THE BEYOND STUDY: RESULTS OF A PHASE 2, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED MULTICENTER STUDY OF LUSPATERCEPT IN ADULT PATIENTS WITH NON-TRANSFUSION DEPENDENT BETA-THALASSEMIA
Author(s): ,
Ali T. Taher
Affiliations:
Department of Internal Medicine, American University of Beirut Medical Center,Beirut,Lebanon
,
Maria Domenica Cappellini
Affiliations:
Fondazione IRCCS Ca’ Granda Policlinico Hospital, University of Milan,Milan,Italy
,
Antonis Kattamis
Affiliations:
First Department of Pediatrics, National and Kapodistrian University of Athens,Athens, Greece,Greece
,
Ersi Voskaridou
Affiliations:
Thalassemia and Sickle Cell Center of Laiko General Hospital,Athens,Greece
,
Silverio Perrotta
Affiliations:
Università della Campania, Luigi Vanvitelli,Caserta, Italy,Italy
,
Antonio Piga
Affiliations:
Department of Clinical and Biological Sciences, University of Turin,Turin, Italy,Italy
,
Aldo Filosa
Affiliations:
Rare Red Blood Cell Disease Unit,Cardarelli Hospital,Naples,Italy
,
John B. Porter
Affiliations:
University College London, University College London Hospitals,London,United Kingdom
,
Thomas D. Coates
Affiliations:
Cancer and Blood Disease Institute, Children's Hospital Los Angeles,Los Angeles, CA, United States,United States;USC Keck School of Medicine,Los Angeles, CA,United States
,
Gian Luca Forni
Affiliations:
Centro della Microcitemia e Anemie Congenite e del Dismetabolismo del Ferro, Ospedale Galliera,Genoa,Italy
,
Alexis Thompson
Affiliations:
Ann & Robert H. Lurie Children’s Hospital of Chicago, Weinberg School of Medicine, Northwestern University,Chicago, IL, United States,United States
,
Jay T. Backstrom
Affiliations:
Acceleron Pharma,Cambridge, MA,United States
,
Oriana Esposito
Affiliations:
Celgene International Sàrl, a Bristol-Myers Squibb Company,Boudry,Switzerland
,
Wen-Ling Kuo
Affiliations:
Bristol Myers Squibb,Princeton, NJ,United States
,
Dimana Miteva
Affiliations:
Celgene International Sàrl, a Bristol-Myers Squibb Company,Boudry,Switzerland
,
Tatiana Zinger
Affiliations:
Celgene International Sàrl, a Bristol-Myers Squibb Company,Boudry,Switzerland
,
Jeevan K. Shetty
Affiliations:
Celgene International Sàrl, a Bristol-Myers Squibb Company,Boudry,Switzerland
Vip Viprakasit
Affiliations:
Siriraj Hospital, Mahidol University,Bangkok,Thailand
EHA Library. T. Taher A. 06/09/21; 324509; S101
Ali T. Taher
Ali T. Taher
Contributions
Abstract
This abstract is embargoed until Friday, June 11, 09:00 CEST

Presentation during EHA2021: The Presidential Symposium will be held on Friday, June 11, 2021 (16:00 - 17:30 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S101

Type: Presidential Symposium

Session title: Presidential Symposium

Background
β-thalassemia is an inherited hemoglobinopathy characterized by ineffective erythropoiesis and impaired red blood cell (RBC) maturation. Patients (pts) with non-transfusion dependent (NTD) β-thalassemia develop chronic anemia and other serious complications affecting survival and quality of life (QoL). Luspatercept, a first-in-class erythroid maturation agent approved by the EMA for treatment of anemia in adults with transfusion-dependent β-thalassemia, may have potential clinical benefit for NTD pts.

Aims
We report results of BEYOND, a phase 2, double-blind, randomized, multicenter study to determine the efficacy and safety of luspatercept vs placebo (PBO) in adults with NTD β-thalassemia (NCT03342404).

