Selinexor (KPT-330) in Older Patients With Relapsed AML

Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact.

Time frame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

Population: Intent-to-treat (ITT) population included all participants who were randomized to study treatment under PV\>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV\>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV\>=5).

EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.

Time frame: Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)

Population: PP Population included all participants randomized to study treatment under PV \>=5.0 who received any amount of study treatment and who had no major protocol violations that compromised assessment of efficacy. Here, N= number of participants evaluable for this measure and n =Participants evaluable for this outcome measure at specified categories

QoL was assessed by the FACT-Leu. FACT-Leu combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific sub-scale (17 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI; total of 31 items) was the primary measurement of interest, comprising the Physical and Functional sub-scales plus the leukemia - specific sub-scale. Each item was rated on a 5-point Likert scale. Range from 0 = (Not at all) to 4 = (Very much); therefore, the TOI had a score ranging from 0 to 124. Higher scores indicated improvement in well being. The QoL assessment was performed at baseline (prior to first dose of study treatment), Day 1 of each cycle on or after the second, and at the final visit.

Time frame: Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)

Population: Per-Protocol (PP) population: all participants randomized to study treatment under PV\>=5.0 who received any amount of study treatment and had no major protocol violations that compromised assessment of efficacy. Here, N= number of participants evaluable for this measure and n=participants evaluable for this outcome measure at specified categories.

Duration of DCR calculated for all participants with DCR. CR: \< 5% myeloblasts in BM, absence of circulating blasts, hematologic recovery (peripheral blood ANC \>1000 cells/microL and platelet count \> 100,000/microL, no need for RBC transfusions), absence of extra medullary disease. PR: No circulating blasts, Neutrophil count \>=1.0 x 10\^9/L, Platelet count \>= 100 x 10\^9/L, \>= 50 % reduction in BM blast to 6% to 25%, or blasts \<= 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (\<1 x 10\^9/L) or thrombocytopenia (\<100 x 10\^9/L), CRi; \< 5% BM blasts with residual neutropenia \[ANC \< 1000 cells/microL\] or thrombocytopenia \[platelets \< 100,000/microL\]. MLFS; morphologic BM blast clearance to \< 5% in a marrow sample in which \<=200 cells enumerated/cellularity is \>= 10%, in absence of blasts with Auer rods, no hematologic recovery required and SD; failure to achieve a response but not meeting criteria for disease progression over period of \> 4 weeks.

Time frame: Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria

Population: ITT population included all participants who were randomized to study treatment under PV\>=5.0, regardless of whether or not they received study treatment. Here, N signifies number of participants evaluable for this measure.

DOR was calculated from date of response of CR, CRi, CRp, MLFS, or PR to date of progression or recurrence based on IWG criteria. CR: \<5% myeloblasts in bone marrow,absence of circulating blasts, hematologic recovery (peripheral blood ANC \>1000 cells/microL, platelet count \> 100,000/microL, no need for RBC transfusions), absence of extramedullary disease. PR: No circulating blasts, neutrophil count \> =1.0 x10\^9/L, platelet count \>= 100 x10\^9/L, \>= 50 % reduction in bone marrow blast to 6% to 25%, or blasts less than or equal to (\<=) 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (\<1x10\^9/L) or thrombocytopenia (\<100 x10\^9/L), CRi; \< 5% bone marrow blasts with residual neutropenia \[ANC \< 1000 cells/microL\] or thrombocytopenia \[platelets \< 100,000/microL\]. MLFS: morphologic bone marrow blast clearance to \< 5% in marrow sample, \<= 200 cells enumerated/cellularity is ≥ 10%, in absence of blasts with Auer rods, no hematologic recovery required.

Time frame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

Population: ITT population included all participants who were randomized to study treatment under PV\>=5.0, regardless of whether or not they received study treatment. Here, N signifies number of participants evaluable for this outcome measure.

DFS for CRR based on IWG criteria, was calculated from the first date of response of CR to the date of progression or recurrence, or date of death if progression or recurrence did not occur. Participants who discontinued prior to disease progression or recurrence or did not progress as of the time of the analysis were censored at the time of last radiologic assessment. CR per IWG 2003 criteria was defined as morphologic presence of \< 5 % myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC \> 1000 cells/microL and platelet count \> 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease.

