LBH589 Alone or in Combination With Erythropoietin Stimulating Agents (ESA) in Patients With Low or Int-1 Risk Myelodysplastic Syndromes (MDS)

HI-E was assessed according to the modified international working group (IWG) criteria for HI. Erythroid response (pretreatment, \<11 g/dL): Hgb increase by ≥ 1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk, and only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response evaluation; Platelet response (pretreatment, \< 100 x 109/L): absolute increase of ≥ 30 x 109/L for participants starting with \> 20 x 109/L and platelets Increase from \< 20 x 109/L to \> 20 x 109/L and by at least 100%; Neutrophil response (pretreatment, \< 1.0 x 109/L): at least 100% increase and an absolute increase \> 0.5 x 109/L; Progression or relapse after HI: At least 1 of the following: At least 50% decrement from maximum response levels in granulocytes or platelets, reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.

Time frame: 16 weeks

Population: Participants from the core phase, who had valid response data, were analyzed.

DFS was defined as the time from start of treatment to the time to relapse.

Time frame: 52 weeks

Population: DFS could not be evaluated because there was no disease-free period.

EFS was defined as the time from start of treatment to failure or death from any cause.

Time frame: 52 weeks

Population: Event-free survival could not be evaluated because there was no response, no progression or no disease-free period.

The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast \<5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex \>= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high \>=2.5 points (6 months of median survival).

Time frame: baseline

Population: All participants from the core phase were analyzed.

The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast \<5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex \>= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high \>=2.5 points (6 months of median survival).

Time frame: 52 weeks

Population: Only participants from the randomized phase, who had values at week 52, were included in the analysis.

The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast \<5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex \>= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high \>=2.5 points (6 months of median survival).

Time frame: baseline

Population: All participants from the core phase were analyzed.

The IPSS score values were calculated based on the results of bone marrow analysis. A score value of 0 has bone marrow blast \<5%, karyotype of normal, sole: -Y, del 5Q, del 20q and cytopenias (lineages affected) of 0 to 1. Score value of 0.5 has 5-10 bone marrow blasts, karyotype of Others and cytopenias of 2 to 3. A score value of 1.0 has complex \>= 3 chromosomal abnormalities and/or chromosome 7 anomalies. A score of 1.5 has 11-20 bone marrow blasts and a score of 2.0 has 21-30 bone marrow blasts. The prognostic score is determined by the sum of the single scoring values. The risk groups are determined as follows: Low = 0 points (5.7 years of median survival); intermediate -1 (INT-1) = 0.5-1.0 points (3.5 years of median survival); INT-2 = 1.5-2.0 points (1.2 years of median survival); and high \>=2.5 points (6 months of median survival).

Time frame: 52 weeks

Population: Participants from the randomized phase, who had values at week 52, were included in the analysis.

OS was defined as the time from start of treatment to death from any cause.

Time frame: 48 weeks

Population: All participants from the core phase were analyzed.

HI-E was assessed according to the modified international working group (IWG) criteria for HI. Erythroid response (pretreatment, \<11 g/dL): Hgb increase by ≥ 1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk, and only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response evaluation; Platelet response (pretreatment, \< 100 x 109/L): absolute increase of ≥ 30 x 109/L for participants starting with \> 20 x 109/L and platelets Increase from \< 20 x 109/L to \> 20 x 109/L and by at least 100%; Neutrophil response (pretreatment, \< 1.0 x 109/L): at least 100% increase and an absolute increase \> 0.5 x 109/L; Progression or relapse after HI: At least 1 of the following: At least 50% decrement from maximum response levels in granulocytes or platelets, reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.

Time frame: 32 weeks, 52 weeks

Population: Participants from the randomized phase, who had valid response data, were analyzed.

Objective response (complete remission (CR) + partial remission (PR) and HI-platelet (HI-P) response + HI-neutrophil (HI-N) response) was assessed according to the modified IWG criteria: CR bone marrow with 5% myeloblasts with normal maturation of al cell lines (persistent dysplasia is noted) and peripheral blood with Hgb \>= 11 g/dL platelets \>=100 X 10\^9/L, neutrophils \>= 1.0 x 10\^9/L and blasts 0%. PR = All CR if abnormal before treatment except bone marrow blasts decreased by\>=50% over pretreatment but still \>5% (ellularity and morphology not relevant). HI-P (pretreatment, \< 100 x 109/L) = absolute increase of ≥ 30 x 109/L for participants starting with \> 20 x 109/L and platelets Increase from \< 20 x 109/L to \> 20 x 109/L and by at least 100%; HI-N (pretreatment, \< 1.0 x 109/L) = at least 100% increase and an absolute increase \> 0.5 x 10\^9/L.

Time frame: 16 weeks

Population: Participants from the core phase, who had valid data, were analyzed.

Objective response (complete remission (CR) + partial remission (PR) and HI-platelet (HI-P) response + HI-neutrophil (HI-N) response) was assessed according to the modified IWG criteria: CR bone marrow with 5% myeloblasts with normal maturation of al cell lines (persistent dysplasia is noted) and peripheral blood with Hgb \>= 11 g/dL platelets \>=100 X 10\^9/L, neutrophils \>= 1.0 x 10\^9/L and blasts 0%. PR = All CR if abnormal before treatment except bone marrow blasts decreased by\>=50% over pretreatment but still \>5% (ellularity and morphology not relevant). HI-P (pretreatment, \< 100 x 109/L) = absolute increase of ≥ 30 x 109/L for participants starting with \> 20 x 109/L and platelets Increase from \< 20 x 109/L to \> 20 x 109/L and by at least 100%; HI-N (pretreatment, \< 1.0 x 109/L) = at least 100% increase and an absolute increase \> 0.5 x 10\^9/L.

Time frame: 32 weeks, 48 weeks

Population: Participants from the randomized phase, who had valid data, were analyzed.

PFS was defined as the time from start of treatment to disease progression or death from MDS.

Time frame: 52 weeks

Population: PFS could not be evaluated because there was no progression.

Time to cause-specific death was defined as the time from start of treatment to death related to MDS.

Time frame: 52 weeks

Population: Time to cause-specific death could not be evaluated because there was no cause-specific death.

Time to response was defined as the time from start of treatment to the first documented response (complete \[CR\] or partial \[PR\]) according to modified IWG criteria for HI.

Time frame: 52 weeks

Population: Time to response could not be evaluated because there was no response.