Tamibarotene Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome

CR was determined by the investigator per the modified International Working Group Myelodysplastic Syndrome (IWG MDS). CR was defined as participants with hemoglobin ≥11 grams/deciliter (g/dL), neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, bone marrow blasts (BMBs) ≤5% and normal maturation of all cell lines, persistent dysplasia were noted.

Time frame: Up to 45 months

Population: The mITT analysis set included the first approximately 190 randomized participants.

HRQoL was evaluated by EORTC QLQ-C30 global health status/quality of life composite scale in all randomized participants. The QLQ-30 is a cancer-specific, self-administered questionnaire that contains 30 questions, covering global, functional, and symptom scales. Scores range from 0 to 100. Higher scores on global and functional scales indicated better quality of life (QoL), while higher scores on the symptom scales indicated declining QoL.

Time frame: Up to 45 months

Population: While the QLQ-30 questionnaire was completed to derive data for the planned EORTC QLQ-30 outcome measure, the study was terminated prior to that data from the questionnaire were collected, analyzed, summarized, or made available by the study sponsor. Therefore, no questionnaire data can be presented here.

The EQ-5D-3L essentially consisted of- the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprised of the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 3 levels: no problems, some problems, extreme problems. Total scale range for each dimension reported was 1 to 3. The EQ VAS recorded the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This information can be used as a quantitative measure of health outcome as judged by the individual respondents. Total scale range for VAS dimension reported was 0 to 100.

Time frame: Up to 45 months

Population: While the Q-5D-3L questionnaire was completed to derive data for the planned EuroQoL-5D outcome measure, the study was terminated prior to that data from the questionnaire were collected, analyzed, summarized, or made available by the study sponsor. Therefore, no questionnaire data can be presented here.

DOCR was defined as the duration from the date of first documented evidence of CR to the date of documented relapse of disease or disease progression, as determined by the investigator per the modified IWG MDS criteria, or death due to any cause, whichever occurred first. CR was defined as participants with hemoglobin ≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, BMBs ≤5% and normal maturation of all cell lines, persistent dysplasia were noted. Among CR responders, DOCR was calculated as: DOCR (months) = (first date of documented relapse of disease, disease progression, or death due to any cause - date of first documented evidence of CR + 1) / 30.4375.

Time frame: Up to 45 months

Population: The mITT analysis set included the first approximately 190 randomized participants. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.

DOR: duration from date of first documented evidence of CR, partial remission (PR), marrow CR (mCR), or hematologic improvement (HI) to date of documented disease progression or relapse of disease as determined by investigator per modified IWG MDS criteria or death due to any cause, whichever occurred first. CR: hemoglobin (Hb)≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, BMBs≤5% & normal maturation of all cell lines, persistent dysplasia. PR: Hb ≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, BMBs decreased by ≥50% from baseline, but \>5%. mCR: Hb ≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, BMBs decreased by≥50% from baseline, & ≤5%. Subcategories of HI included erythroid response (Hgb increase by ≥1.5 g/dL), platelet response (absolute increase of≥30\*10\^9/L if starting with \>20\*10\^9/L platelets; increase from \<20 to \>20\*10\^9/L and by ≥100%),neutrophil response (≥100% increase & absolute increase \>0.5\*10\^9/L).

Time frame: Up to 45 months

Population: The mITT analysis set included the first approximately 190 randomized participants. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.

TI was defined as a period of at least 56 days with no red blood cell (RBC) or platelet transfusion since the date of randomization to the last dose of study drug + 30 days, the initiation of post-treatment therapy, or death, whichever occurred first.

Time frame: Up to 45 months

Population: The mITT analysis set included the first approximately 190 randomized participants.

An AE was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. TEAEs are defined as those AEs with onset after the first dose of study drug or existing events that worsened after the first dose during the study up until the last dose of study drug + 30 days. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Time frame: Up to 45 months

Population: Adverse Event data were collected for the Safety Analysis Set 1 and included all participants who were randomized and had received any amount of study drug (tamibarotene, placebo, or azacitidine); Adverse Event data were collected by dose level received.

OR: Participants who achieved CR, PR, mCR, or subcategories of HI, as determined by investigator per modified IWG MDS criteria. CR was defined as hemoglobin ≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, bone marrow blasts (BMBs) ≤5% and normal maturation of all cell lines, persistent dysplasia were noted. PR was defined as hemoglobin ≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, BMBs decreased by ≥50% from baseline, but \>5%. mCR was defined as hemoglobin ≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, BMBs decreased by ≥50% from baseline, and ≤5%. Subcategories of HI included erythroid response (Hgb increase by ≥1.5 g/dL), platelet response (absolute increase of ≥30\*10\^9 /L if starting with \>20\*10\^9/L platelets increase from \<20\*10\^9/L to \>20\*10\^9/L and by at least 100%), neutrophil response (at least a 100% increase and an absolute increase \>0.5\*10\^9 /L).

Time frame: Up to 45 months

Population: The mITT analysis set included the first approximately 190 randomized participants.

TCR was defined as the duration from the date of randomization to the date of the first documented evidence of CR as determined by the investigator per the modified IWG MDS criteria. Among CR responders, this outcome measure was calculated as: Time to CR= (date of the first documented evidence of CR - date of randomization + 1) / 30.4375. CR was defined as hemoglobin ≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, bone marrow blasts ≤5% and normal maturation of all cell lines, persistent dysplasia were noted.

Time frame: Up to 45 months

Population: The mITT analysis set included the first approximately 190 randomized participants. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.

TIR: duration from date of randomization to the date of first documented evidence of CR, PR, mCR, or HI as determined by investigator per modified IWG MDS criteria. CR: hemoglobin (Hb) ≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, bone marrow blasts (BMBs) ≤5% and normal maturation of all cell lines, persistent dysplasia. PR: Hb ≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, BMBs decreased by ≥50% from baseline, but \>5%. mCR: Hb ≥11 g/dL, neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, BMBs decreased by ≥50% from baseline, and ≤5%. Subcategories of HI included erythroid response (Hgb increase by ≥1.5 g/dL), platelet response (absolute increase of ≥30\*10\^9/L if starting with \>20\*10\^9/L platelets increase from \<20 to \>20\*10\^9/L and by at least 100%), neutrophil response (at least a 100% increase and absolute increase\>0.5\*10\^9 /L).

Time frame: Up to 45 months

Population: The mITT analysis set included the first approximately 190 randomized participants. Here, overall number of participants analyzed signifies those who were evaluable for this outcome measure.