Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an IDH1 Mutation

Overall Response (OR) rate per IWG 2023 criteria

Defined as CR (or CR equivalent) + PR + CRL + CRh + hematological improvement (HI)

Time frame: Through the end of the study (approximately 4 years)

Event-free survival (EFS)

Defined as the date of randomization to the date of first documented confirmed relapse /progression /death, whichever occurs first

Time frame: Through the end of the study (approximately 4 years)

Overall Survival (OS)

Defined as the time from randomization to the date of death due to any cause. Participants who are alive at the analysis cutoff date will be censored at the date they were last known to be alive.

Time frame: Through the end of the study (approximately 4 years)

Duration of CR and PR

Among participants who achieved CR+PR per IWG 2006 criteria

Time frame: Through the end of the study (approximately 4 years)

Time to CR and PR

Defined as time from the date of the randomization to the date of CR+PR, among participants who achieve CR+PR based on IWG 2006 Response Criteria

Time frame: Through the end of the study (approximately 4 years)

Acute myeloid leukemia (AML) transformation rate

Time frame: Through the end of the study (approximately 4 years)

Time to transfusion independence (TTTI)

Defined as time from date of randomization to date transfusion independence (TI) is first observed (Day 1 of a ≥ 56 days period without a transfusion), among participants who are baseline transfusion dependent and have achieved post-baseline TI. In the event a participant had more than one ≥ 56-day period, which met TI criteria, the earliest period will be used in analysis.

Time frame: Through the end of the study (approximately 4 years)

Duration of transfusion independence (DOTI)

Among participants who have achieved post-baseline TI, DOTI will be calculated as the time from the date TI is first observed (Day 1 of a ≥ 56-day period without a transfusion) until the day before the participants had a subsequent transfusion.

Time frame: Through the end of the study (approximately 4 years)

Transfusion independence rate

Time frame: Through the end of the study (approximately 4 years)

Change from baseline in Quality of life (QOL) based on the QUALMS score

Quality of Life in Myelodysplasia Scale (QUALMS) scores range from 0 to 100, with a higher score representing a better QOL.

Time frame: Through the Event Free Survival Follow up (approximately 4 years)

Change from baseline in health economic outcomes measures based on EQ-5D-5L score

Health economic outcomes measures as assessed by the 5-level EuroQol five dimensions questionnaire (EQ-5D-5L) scores range from 5 to 25 with a higher number representing a worse health status.

Time frame: Through the Event Free Survival Follow up (approximately 4 years)

Number of participants who proceed to hematopoietic stem cell transplantation (HSCT)

Time frame: Through the end of the study (approximately 4 years)

Ivosidenib plasma concentrations

For participants receiving ivosidenib monotherapy

Time frame: Through Cycle 22 (each cycle is 28 days)

2-HG plasma concentrations

For participants receiving ivosidenib monotherapy

Time frame: Through Cycle 22 (each cycle is 28 days)

Number of participants achieving CR and PR by 6 months as per IWG 2006 criteria

Time frame: Through 6 months after starting treatment

Number of participants achieving CR and PR by 6 months as per IWG 2023 criteria

Time frame: Through 6 months after starting treatment

Number of participants achieving CR and PR by 4 months as per IWG 2023 criteria

Time frame: Through 4 months after starting treatment

Number of adverse events (AEs) and serious adverse events (SAEs)

Time frame: Through the Safety Follow-up Visit (30-35 days after discontinuation of treatment)