Extension Study to Evaluate Long-Term Effects of Luspatercept in Patients With Myelodysplastic Syndromes (MDS) (A536-05/MK-6143-003)

An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who experienced an AE was reported.

An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who discontinued luspatercept due to an AE was reported.

The mHI-E was defined as a mean hemoglobin (Hgb) increase ≥1.5 g/dL over an 8-week period as compared to baseline, not influenced by red blood cell (RBC) transfusion in low transfusion burden (LTB) participants and a decrease of ≥4 units or ≥50% of units of RBCs transfused over a period of 8 weeks, relative to the number of units of RBCs transfused in the 8 weeks immediately prior to baseline in high transfusion burden (HTB) participants. LTB participants were those who received <4 units of RBCs within 8 weeks prior to baseline. HTB participants were those who required a transfusion of ≥4 units of RBCs in the 8 weeks prior to baseline. Rolling 8 weeks was defined as any consecutive 8 weeks during the study.

Per IWG 2006 response criteria, the rate of HI-E was defined as the percentage of participants with an HI-E response by an Hgb increase of ≥1.5 g/dL for participants not transfused or as defined by having received less than 4 units of RBCs within 8 weeks of baseline or reduction by ≥4 units of RBCs transfused (for a Hgb≤9.0 g/dL) during any 8-week period on study, compared with the 8-week period prior to study day 1.

Per IWG 2006 response criteria, HI-N response was defined for participants with baseline absolute neutrophil count (ANC) <1.0×10^9/L as the percentage increase ≥100% and an absolute mean increase >0.5 ×10^9/L during any rolling 8-week window on treatment compared with baseline. The rolling 8-week was defined as any consecutive 8 weeks during the study. Percentage of participants with HI-N response were reported.

Per IWG 2006 response criteria, HI-P response was defined for participants with baseline platelet count <100×10^9/L as the following: 1) For participants with baseline ≥20×10^9/L, an absolute increase of ≥30×10^9/L during any rolling 8-week window on treatment and 2) For participants with baseline <20×10^9/L, mean value of >20×10^9/L and percentage increase ≥100% during any rolling 8-week window on treatment. The rolling 8-week was defined as any consecutive 8 weeks during the study. Percentage of participants with HI-P response were reported.

For LTB participants, HI-E was defined as all Hgb increase ≥1.5 g/dL during any rolling 8 weeks window. LTB participants were those who received <4 units of RBCs within 8 weeks prior to baseline. Per IWG 2006 response criteria, duration of HI-E was defined as the time from the first day of the first rolling 8 weeks interval of showing response to the last day of the last consecutive rolling 8 weeks interval of showing response. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. When there were multiple disjointed intervals with response, the longest interval was used.

For HTB participants, HI-E was defined as RBC transfusion reduction ≥4 units during any rolling 8 weeks. HTB participants were those who required a transfusion of ≥4 units of RBCs in the 8 weeks prior to baseline. Per IWG 2006 response criteria, duration of HI-E was defined as the time from the first day of the first rolling 8 weeks interval of showing response to the last day of the last consecutive rolling 8 weeks interval of showing response. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. When there were multiple disjointed intervals with response, the longest interval was used.

For LTB participants, HI-E was defined as all Hgb increase ≥1.5 g/dL during any rolling 8 weeks window. LTB participants were those who received <4 units of RBCs within 8 weeks prior to baseline. Per IWG 2006 response criteria, time to HI-E was defined as the first date of the rolling 8 weeks interval of showing response minus first dose date plus 1. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. When there were multiple disjointed intervals with response, the longest interval was used.

For HTB participants, HI-E was defined as RBC transfusion reduction ≥4 units during any rolling 8 weeks. HTB participants were those who required a transfusion of ≥4 units of RBCs in the 8 weeks prior to baseline. Per IWG 2006 response criteria, time to HI-E was defined as the first date of the rolling 8 weeks interval of showing response minus first dose date plus 1. Rolling 8 weeks was defined as any consecutive 8 weeks during the study.

Per protocol, RBC-TI response was defined as not requiring RBC transfusion for 8 or more weeks while on treatment among participants with ≥2 units of RBC transfusions at baseline. The rate of RBC-TI was defined as the percentage of participants with ≥2 units of RBC transfusions at baseline with RBC-TI.

RBC TB was defined as ≥4 units or 50% reduction during rolling 8 weeks among HTB participants. The rolling 8-week was defined as any consecutive 8 weeks during the study. HTB participants are those who required a transfusion of ≥4 units of RBCs in the 8 weeks prior to baseline. Mean change from baseline to Week 8 in reduction in RBC TD in HTB participants was reported.

Baseline hemoglobin levels were the documented pre-transfusion hemoglobin values during the 12 weeks prior to treatment. LTB participants were those who received <4 units of RBCs within 8 weeks prior to baseline. Mean change from baseline to Week 8 in hemoglobin levels ≥1.5 grams/dL in LTB participants were reported.

Blood samples were collected at pre-determined time points to determine the serum concentration of luspatercept. Serum concentrations that were below the limit of quantitation (LOQ) of the assay prior to the first dose were assigned a numerical value of zero. Post-treatment serum concentrations that were below the LOQ of the assay were treated as missing. Serum concentrations assigned a value of missing were omitted from the analysis. The LOQ of the assay was 50 ng/mL.

Blood samples were collected at pre-specified time intervals to determine serum iron concentration. The percentage change from baseline to Day 1853 in concentration of serum iron was reported.

Blood samples were collected at pre-specified time intervals to determine TIBC. The percentage change from baseline to Day 1853 in TIBC was reported.

Blood samples were collected at pre-specified time intervals to determine serum transferrin concentration. The percentage change from baseline to Day 1853 in concentration of transferrin was reported.

Blood samples were collected at pre-specified time intervals to determine soluble transferrin receptor concentration. The percentage change from baseline to Day 1853 in concentration of soluble transferrin receptor was reported.

Blood samples were collected at pre-specified time intervals to determine serum ferritin concentration. The percentage change from baseline to Day 1853 in concentration of serum ferritin was reported.

Blood samples were to be collected at pre-specified time intervals to determine concentration of NTBI. Baseline was prespecified to be the last measurement prior to the first dose of study drug.

Blood samples were to be collected at pre-specified time intervals to determine concentration of serum hepcidin. Baseline was prespecified to be the last measurement prior to the first dose of study drug.

Blood samples were collected at pre-specified time intervals to determine serum erythropoietin concentration. The percentage change from baseline to Day 1853 in concentration of serum erythropoietin was reported.

Blood samples were collected at pre-specified time intervals to determine reticulocyte count. The percentage change from baseline to Day 1853 in reticulocyte count was reported.

Blood samples were to be collected at pre-specified time intervals to determine nRBC. Baseline was prespecified to be the last measurement prior to the first dose of study drug.

Blood samples were collected at pre-specified time intervals to determine serum direct bilirubin concentration. The percentage change from baseline to Day 1853 in concentration of direct bilirubin was reported.

Blood samples were collected at pre-specified time intervals to determine total bilirubin concentration. The percentage change from baseline to Day 1853 in concentration of total bilirubin was reported.

Blood samples were collected at pre-specified time intervals to determine serum lactate dehydrogenase level. The percentage change from baseline to Day 1853 in concentration of lactate dehydrogenase level was reported.

Blood samples were to be collected at pre-specified time intervals to determine BSAP. Baseline was prespecified to be the last measurement prior to the first dose of study drug.

Blood samples were to be collected at pre-specified time intervals to determine CTX. Baseline was prespecified to be the last measurement prior to the first dose of study drug.