Lenalidomide Safety/Efficacy in Myelodysplastic Syndromes (MDS) Associated With a Deletion (Del)(5q) Cytogenetic Abnormality

Counts of study participants who had adverse events (AEs) during the study. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. Adverse events were evaluated by the investigator.

The National Cancer Institute (NCI)'s Common Toxicity Criteria for AEs (NCI CTC) was used to grade AE severity. Severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE.

A participant was categorized as having a transfusion reduction response if there was a ≥ 50% decrease from pretreatment transfusion requirements (before the start of the study mediation) compared to any consecutive 56 days during the study (i.e. post treatment).

Transfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Time to transfusion independence was defined as the day of the first dose of study drug to the first day of the first 56-day RBC transfusion-free period.

Transfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Participants who relapsed required a transfusion after the period of transfusion independence. Participants who maintained transfusion independence did not require a transfusion during the remainder of the study.

Duration of response is measured from the first of the consecutive 56 days during which the participant was free of RBC transfusions to the date of the first RBC transfusion after this period. Duration of response was censored at the date of last visit for participants who maintained transfusion independence.

The change from baseline in hemoglobin for participants who became RBC-transfusion independent. The maximum hemoglobin value obtained during the response period is used in the calculation of change from baseline.

Participants deemed evaluable by the central cytogenetic review had their cytogenetic response categorized as major or minor. A major cytogenetic response was defined as ≥ 20 metaphases recorded at baseline, and at least

1 post baseline evaluation with ≥ 20 metaphases analyzed with no abnormal metaphases observed. A minor cytogenetic response was defined as ≥ 20 metaphases analyzed at baseline, and at least 1 post baseline evaluation with ≥ 20 metaphases analyzed with a ≥ 50% reduction in the proportion of hematopoietic cells with cytogenetic abnormalities compared with baseline.

Major platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3 in all values within 56 days of start of treatment, an absolute increase of ≥30,000/mm^3 sustained for ≥56 consecutive days. In platelet transfusion-dependent participants, a major response was stabilization of platelet counts and platelet transfusion independence.

Minor platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3, a ≥ 50% increase in platelet count with a net increase >10,000/mm^3 for a consecutive 56-day period in the absence of platelet transfusions.

Major neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3 in all values obtained within 56 days of start of treatment, a ≥ 100% increase or an absolute increase of

≥ 500/mm^3, whichever was greater (at least to be ≥ 500/mm^3), sustained for 56 consecutive days. Minor neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3, an increase in ANC concentration of ≥ 100% sustained for 56 consecutive days.

Bone marrow aspirates were assessed by a central reviewer. A complete bone marrow improvement required a baseline French-American-British (FAB) classification (see Baseline Characteristics) of refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB) or chronic myelomonocytic leukemia (CMML) and a during study assessment of no MDS. A partial bone marrow improvement reflected an improved FAB classification compared to baseline (e.g. RARS to RA) but evidence of MDS continued to exist.

Bone marrow aspirate was assessed by a central reviewer. Progression is represented in two categories according to changes from baseline in French-American-British (FAB) classification (see Baseline Characteristics):

• Baseline classification of refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) to a during treatment (plus 30 days) classification of refractory anemia with excess blasts (RAEB).
• Any baseline FAB classification to a during treatment (plus 30 days) classification of acute myeloid leukemia (AML).