Contributions
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
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