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. 2021 Dec 22;11(1):27.
doi: 10.3390/jcm11010027.

Health-Related Quality of Life Outcomes in Patients with Myelodysplastic Syndromes with Ring Sideroblasts Treated with Luspatercept in the MEDALIST Phase 3 Trial

Esther Natalie Oliva  1 , Uwe Platzbecker  2 , Guillermo Garcia-Manero  3 , Ghulam J Mufti  4 , Valeria Santini  5 , Mikkael A Sekeres  6 , Rami S Komrokji  7 , Jeevan K Shetty  8 , Derek Tang  8 , Shien Guo  9 , Weiqin Liao  9 , George Zhang  8 , Xianwei Ha  8 , Rodrigo Ito  8 , Jennifer Lord-Bessen  8 , Jay T Backstrom  10 , Pierre Fenaux  11   12
Affiliations

Health-Related Quality of Life Outcomes in Patients with Myelodysplastic Syndromes with Ring Sideroblasts Treated with Luspatercept in the MEDALIST Phase 3 Trial

Esther Natalie Oliva et al. J Clin Med. .

Abstract

Patients with myelodysplastic syndromes (MDS) often experience chronic anemia and long-term red blood cell transfusion dependence associated with significant burden on clinical and health-related quality of life (HRQoL) outcomes. In the MEDALIST trial (NCT02631070), luspatercept significantly reduced transfusion burden in patients with lower-risk MDS who had ring sideroblasts and were refractory to, intolerant to, or ineligible for prior treatment with erythropoiesis-stimulating agents. We evaluated the effect of luspatercept on HRQoL in patients enrolled in MEDALIST using the EORTC QLQ-C30 and the QOL-E questionnaire. Change in HRQoL was assessed every 6 weeks in patients receiving luspatercept with best supportive care (+ BSC) and placebo + BSC from baseline through week 25. No clinically meaningful within-group changes and between-group differences across all domains of the EORTC QLQ-C30 and QOL-E were observed. On one item of the QOL-E MDS-specific disturbances domain, patients treated with luspatercept reported marked improvements in their daily life owing to the reduced transfusion burden, relative to placebo. Taken together with previous reports of luspatercept + BSC reducing transfusion burden in patients from baseline through week 25 in MEDALIST, these results suggest luspatercept may offer a treatment option for patients that reduces transfusion burden while providing stability in HRQoL.

Keywords: luspatercept; myelodysplastic syndromes; quality of life; transfusion dependence.

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Conflict of interest statement

Ester N. Oliva: consultancy, honoraria for/from Amgen, BMS, and Novartis; honoraria, patents, royalties, speakers’ bureau from/for BMS. Uwe Platzbecker: consultancy, honoraria for/from BMS, Janssen, and Novartis; research funding from Amgen, Janssen, Merck, and Novartis. Guillermo Garcia-Manero: consultancy for Astex Pharmaceuticals, BMS, Genentech, Helsinn Therapeutics; research funding from AbbVie, Amphivena Therapeutics, Aprea, Astex Pharmaceuticals, BMS, Curis, Forty Seven, Genentech, Helsinn Therapeutics, H3 Biomedicine, Janssen, Merck, Novartis, Onconova. Ghulam J. Mufti: research funding from Aplastic Anaemia Trust, Bloodwise UK/Leukaemia and Lymphoma Research Programme, BMS, Cancer Research UK, Life Arc, and Novartis. Valeria Santini: research funding from Janssen; honoraria from BMS, Johnson & Johnson, and Novartis; consultancy for Acceleron Pharma, BMS, Menarini, and Novartis; membership on an entity’s board of directors or advisory committees for Pfizer and Takeda. Mikkael A. Sekeres: membership on an entity’s board of directors or advisory committees for BMS, Millennium/Takeda, and Novartis. Rami S. Komrokji: honoraria from AbbVie, Acceleron Pharma, Agios, BMS, Geron, Jazz Pharmaceuticals, and Novartis; speakers’ bureau for BMS and Jazz Pharmaceuticals. Jeevan K. Shetty, George Zhang, and Xianwei Ha: employment at BMS. Derek Tang and Jennifer Lord-Bessen: employment, equity ownership at BMS. Rodrigo Ito: former employment at BMS during time of study; current employment at Eli Lilly and Company; equity ownership at BMS, Eli Lilly and Company. Shien Guo: consultancy for BMS, Gilead, Janssen. Weigin Liao: consultancy for BMS. Jay T. Backstrom: employment, equity ownership at Acceleron Pharma; equity ownership at BMS. Pierre Fenaux: honoraria from BMS.

