Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study
Authors: Tremblay Gabriel , Daniele Patrick , Breeze Janis , Li Lingling , Shah Jatin , Shacham Sharon , Kauffman Michael , Engelhardt Monika , Chari Ajaj , Nooka Ajay , Vogl Dan , Gavriatopoulou Maria , Dimopoulos Meletios-Athanasios , Richardson Paul , Biran Noa , Siegel David , Vlummens Philip , Doyen Chantal , Facon Thierry , Mohty Mohamad , Meuleman Nathalie , Levy Moshe , Costa Luciano , Hoffman James E. , Delforge Michel , Kaminetzky David , Weisel Katja , Raab Marc , Dingli David , Tuchman Sascha , Laurent Frenzel , Vij Ravi , Schiller Gary , Moreau Philippe , Richter Joshua , Schreder Martin , Podar Klaus , Parker Terri , Cornell Robert Frank , Lionel Karlin , Choquet Sylvain , Sundar Jagannath 
Published: September 2021

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.