Time frame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

Population: ITT population:all participants who randomized to study treatment under PV\>=5.0, regardless of whether or not they received study treatment. This outcome measure(OM) was only defined for CR participants. For Physician Choice 2,there was zero CR participants.Overall Number of Participants Analyzed (N): Number of participants evaluable for this OM.

DFS based on IWG criteria was defined as the duration from start of the complete response achieved until disease progression or death from any cause. Responses defined by IWG 2003 Response Criteria: Morphologic CR: \< 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC \> 1000 cells/microL and platelet count \> 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (\<1x10\^9/L) or thrombocytopenia (\<100 x10\^9/L), Cri (\< 5% bone marrow blasts with residual neutropenia \[ANC \< 1000 cells/microL\] or thrombocytopenia \[platelets \< 100,000/microL\]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.

Time frame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

Population: ITT population included all participants who were randomized to study treatment under PV \>=5.0, regardless of whether or not they received study treatment. Here, N signifies number of participants evaluable for this outcome measure.

CRR was analyzed using International Working Group (IWG) 2003 criteria, as the difference in the proportions of participants with IWG results of CR. CR per IWG 2003 criteria was defined as morphologic presence of \< 5 percentage (%) myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood absolute neutrophil count (ANC) \> 1000 cells/microliter (microL) and platelet count \> 100,000/microL, with no need for red blood cell (RBC) transfusions), and the absence of extramedullary disease.

Time frame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

Population: ITT population included all participants who were randomized to study treatment under PV\>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV\>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV\>=5).

DCR:Point estimate of % of participants with CR,CRi,CRp,MLFS,PR, or SD for \<=4 weeks.CR:\<5% myeloblasts in bone marrow (BM),absence of circulating blasts,hematologic recovery(peripheral blood ANC \>1000 cells/microL and platelet count \>100,000/microL, no need of RBC transfusions),absence of extramedullary disease. PR:No circulating blasts,Neutrophil count \>=1.0 x10\^9/L, Platelet count \>= 100\*10\^9/L, \>=50% reduction in BM blast to 6% to 25%, or blasts \<=5% if Auer rods are present.CRp:All criteria for CR except for residual neutropenia (\<1\*10\^9/L) or thrombocytopenia(\<100 x10\^9/L),CRi;\< 5% BM blasts with residual neutropenia \[ANC \< 1000 cells/microL\] or thrombocytopenia \[platelets \< 100,000/microL\]. MLFS:morphologic BM blast clearance to \<5% in a marrow sample in which \<=200 cells enumerated or cellularity is ≥10%,in absence of blasts with Auer rods,no hematologic recovery required,SD:failure to achieve a response but not meeting criteria for disease progression over period of \>4 weeks.

Time frame: Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria

Population: ITT Population included all participants who were randomized to study treatment under PV\>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV\>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV\>=5).

mCRR was defined as the point estimate of the percentage of participants who had CR, CRi, or CRp. Responses defined as per IWG 2003 response criteria: Morphologic CR:\< 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC \> 1000 cells/microL and platelet count \> 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (\<1x10\^9/L) or thrombocytopenia (\<100 x10\^9/L), Cri (\< 5% bone marrow blasts with residual neutropenia \[ANC \< 1000 cells/microL\] or thrombocytopenia \[platelets \< 100,000/microL\]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.

Time frame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

Population: ITT population included all participants who were randomized to study treatment under PV\>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV\>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV\>=5).

Overall response rate was defined as the point estimate of the percentage of participants who achieved CR (disappearance of all target and non-target lesions), partial response (PR) (\>=30 % decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions). CRi; \< 5% BM blasts with residual neutropenia \[ANC \< 1000 cells/microL\] or thrombocytopenia \[platelets \< 100,000/microL\]. CRp; All criteria for CR except for residual neutropenia (\<1x10\^9/L) or thrombocytopenia (\<100 x10\^9/L) and morphologic leukemia-free state (MLFS); morphologic BM blast clearance to \<5% in a marrow sample in which \<=200 cells enumerated or cellularity is ≥10%, in absence of blasts with Auer rods, no hematologic recovery required.

Time frame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

Population: ITT population included all participants who were randomized to study treatment under PV\>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV\>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV\>=5).

Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.

Time frame: From randomization (Day 1) up to 3 months

Population: ITT population included all participants who were randomized to study treatment under PV \>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV\>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV\>=5).