Figures

Figure 1
Figure 1
(A) Endpoints and (B) assessment schedule for patient-reported HRQoL outcomes in the MEDALIST trial. a Baseline visit. b HRQoL assessed with EORTC QLQ-C30 and QOL-E instruments on days indicated with checkmark (✓). BSC, best supportive care; C, cycle; D, day; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer’s Core Quality of Life Questionnaire; HRQoL, health-related quality of life; MDS, myelodysplastic syndromes; QoL, quality of life; QOL-E, Quality of Life Assessment in MDS questionnaire.
Figure 2
Figure 2
Observed mean change from baseline in patient-reported (A) global health status/QoL, (B) physical functioning, (C) emotional functioning, (D) fatigue, and (E) dyspnea scores through week 25 on the EORTC QLQ-C30. Dashed lines indicate threshold for a clinically meaningful difference. In (A–C), higher scores represent better QoL; in (D,E), higher scores represent worse QoL. BSC, best supportive care; C, cycle; D, day; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer’s Core Quality of Life Questionnaire; QoL, quality of life; SE, standard error.
Figure 3
Figure 3
Observed mean change from baseline in patient-reported (A) General (summary of all domain scores except for MDS-specific disturbances) and (B) MDS-specific disturbances scores through week 25 on the QOL-E. Dashed lines indicate threshold for a clinically meaningful difference. BSC, best supportive care; C, cycle; D, day; MDS, myelodysplastic syndromes; QOL-E, Quality of Life Assessment in MDS questionnaire; SE, standard error.
Figure 4
Figure 4
Patient-reported impact of transfusion burden by QOL-E from treatment initiation through week 25. Question from the QOL-E instrument: What effect of the disease disturbs your daily life? Being dependent on transfusions; response options: “No, not at all”, “A little bit”, or “Yes, extremely”. Responses at each timepoint were compared with responses at baseline to assess if patients had improved, remained stable, or experienced worsening. BSC, best supportive care; C3D1, cycle 3 day 1 (and similarly for C5D1 and C7D1); MDS, myelodysplastic syndromes; QOL-E, Quality of Life Assessment in MDS questionnaire.
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References

    1. Zeidan A.M., Linhares Y., Gore S.D. Current therapy of myelodysplastic syndromes. Blood Rev. 2013;27:243–259. doi: 10.1016/j.blre.2013.07.003. - DOI - PMC - PubMed
    1. Adès L., Itzykson R., Fenaux P. Myelodysplastic syndromes. Lancet. 2014;383:2239–2252. doi: 10.1016/S0140-6736(13)61901-7. - DOI - PubMed
    1. Malcovati L. Red blood cell transfusion therapy and iron chelation in patients with myelodysplastic syndromes. Clin. Lymphoma Myeloma. 2009;9((Suppl. 3)):S305–S311. doi: 10.3816/CLM.2009.s.029. - DOI - PubMed
    1. Steensma D.P., Heptinstall K.V., Johnson V.M., Novotny P.J., Sloan J.A., Camoriano J.K., Niblack J., Bennett J.M., Mesa R.A. Common troublesome symptoms and their impact on quality of life in patients with myelodysplastic syndromes (MDS): Results of a large internet-based survey. Leuk. Res. 2008;32:691–698. doi: 10.1016/j.leukres.2007.10.015. - DOI - PubMed
    1. Sobrero A., Puglisi F., Guglielmi A., Belvedere O., Aprile G., Ramello M., Grossi F. Fatigue: A main component of anemia symptomatology. Semin. Oncol. 2001;28((Suppl. 8)):15–18. doi: 10.1016/S0093-7754(01)90207-6. - DOI - PubMed