Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study
Abstract Background Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overal...
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2021-09-01
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Series: | BMC Cancer |
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Online Access: | https://doi.org/10.1186/s12885-021-08453-9 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gabriel Tremblay Patrick Daniele Janis Breeze Lingling Li Jatin Shah Sharon Shacham Michael Kauffman Monika Engelhardt Ajaj Chari Ajay Nooka Dan Vogl Maria Gavriatopoulou Meletios-Athanasios Dimopoulos Paul Richardson Noa Biran David Siegel Philip Vlummens Chantal Doyen Thierry Facon Mohamad Mohty Nathalie Meuleman Moshe Levy Luciano Costa James E. Hoffman Michel Delforge David Kaminetzky Katja Weisel Marc Raab David Dingli Sascha Tuchman Frenzel Laurent Ravi Vij Gary Schiller Philippe Moreau Joshua Richter Martin Schreder Klaus Podar Terri Parker Robert Frank Cornell Karlin Lionel Sylvain Choquet Jagannath Sundar |
spellingShingle |
Gabriel Tremblay Patrick Daniele Janis Breeze Lingling Li Jatin Shah Sharon Shacham Michael Kauffman Monika Engelhardt Ajaj Chari Ajay Nooka Dan Vogl Maria Gavriatopoulou Meletios-Athanasios Dimopoulos Paul Richardson Noa Biran David Siegel Philip Vlummens Chantal Doyen Thierry Facon Mohamad Mohty Nathalie Meuleman Moshe Levy Luciano Costa James E. Hoffman Michel Delforge David Kaminetzky Katja Weisel Marc Raab David Dingli Sascha Tuchman Frenzel Laurent Ravi Vij Gary Schiller Philippe Moreau Joshua Richter Martin Schreder Klaus Podar Terri Parker Robert Frank Cornell Karlin Lionel Sylvain Choquet Jagannath Sundar Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study BMC Cancer Patient reported outcomes Health-related quality of life FACT-MM Multiple myeloma Selinexor |
author_facet |
Gabriel Tremblay Patrick Daniele Janis Breeze Lingling Li Jatin Shah Sharon Shacham Michael Kauffman Monika Engelhardt Ajaj Chari Ajay Nooka Dan Vogl Maria Gavriatopoulou Meletios-Athanasios Dimopoulos Paul Richardson Noa Biran David Siegel Philip Vlummens Chantal Doyen Thierry Facon Mohamad Mohty Nathalie Meuleman Moshe Levy Luciano Costa James E. Hoffman Michel Delforge David Kaminetzky Katja Weisel Marc Raab David Dingli Sascha Tuchman Frenzel Laurent Ravi Vij Gary Schiller Philippe Moreau Joshua Richter Martin Schreder Klaus Podar Terri Parker Robert Frank Cornell Karlin Lionel Sylvain Choquet Jagannath Sundar |
author_sort |
Gabriel Tremblay |
title |
Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study |
title_short |
Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study |
title_full |
Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study |
title_fullStr |
Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study |
title_full_unstemmed |
Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study |
title_sort |
quality of life analyses in patients with multiple myeloma: results from the selinexor (kpt-330) treatment of refractory myeloma (storm) phase 2b study |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2021-09-01 |
description |
Abstract Background Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy – Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM. Methods FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders. Results Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores. Conclusion The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach. Trial registration This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015. |
topic |
Patient reported outcomes Health-related quality of life FACT-MM Multiple myeloma Selinexor |
url |
https://doi.org/10.1186/s12885-021-08453-9 |
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doaj-ad0d07b841e64c82afc2fcdee19751cf2021-09-12T11:33:07ZengBMCBMC Cancer1471-24072021-09-0121111010.1186/s12885-021-08453-9Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b studyGabriel Tremblay0Patrick Daniele1Janis Breeze2Lingling Li3Jatin Shah4Sharon Shacham5Michael Kauffman6Monika Engelhardt7Ajaj Chari8Ajay Nooka9Dan Vogl10Maria Gavriatopoulou11Meletios-Athanasios Dimopoulos12Paul Richardson13Noa Biran14David Siegel15Philip Vlummens16Chantal Doyen17Thierry Facon18Mohamad Mohty19Nathalie Meuleman20Moshe Levy21Luciano Costa22James E. Hoffman23Michel Delforge24David Kaminetzky25Katja Weisel26Marc Raab27David Dingli28Sascha Tuchman29Frenzel Laurent30Ravi Vij31Gary Schiller32Philippe Moreau33Joshua Richter34Martin Schreder35Klaus Podar36Terri Parker37Robert Frank Cornell38Karlin Lionel39Sylvain Choquet40Jagannath Sundar41Purple Squirrel EconomicsPurple Squirrel EconomicsPurple Squirrel EconomicsKaryopharm Therapeutics Inc.Karyopharm Therapeutics Inc.Karyopharm Therapeutics Inc.Karyopharm Therapeutics Inc.University of FreiburgIcahn School of Medicine at Mount SinaiWinship Cancer Institute, Emory UniversityAbramson Cancer Center, Perelman School of Medicine, University of PennsylvaniaOncology Department, Alexandra HospitalSchool of Medicine, National and Kapodistrian University of AthensHarvard Cancer CenterHackensack Meridian Health Hackensack University Medical CenterHackensack Meridian Health Hackensack University Medical CenterUniversity Hospital GhentUniversité catholique de LouvainUniversity HospitalHopital Saint-AntoineInstitut Jules BordetBaylor University Medical CenterUniversity of Alabama at BirminghamSylvester Cancer Center, University of MiamiUniversity of LeuvenNew York University Langone Medical CenterUniversity Medical Center Hamburg-EppendorfUniversity of HeidelbergMayo ClinicLineberger Comprehensive Cancer Center at University of North Carolina-Chapel HillHôpital NeckerWashington University School of MedicineDavid Geffen School of Medicine at University of CaliforniaUniversity of NantesTisch Cancer Institute, Icahn School of Medicine at Mount SinaiUniversity Hospital WürzburgUniversity Hospital Krems, Karl Landsteiner University of Health SciencesYale School of MedicineVanderbilt University Medical CenterCentre Hospitalier Lyon SudLa Pitié Salpêtrière HospitalTisch Cancer Institute, Icahn School of Medicine at Mount SinaiAbstract Background Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy – Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM. Methods FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders. Results Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores. Conclusion The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach. Trial registration This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015.https://doi.org/10.1186/s12885-021-08453-9Patient reported outcomesHealth-related quality of lifeFACT-MMMultiple myelomaSelinexor |