parenteral administration. US MM-6 (NCT03173092) enrolled transplant-ineligible patients with newly diagnosed MM to receive all-oral ixazomib-lenalidomide-dexamethasone (IRd; ≤39 cycles or until progression or toxicity) following three cycles of bortezomib-based induction. Primary endpoint: 2-year progression-free survival (PFS). Key secondary/exploratory endpoints included overall response rate (ORR), overall survival (OS), safety, quality of life (QoL), treatment satisfaction, and actigraphy. At datacut, in the fully accrued cohort of 140 patients, median age was 73 years with 42% aged ≥75 and 61% deemed frail; 10% of patients were ongoing on treatment. After a median follow-up of 27 months, the 2-year PFS rate was 71% (95% confidence interval: 61–78). ORR increased from 62% at the end of induction to 80% following in-class transition (iCT) to IRd for a median of 11 months. The 2-year OS rate was 86%. The overall safety profile/actigraphy levels were consistent with previous reports; QoL/treatment satisfaction scores were stable with ongoing therapy. iCT to IRd may allow prolonged PI-based therapy with promising efficacy and a tolerable safety profile, while maintaining QoL. |
first_indexed | 2024-03-09T15:28:08Z |
format | Article |
id | doaj.art-4610ad81300445efb624a0ed2b1b1a3e |
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issn | 2044-5385 |
language | English |
last_indexed | 2024-03-09T15:28:08Z |
publishDate | 2023-09-01 |
publisher | Nature Publishing Group |
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series | Blood Cancer Journal |
spelling | doaj.art-4610ad81300445efb624a0ed2b1b1a3e2023-11-26T12:23:38ZengNature Publishing GroupBlood Cancer Journal2044-53852023-09-0113111210.1038/s41408-023-00912-9In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma managementRobert M. Rifkin0Saulius K. Girnius1Stephen J. Noga2Ruemu E. Birhiray3Suman Kambhampati4Sudhir Manda5Roger M. Lyons6Habte A. Yimer7Dasha Cherepanov8Eric Lloyd9Presley Whidden10Joshua Richter11Rocky Mountain Cancer Centers/US Oncology ResearchTrihealth Cancer InstituteTakeda Pharmaceuticals U.S.A., Inc.Hematology Oncology of Indiana/American Oncology NetworkKansas City Veterans Affairs Medical CenterArizona Oncology/US Oncology ResearchTexas Oncology/US Oncology ResearchTexas Oncology/US Oncology ResearchTakeda Development Center Americas, Inc. (TDCA)Takeda Pharmaceuticals U.S.A., Inc.Takeda Pharmaceuticals U.S.A., Inc.Tisch Cancer Institute, Icahn School of Medicine at Mount SinaiAbstract Long-term proteasome inhibitor (PI) treatment can improve multiple myeloma (MM) outcomes, but this can be difficult to achieve in clinical practice due to toxicity, comorbidities, and the burden of repeated parenteral administration. US MM-6 (NCT03173092) enrolled transplant-ineligible patients with newly diagnosed MM to receive all-oral ixazomib-lenalidomide-dexamethasone (IRd; ≤39 cycles or until progression or toxicity) following three cycles of bortezomib-based induction. Primary endpoint: 2-year progression-free survival (PFS). Key secondary/exploratory endpoints included overall response rate (ORR), overall survival (OS), safety, quality of life (QoL), treatment satisfaction, and actigraphy. At datacut, in the fully accrued cohort of 140 patients, median age was 73 years with 42% aged ≥75 and 61% deemed frail; 10% of patients were ongoing on treatment. After a median follow-up of 27 months, the 2-year PFS rate was 71% (95% confidence interval: 61–78). ORR increased from 62% at the end of induction to 80% following in-class transition (iCT) to IRd for a median of 11 months. The 2-year OS rate was 86%. The overall safety profile/actigraphy levels were consistent with previous reports; QoL/treatment satisfaction scores were stable with ongoing therapy. iCT to IRd may allow prolonged PI-based therapy with promising efficacy and a tolerable safety profile, while maintaining QoL.https://doi.org/10.1038/s41408-023-00912-9 |
spellingShingle | Robert M. Rifkin Saulius K. Girnius Stephen J. Noga Ruemu E. Birhiray Suman Kambhampati Sudhir Manda Roger M. Lyons Habte A. Yimer Dasha Cherepanov Eric Lloyd Presley Whidden Joshua Richter In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma management Blood Cancer Journal |
title | In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma management |
title_full | In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma management |
title_fullStr | In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma management |
title_full_unstemmed | In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma management |
title_short | In-class transition (iCT) of proteasome inhibitor-based therapy: a community approach to multiple myeloma management |
title_sort | in class transition ict of proteasome inhibitor based therapy a community approach to multiple myeloma management |
url | https://doi.org/10.1038/s41408-023-00912-9 |
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