Department of Malignant Hematology
Contributions
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 16:45 to 13.06.2015 17:00
Location: Room C1
Background
Anemia, a hallmark of MDS, is challenging to treat, particularly after failure of erythropoiesis-stimulating agents (ESAs). Sotatercept (ACE-011) is a novel and first-in-class activin type IIA receptor fusion protein that acts on late-stage erythropoiesis to increase release of mature erythrocytes into circulation (Carrancio S, et al. Br J Haematol 2014;165:870-82).
Aims
This phase 2, open-label, dose-finding study aims to determine a safe, tolerable, and effective dose of sotatercept in anemic pts with lower-risk MDS.
Methods
The primary endpoint was erythroid hematological improvement (HI-E; modified International Working Group 2006 criteria). Secondary endpoints included rate of RBC transfusion independence (TI) ≥ 8 weeks and safety. Eligible pts had International Prognostic Scoring System-defined Low or Intermediate-1-risk MDS (Greenberg P, et al. Blood 1997;89:2079-88) and anemia, with no response, loss of response, or low chance of response to ESAs. Pts received subcutaneous sotatercept at 0.1, 0.3, 0.5, 1.0, or 2.0 mg/kg every 3 weeks for up to 8 doses; pts with clinical benefit may receive treatment beyond 8 doses until meeting protocol discontinuation criteria. Informed consent was obtained from all pts. ClinicalTrials.gov identifier: NCT01736683.
Results
As of February 4, 2015, a total of 59 MDS pts were enrolled: 7, 6, 21, 20, and 5 in the 0.1, 0.3, 0.5, 1.0, and 2.0 mg/kg groups, respectively. Overall, 66% of pts were male, median age was 71 years, and median time from diagnosis 4 years. Pts received a median 6 RBC units (range 0–16) in the 8 weeks prior to treatment; 50 (85%) received ≥ 4 RBC units (high transfusion burden; HTB) and 9 (15%) received < 4 RBC units (low transfusion burden; LTB). In this heavily pre-treated cohort, 56 (95%) pts were previously treated with ESAs, 31 (53%) with hypomethylating agents, 27 (46%) with lenalidomide, and 26 (44%) with other MDS treatments.
Of 53 pts evaluable for efficacy, 23 (43%) achieved HI-E: 0 of 7 (0%), 4 of 6 (67%), 9 of 20 (45%), and 10 of 20 (50%) pts in the 0.1, 0.3, 0.5, and 1.0 mg/kg groups, respectively. Review of efficacy data for the 2.0 mg/kg dose group is ongoing. Of 45 evaluable HTB pts, 6 (13%) achieved RBC-TI ≥ 8 weeks; median duration of longest response was 67.5 days, 107 days, and 122.5 days in the 0.3, 0.5, and 1.0 mg/kg dose groups, respectively. Of 8 evaluable LTB pts, 5 (63%) achieved RBC-TI ≥ 8 weeks and a mean hemoglobin increase of ≥ 1.5 g/dL sustained for ≥ 8 weeks; duration of RBC-TI for responders ranged from 175–472+ days.
Sotatercept was generally well tolerated. The most common adverse events (AEs), all grades, were asthenia/fatigue (n = 24), peripheral edema (n = 12), and diarrhea (n = 12). Eighteen (31%) pts had ≥ 1 grade 3 or 4 AE; of these, 3 (5%) were reported as suspected to be study drug-related (1 each with grade 3 pain in extremity, grade 3 hypertension, and grade 4 acute myeloid leukemia, all in the 0.5 mg/kg dose group). Overall, 4 pts discontinued due to suspected treatment-related AEs: 1 each with grade 2 hemolytic anemia, grade 2 hypertension, grade 2 muscular weakness, and grade 2 increased blood pressure with grade 2 diarrhea in the 0.3, 0.5, 1.0, and 2.0 mg/kg groups, respectively.
Summary
Data from this ongoing study suggest sotatercept was well tolerated, with promising evidence of clinical activity in this cohort of heavily pre-treated, anemic, lower-risk MDS pts who had failed or were refractory to prior ESAs.
PF and AFL contributed equally to this abstract as senior co-authors.
