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

Dan Vogl¹  Moshe Levy²  Karlin Lionel³  Gary Schiller⁴  David Siegel⁵  Noa Biran⁵  Paul Richardson⁶  Mohamad Mohty⁷  Frenzel Laurent⁸  Ajaj Chari⁹  Nathalie Meuleman^1,10  Sharon Shacham^1,11  Lingling Li^1,11  Jatin Shah^1,11  Michael Kauffman^1,11  Sylvain Choquet^1,12  Sascha Tuchman^1,13  David Dingli^1,14  David Kaminetzky^1,15  Maria Gavriatopoulou^1,16  Gabriel Tremblay^1,17  Patrick Daniele^1,17  Janis Breeze^1,17  Meletios-Athanasios Dimopoulos^1,18  James E. Hoffman^1,19  Joshua Richter^2,20  Jagannath Sundar^2,20  Philip Vlummens^2,21  Klaus Podar^2,22  Martin Schreder^2,23  Thierry Facon^2,24  Katja Weisel^2,25  Luciano Costa^2,26  Monika Engelhardt^2,27  Marc Raab^2,28  Michel Delforge^2,29  Philippe Moreau^3,30  Chantal Doyen^3,31  Robert Frank Cornell^3,32  Ravi Vij^3,33  Ajay Nooka^3,34  Terri Parker^3,35 

[1] Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA;Baylor University Medical Center, Dallas, USA;Centre Hospitalier Lyon Sud, Saint-Genis-Laval, France;David Geffen School of Medicine at University of California, Los Angeles, USA;Hackensack Meridian Health Hackensack University Medical Center, Hackensack, USA;Harvard Cancer Center, Boston, USA;Hopital Saint-Antoine, Paris, France;Hôpital Necker, Paris, France;Icahn School of Medicine at Mount Sinai, New York, USA;Institut Jules Bordet, Brussels, Belgium;Karyopharm Therapeutics Inc., Newton, USA;La Pitié Salpêtrière Hospital, Paris, France;Lineberger Comprehensive Cancer Center at University of North Carolina-Chapel Hill, Chapel Hill, USA;Mayo Clinic, Rochester, USA;New York University Langone Medical Center, New York, USA;Oncology Department, Alexandra Hospital, Athens, Greece;Purple Squirrel Economics, 1600 Notre Dame W, Suite 201, H3J 1M1, Montreal, QC, Canada;School of Medicine, National and Kapodistrian University of Athens, Athens, Greece;Sylvester Cancer Center, University of Miami, Miami, USA;Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA;University Hospital Ghent, Ghent, Belgium;University Hospital Krems, Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria;University Hospital Würzburg, Würzburg, Germany;University Hospital, Lille, France;University Medical Center Hamburg-Eppendorf, Hamburg, Germany;University of Alabama at Birmingham, Birmingham, USA;University of Freiburg, Freiburg im Breisgau, Germany;University of Heidelberg, Heidelberg, Germany;University of Leuven, Leuven, Belgium;University of Nantes, Nantes, France;Université catholique de Louvain, Ottignies-Louvain-la-Neuve, Belgium;Vanderbilt University Medical Center, Nashville, USA;Washington University School of Medicine, St. Louis, USA;Winship Cancer Institute, Emory University, Atlanta, USA;Yale School of Medicine, New Haven, USA;

关键词: Patient reported outcomes;    Health-related quality of life;    FACT-MM;    Multiple myeloma;    Selinexor;   

DOI  :  10.1186/s12885-021-08453-9

来源: Springer

【 摘 要 】

BackgroundSelinexor 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.MethodsFACT-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.ResultsEighty 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.ConclusionThe 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 registrationThis trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015.

【 授权许可】

CC BY