Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)

OS is defined as the number of months measured from the date of randomization to the date of death from any cause. Kaplan Meier (KM) estimates were used for analysis.

Time frame: From randomization up to 32.62 months

Population: Participants from intent-to-treat analysis set were analyzed.

The percentage of participants (CR rate) are participants who reach morphologic CR (morphological blast of ≤ 5% and recovery of absolute neutrophil count (ANC), platelets, and hemoglobin from complete blood counts as well as peripheral blast) based on Investigator-assessed International Working Group (IWG) myelodysplastic syndrome (MDS) criteria on or prior to initiation of any new anticancer therapy, including stem cell therapy (SCT). Percentages were rounded off.

Time frame: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

DOCR=Time from first CR date to the first date of relapse, disease progression (PD) or death, prior to initiation of any new anticancer therapy excluding SCT whichever occurs earlier. PD is defined as: \<5% blasts: ≥50 increase in blasts to \>5% blasts,5%-10% blasts: ≥50% increase in blasts to \>10% blasts, 10%-20% blasts: ≥50% increase in blasts to \>20% blasts,20%-30% blasts: ≥50% increase in blasts to \>30% blasts, any of the following: at least 50% decrement from maximum remission/response in granulocytes or platelets. Reduction in Hgb by ≥2 g/dL / Transfusion dependence. Relapse is defined as return to pretreatment bone marrow blast percentage / decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets/ reduction in Hgb concentration by ≥ 1.5 g/dL or transfusion dependence. CR is defined in outcome measure 1. KM estimates were used for analysis.

Time frame: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set who achieved CR were analyzed.

DOR is measured from time measurement criteria are first met for objective response to first date of relapse, disease progression (PD) /death, prior to initiation of any new anticancer therapy excluding SCT whichever occurs earlier. Disease progression and relapse have been defined in outcome measure number 3. KM estimates were used for analysis.

Time frame: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set with objective response were analyzed.

EFS is defined as the time from randomization to transformation to acute myeloid leukemia (AML) or death from any cause, whichever occurs first. Transformation assessments and deaths post SCT were included in the analysis. KM estimates were used for analysis

Time frame: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

The FACT-Anemia response rate is defined as the percentage of participants who showed clinically meaningful improvement in health-related quality of life (HRQoL) based on the score from the FACT-Anemia instrument prior to initiation of any new anticancer therapy, including SCT. The minimal clinically meaningful difference of 7.0 was used as cutoff for clinically meaningful improvement. The FACT-Anemia instrument consists of 5 subscales, including physical well-being, emotional well-being, functional well-being, social well-being, and anemia symptoms. Each subscale measures items on a 5-point Likert scale from 0 to 4, where 0 = not at all and 4 = very much. The subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest quality of life (QOL) and 100 denotes the highest QOL. Percentages were rounded off.

Time frame: Up to week 136

Population: Participants from intent-to-treat analysis set were analyzed.

The MRD-negative response rate is defined as the percentage of participants who achieved a morphologic CR or marrow CR based on Investigator-assessed IWG criteria and reached MRD-negative disease status prior to initiation of any new anticancer therapy, including SCT. MRD-negative disease status was assessed using a multiparameter flow cytometry-based assay performed by a central laboratory. Morphologic CR and marrow CR are defined in outcome measures 1 and 4, respectively. Percentages were rounded off.

Time frame: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

ORR is defined as the percentage of participants who reach objective response including CR, partial remission (PR), marrow CR or hematological improvement prior to initiation of any new anticancer therapy including SCT for MDS per IWG 2006 criteria per investigator's evaluation. CR is defined in outcome measure 1. PR is defined as all CR criteria if abnormal before treatment except, one marrow blasts decreased by ≥ 50% over pretreatment but still \> 5% cellularity and morphology not relevant. Marrow CR is defined as bone marrow ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment, stable disease with any hematological improvement, peripheral blood: if hematological improvement responses, they were noted in addition to marrow CR. Stable Disease: Failure to achieve at least PR, but no evidence of progression for \> 8 weeks. Percentages were rounded off.

Time frame: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

TEAE's are defined as any AEs with an onset date on or after the study drug start date, no later than 70 days after study drug last dose date or day before initiation of new anticancer therapy including SCT. If AE onset date is on or before last dose date, it is considered as TEAE regardless of start of new anticancer therapy. An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product or other protocol imposed intervention, regardless of attribution. An event is considered serious, if it results death, life-threatening, inpatient or prolongation hospitalization, incapacity or substantial disruption of the ability to conduct normal functions, a congenital anomaly/birth defect, and important medical events.

Time frame: First dose date up to 135.9 weeks plus 70 days (Up to 2.8 years)

Population: Participants from safety analysis set with data available were analyzed. The safety analysis set included all randomized participants who took at least 1 dose of any study treatment, with treatment assignment designated according to the actual treatment received.

CR in TP53 mutant population is defined as the percentage of participants who achieve a morphologic CR based on investigator assessments using IWG criteria on or prior to initiation of any new anticancer therapy, including SCT in TP53 mutant population. Percentages were rounded off.

Time frame: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set with TP53 mutation were analyzed.

Percentages were rounded off.

Time frame: Up to 72 hours before administration of any treatment at Day 1, Cycle 1; within 24 hours prior to any study drug administration at Day 1 of Cycles 2, 3, 5, 7, 10, and 13 and End of Treatment (± 7 Days after last study drug dose); Cycle length is 28 Days

Population: Participants in Immunogenicity Analysis Set with at least 1 baseline anti-drug antibody (ADA) sample and at least post-treatment ADA Sample were analyzed. Immunogenicity Analysis Set includes participants who took at least 1 dose of magrolimab and have at least 1 reported ADA result.

PFS is defined as the time from randomization to the date of documented DP (including treatment failure by IWG criteria or relapse after PR/CR), or death from any cause, whichever occurs first. Response assessments and deaths post SCT were included in the analysis. Treatment failure is defined as, Death during treatment or disease progression characterized by worsening cytopenia, increase in percentage of bone marrow blasts, or progression to a more advanced MDS FAB subtype than pretreatment. Relapse after CR or PR = Return to pretreatment bone marrow blast percentage / Decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets / Reduction in Hgb concentration by ≥ 1.5 g/dL or transfusion dependence. CR, PR and PD are defined in outcome measures 1, 4 and 5 respectively. KM estimates were used for analysis.

Time frame: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

RBC transfusion independence rate is defined as the percentage of participants who have a 56-day or longer period with no RBC transfusions at any time between randomization and initiation of any new anticancer therapy, including SCT, among all participants who were RBC transfusion-dependent at Baseline. Percentages were rounded off.

Time frame: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set who were RBC transfusion-dependent at baseline were analyzed.

Pretreatment assessments for the initial dose may be collected up to 72 hours before administration of study treatment; thereafter, pretreatment assessments are to be collected within 24 hours prior to study treatment administration.

Time frame: Preinfusion on Days 0, 7, 28, 56, 112, 168, 252 and 336

Population: Pharmacokinetic (PK) analysis set included all participants who took at least 1 dose of magrolimab and had at least 1 measurable post-treatment serum concentration of magrolimab. Participants with data available at the given timepoint were analyzed.

Time to transformation to AML is defined as the time from randomization to the collection date of bone marrow sample leading to documented AML diagnosis. Transformation assessments post SCT were included in the analysis.KM estimates were used for analysis.

Time frame: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.