Keyword(s): Anemia, Clinical trial, Erythropoieisis, MDS
Session topic: MDS Clinical
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 16:45 to 13.06.2015 17:00
Location: Room C1
Background
Anemia, a hallmark of MDS, is challenging to treat, particularly after failure of erythropoiesis-stimulating agents (ESAs). Sotatercept (ACE-011) is a novel and first-in-class activin type IIA receptor fusion protein that acts on late-stage erythropoiesis to increase release of mature erythrocytes into circulation (Carrancio S, et al. Br J Haematol 2014;165:870-82).
Aims
This phase 2, open-label, dose-finding study aims to determine a safe, tolerable, and effective dose of sotatercept in anemic pts with lower-risk MDS.
Methods
The primary endpoint was erythroid hematological improvement (HI-E; modified International Working Group 2006 criteria). Secondary endpoints included rate of RBC transfusion independence (TI) ≥ 8 weeks and safety. Eligible pts had International Prognostic Scoring System-defined Low or Intermediate-1-risk MDS (Greenberg P, et al. Blood 1997;89:2079-88) and anemia, with no response, loss of response, or low chance of response to ESAs. Pts received subcutaneous sotatercept at 0.1, 0.3, 0.5, 1.0, or 2.0 mg/kg every 3 weeks for up to 8 doses; pts with clinical benefit may receive treatment beyond 8 doses until meeting protocol discontinuation criteria. Informed consent was obtained from all pts. ClinicalTrials.gov identifier: NCT01736683.
Results
As of February 4, 2015, a total of 59 MDS pts were enrolled: 7, 6, 21, 20, and 5 in the 0.1, 0.3, 0.5, 1.0, and 2.0 mg/kg groups, respectively. Overall, 66% of pts were male, median age was 71 years, and median time from diagnosis 4 years. Pts received a median 6 RBC units (range 0–16) in the 8 weeks prior to treatment; 50 (85%) received ≥ 4 RBC units (high transfusion burden; HTB) and 9 (15%) received < 4 RBC units (low transfusion burden; LTB). In this heavily pre-treated cohort, 56 (95%) pts were previously treated with ESAs, 31 (53%) with hypomethylating agents, 27 (46%) with lenalidomide, and 26 (44%) with other MDS treatments.
Of 53 pts evaluable for efficacy, 23 (43%) achieved HI-E: 0 of 7 (0%), 4 of 6 (67%), 9 of 20 (45%), and 10 of 20 (50%) pts in the 0.1, 0.3, 0.5, and 1.0 mg/kg groups, respectively. Review of efficacy data for the 2.0 mg/kg dose group is ongoing. Of 45 evaluable HTB pts, 6 (13%) achieved RBC-TI ≥ 8 weeks; median duration of longest response was 67.5 days, 107 days, and 122.5 days in the 0.3, 0.5, and 1.0 mg/kg dose groups, respectively. Of 8 evaluable LTB pts, 5 (63%) achieved RBC-TI ≥ 8 weeks and a mean hemoglobin increase of ≥ 1.5 g/dL sustained for ≥ 8 weeks; duration of RBC-TI for responders ranged from 175–472+ days.
Sotatercept was generally well tolerated. The most common adverse events (AEs), all grades, were asthenia/fatigue (n = 24), peripheral edema (n = 12), and diarrhea (n = 12). Eighteen (31%) pts had ≥ 1 grade 3 or 4 AE; of these, 3 (5%) were reported as suspected to be study drug-related (1 each with grade 3 pain in extremity, grade 3 hypertension, and grade 4 acute myeloid leukemia, all in the 0.5 mg/kg dose group). Overall, 4 pts discontinued due to suspected treatment-related AEs: 1 each with grade 2 hemolytic anemia, grade 2 hypertension, grade 2 muscular weakness, and grade 2 increased blood pressure with grade 2 diarrhea in the 0.3, 0.5, 1.0, and 2.0 mg/kg groups, respectively.
Summary
Data from this ongoing study suggest sotatercept was well tolerated, with promising evidence of clinical activity in this cohort of heavily pre-treated, anemic, lower-risk MDS pts who had failed or were refractory to prior ESAs.
PF and AFL contributed equally to this abstract as senior co-authors.
Keyword(s): Anemia, Clinical trial, Erythropoieisis, MDS
Session topic: MDS Clinical