Scientific programme

OS03  Oral Session

06-May-2017 08:30 10:00

Background: Anemia represents a common therapeutic challenge in myelodysplastic syndromes (MDS). Many patients are offered erythropoiesis-stimulating agents (ESAs), yet response rates and duration are suboptimal. Luspatercept (ACE-536), a fusion protein containing modified activin receptor type IIB, is being developed for treatment of anemia in lower-risk MDS. Luspatercept binds TGF-β superfamily ligands including GDF11 and activin B to promote late-stage erythroid differentiation and increase hemoglobin levels (Suragani R, Nat Med, 2014 and Attie K, Am J Hematol, 2014). A Phase 3 study of luspatercept in regularly transfused ring-sideroblast positive [RS(+)] lower-risk MDS patients who are ESA-refractory or have EPO >200 U/L (MEDALIST study; NCT02631070) is ongoing. The current Phase 2 study has been expanded to include patient subgroups excluded from MEDALIST and may identify other lower-risk MDS subpopulations who could benefit from luspatercept.

Aims: This ongoing, Phase 2, multicenter, open-label study evaluates the effects of luspatercept in lower-risk MDS patients. Endpoints include erythroid response (IWG HI-E), RBC transfusion independence (RBC-TI, ≥8 weeks), duration of TI, pharmacodynamic biomarkers, and safety.

Methods: Inclusion criteria: MDS IPSS low/int-1, age ≥18 years, hemoglobin <10 g/dL (if <4U RBC/8 weeks), no prior HMA, and no current lenalidomide or ESA. The dose-escalation phase of the study has been completed. A new expansion cohort is currently being enrolled and includes patients with low transfusion burden (<4U RBC/8 weeks) and either 1) RS(+) (≥15% in bone marrow) and EPO ≤200 U/L or 2) RS(-) and any EPO level. Patients are treated every 3 weeks for up to 5 doses (titration allowed to 1.75 mg/kg) and are subsequently eligible for long-term treatment up to 5 additional years.

Results: Preliminary data were available for 64 patients treated for 3 months with ≥0.75 mg/kg as of 09Sept2016. RS(+) patients had HI-E response rates of 46% (EPO 200-500 U/L) and 62% (EPO <200 U/L) and rates of RBC-TI of 33% (EPO 200-500 U/L) and 68% (EPO <200 U/L). The majority of adverse events were grade 1/2, with 3 possibly/probably related grade 3/serious AEs as of 07Feb2017: blast cell count increase, myalgia, and worsening of general condition. Data from longer treatment duration and additional patients, including RS(-), will be presented at the meeting.

Conclusions: In lower-risk MDS, high erythroid response to luspatercept was seen in RS(+) patients, including those with EPO levels >200 U/L.  Encouraging preliminary results for RS(-) patients will be presented.

U. Platzbecker 1, U. Germing 2, K. Götze 3, P. Kiewe 4, T. Wolff 5, K. Mayer 6, J. Chromik 7, M. Radsak 8, D. Wilson 9, X. Zhang 9, A. Laadem 10, M. Sherman 9, K. Attie 9, P. Linde 9, A. Giagounidis 11
1Universitätsklinikum Carl Gustav Carus, -, Dresden, Germany
2Universitätsklinikum Düsseldorf, -, Düsseldorf, Germany
3III. Department of Medicine, Hematology and Medical Oncology- Technical University Munich- Klinikum rechts der Isar, Munich, Germany
4Onkologischer Schwerpunkt am Oskar-Helene-Heim, -, Berlin, Germany
5OncoResearch Lerchenfeld UG, -, Hamburg, Germany
6University Hospital Bonn, -, Bonn, Germany
7Universitätsklinikum Frankfurt- Goethe Universität, -, Frankfurt/Main, Germany
8Johannes Gutenberg-Universität, -, Mainz, Germany
9Acceleron Pharma, -, Cambridge- MA, USA
10Celgene Corporation, -, Summit- NJ, USA
11Marien Hospital Düsseldorf, -, Düsseldorf, Germany