Methods
Eligible pts provided informed consent, were ≥18 years with β-thalassemia or hemoglobin (Hb) E/β-thalassemia and received ≤5 RBC units in the 24 weeks (wks) prior to randomization, with mean baseline Hb ≤10.0 g/dL. Pts were randomized 2:1 to receive luspatercept 1 mg/kg (titration up to 1.25 mg/kg) or PBO subcutaneously every 3 wks for ≥48 wks. Pts in both arms continued to receive best supportive care, including sporadic RBC transfusions and iron chelation therapy.

The primary endpoint was achievement of ≥1.0 g/dL mean Hb increase from baseline over a continuous 12-wk interval from Wks 13–24 in the absence of RBC transfusions. Secondary endpoints included proportion of pts who remained transfusion free over Wks 1–24, who achieved mean Hb increase of ≥1.5 g/dL from baseline to Wks 13–24, and mean change in NTD β-thalassemia pt-reported outcome tiredness and weakness (NTDT-PRO T/W) domain scores (higher scores reflect worse QoL).

Results
145 pts were randomized: 96 received luspatercept and 49 received PBO. Median age was 40.0 years (range 18.0–71.0); 41.7% were male. Baseline median Hb was 8.2 g/dL (range 5.3–10.1); median NTDT-PRO T/W score was 4.3 (range 0–9.5). 20 (13.8%) pts received RBC transfusions (max 5 units) in the 24 wks prior to treatment.

74 of 96 (77.1%) pts in the luspatercept arm achieved the primary endpoint vs 0 of 49 PBO pts (P<0.0001; Fig. A). The primary endpoint was achieved by 40 of 55 (72.7%) luspatercept pts with mean baseline Hb <8.5 g/dL (vs 0 PBO; P<0.0001), and 34 of 41 (82.9%) with mean baseline Hb ≥8.5 g/dL (vs 0 PBO; P<0.0001).


At Wks 13–24, 50 of 96 (52.1%) pts in the luspatercept arm achieved mean Hb increase of ≥1.5 g/dL compared to baseline vs 0 PBO (P<0.0001; Fig. A). 89.6% of pts in the luspatercept arm remained transfusion free at Wks 1–24 vs 67.3% PBO pts (P=0.0013). Change from baseline in NTDT-PRO T/W scores in luspatercept vs PBO arms were −0.92 vs −0.47 (least squares mean difference [LSMD] −0.48, P=0.0924) at Wks 13–24 and −1.00 vs −0.16 (LSMD −0.79, P=0.051) at Wks 37–48, respectively. Similar changes were also observed in the subset of luspatercept pts with mean baseline Hb <8.5 g/dL (LSMD at Wks 13–24 luspatercept vs PBO −0.73, P=0.0433). Improvement in NTDT-PRO T/W scores correlated with Hb increase (Fig. B).


Treatment-emergent adverse events (≥1, grade ≥3) were reported in 27 (28.1%) and 12 (24.5%) pts in luspatercept and PBO arms. Malignant events were only reported in the PBO arm, affecting 2 (4.1%) pts (diffuse large B-cell lymphoma, hepatocellular carcinoma). No thromboembolic or thrombophlebitis events were reported in either arm.

Conclusion
Treatment with luspatercept resulted in significant improvements of anemia, as measured by Hb levels, vs PBO in adults with NTD β-thalassemia. Changes in NTDT-PRO T/W correlated with increases in Hb. Luspatercept was well tolerated in this pt population.

Keyword(s): Anemia, Beta thalassemia, Clinical trial, Quality of life

This abstract is embargoed until Friday, June 11, 09:00 CEST

Presentation during EHA2021: The Presidential Symposium will be held on Friday, June 11, 2021 (16:00 - 17:30 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S101

Type: Presidential Symposium

Session title: Presidential Symposium

Background
β-thalassemia is an inherited hemoglobinopathy characterized by ineffective erythropoiesis and impaired red blood cell (RBC) maturation. Patients (pts) with non-transfusion dependent (NTD) β-thalassemia develop chronic anemia and other serious complications affecting survival and quality of life (QoL). Luspatercept, a first-in-class erythroid maturation agent approved by the EMA for treatment of anemia in adults with transfusion-dependent β-thalassemia, may have potential clinical benefit for NTD pts.

Aims
We report results of BEYOND, a phase 2, double-blind, randomized, multicenter study to determine the efficacy and safety of luspatercept vs placebo (PBO) in adults with NTD β-thalassemia (NCT03342404).

Methods
Eligible pts provided informed consent, were ≥18 years with β-thalassemia or hemoglobin (Hb) E/β-thalassemia and received ≤5 RBC units in the 24 weeks (wks) prior to randomization, with mean baseline Hb ≤10.0 g/dL. Pts were randomized 2:1 to receive luspatercept 1 mg/kg (titration up to 1.25 mg/kg) or PBO subcutaneously every 3 wks for ≥48 wks. Pts in both arms continued to receive best supportive care, including sporadic RBC transfusions and iron chelation therapy.

The primary endpoint was achievement of ≥1.0 g/dL mean Hb increase from baseline over a continuous 12-wk interval from Wks 13–24 in the absence of RBC transfusions. Secondary endpoints included proportion of pts who remained transfusion free over Wks 1–24, who achieved mean Hb increase of ≥1.5 g/dL from baseline to Wks 13–24, and mean change in NTD β-thalassemia pt-reported outcome tiredness and weakness (NTDT-PRO T/W) domain scores (higher scores reflect worse QoL).

Results
145 pts were randomized: 96 received luspatercept and 49 received PBO. Median age was 40.0 years (range 18.0–71.0); 41.7% were male. Baseline median Hb was 8.2 g/dL (range 5.3–10.1); median NTDT-PRO T/W score was 4.3 (range 0–9.5). 20 (13.8%) pts received RBC transfusions (max 5 units) in the 24 wks prior to treatment.

74 of 96 (77.1%) pts in the luspatercept arm achieved the primary endpoint vs 0 of 49 PBO pts (P<0.0001; Fig. A). The primary endpoint was achieved by 40 of 55 (72.7%) luspatercept pts with mean baseline Hb <8.5 g/dL (vs 0 PBO; P<0.0001), and 34 of 41 (82.9%) with mean baseline Hb ≥8.5 g/dL (vs 0 PBO; P<0.0001).


At Wks 13–24, 50 of 96 (52.1%) pts in the luspatercept arm achieved mean Hb increase of ≥1.5 g/dL compared to baseline vs 0 PBO (P<0.0001; Fig. A). 89.6% of pts in the luspatercept arm remained transfusion free at Wks 1–24 vs 67.3% PBO pts (P=0.0013). Change from baseline in NTDT-PRO T/W scores in luspatercept vs PBO arms were −0.92 vs −0.47 (least squares mean difference [LSMD] −0.48, P=0.0924) at Wks 13–24 and −1.00 vs −0.16 (LSMD −0.79, P=0.051) at Wks 37–48, respectively. Similar changes were also observed in the subset of luspatercept pts with mean baseline Hb <8.5 g/dL (LSMD at Wks 13–24 luspatercept vs PBO −0.73, P=0.0433). Improvement in NTDT-PRO T/W scores correlated with Hb increase (Fig. B).


Treatment-emergent adverse events (≥1, grade ≥3) were reported in 27 (28.1%) and 12 (24.5%) pts in luspatercept and PBO arms. Malignant events were only reported in the PBO arm, affecting 2 (4.1%) pts (diffuse large B-cell lymphoma, hepatocellular carcinoma). No thromboembolic or thrombophlebitis events were reported in either arm.

Conclusion
Treatment with luspatercept resulted in significant improvements of anemia, as measured by Hb levels, vs PBO in adults with NTD β-thalassemia. Changes in NTDT-PRO T/W correlated with increases in Hb. Luspatercept was well tolerated in this pt population.

Keyword(s): Anemia, Beta thalassemia, Clinical trial, Quality of life

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