Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Partial response is defined as regression (<50% decrease in size of masses) of measureable disease and no new sites.

The time from documentation of the first assessment of either partial or complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.

The time from documentation of the first assessment of complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.

The time from documentation of the first assessment of partial response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.

The time from the date of first blinatumomab infusion until the date of diagnosis of progression of lymphoma, the start date of new anti-tumor treatment (excluding any stem cell transplantation) or date of death, whichever is the earliest. Patients alive who did not have progression or new anti-tumor treatment (excluding any stem cell transplantation) were censored at last date of tumor assessment.

The time from the date of first blinatumomab infusion until death as a result of any cause. Patients still alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. For patients who withdrew their informed consent, only information until the date of withdrawal was analyzed.

Adverse events were evaluated for severity according to the grading scale provided in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

An adverse event or suspected adverse drug reaction was considered "serious" if it resulted in one of the following outcomes:

• Resulted in death;
• Was life-threatening;
• Required inpatient hospitalization or prolongation of existing hospitalization;
• Resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions;
• Was a congenital anomaly or birth defect;
• Was a medically important condition.

The Investigator used medical judgment to determine whether there was a causal relationship (ie, related [reasonably possible] or unrelated [not reasonably possible]) between an adverse event and blinatumomab.

Blinatumomab serum levels were analyzed using a validated cluster of differentiation (CD)69 activation bioassay with a lower limit of quantification (LLOQ) of 50 pg/mL. Steady-state concentration (Css) was based on actual dose received, rather than based on cohort or time or day.

Leukocyte (white blood cells) counts were analyzed by differential blood count analysis.

Lymphocyte counts were analyzed by differential blood count analysis.

CD19+ B-cell counts were analyzed by flow cytometry.

CD19+ B-cell counts were analyzed by flow cytometry.

CD3+ T-cell counts were analyzed by flow cytometry.

CD3+ T-cell counts were analyzed by flow cytometry.

CD4+ T-cell counts were analyzed by flow cytometry.

CD4+ T-cell counts were analyzed by flow cytometry.

CD8+ T-cell counts were analyzed by flow cytometry.

CD8+ T-cell counts were analyzed by flow cytometry.

CD19+ B-cells and CD3+ T-cell counts were analyzed by flow cytometry.

CD4+ T-cells and CD8+ T-cell counts were analyzed by flow cytometry.

CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.

CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.

Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.

Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.

Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.

Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.

CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.

CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.

Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.

Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.

Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.

Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.

Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.

Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.

Participants received blinatumomab administered CIV at a constant dose of 112 µg/day for 8 weeks of treatment during Cycle 1. Participants who achieved a CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Participants received blinatumomab administered CIV 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. Participants who achieved CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Total of all reporting groups

Participants received blinatumomab CIV at a constant dose of 112 µg/day for 8 weeks of treatment during Cycle 1. Participants who achieved a CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Participants received blinatumomab administered CIV 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. Participants who achieved CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Complete response is defined as the disappearance of all evidence of disease.

Efficacy set

Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Partial response is defined as regression (<50% decrease in size of masses) of measureable disease and no new sites.

Efficacy set

The time from documentation of the first assessment of either partial or complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.

Efficacy set with an overall objective response of CR or PR during the first treatment cycle

The time from documentation of the first assessment of complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.

Efficacy set with a best overall response of CR during the first treatment cycle

The time from documentation of the first assessment of partial response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.

Efficacy set with a best overall response of PR during the first treatment cycle

The time from the date of first blinatumomab infusion until the date of diagnosis of progression of lymphoma, the start date of new anti-tumor treatment (excluding any stem cell transplantation) or date of death, whichever is the earliest. Patients alive who did not have progression or new anti-tumor treatment (excluding any stem cell transplantation) were censored at last date of tumor assessment.

Efficacy set

The time from the date of first blinatumomab infusion until death as a result of any cause. Patients still alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. For patients who withdrew their informed consent, only information until the date of withdrawal was analyzed.

Efficacy set

Adverse events were evaluated for severity according to the grading scale provided in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

An adverse event or suspected adverse drug reaction was considered "serious" if it resulted in one of the following outcomes:

• Resulted in death;
• Was life-threatening;
• Required inpatient hospitalization or prolongation of existing hospitalization;
• Resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions;
• Was a congenital anomaly or birth defect;
• Was a medically important condition.

The Investigator used medical judgment to determine whether there was a causal relationship (ie, related [reasonably possible] or unrelated [not reasonably possible]) between an adverse event and blinatumomab.

Safety analysis set

Blinatumomab serum levels were analyzed using a validated cluster of differentiation (CD)69 activation bioassay with a lower limit of quantification (LLOQ) of 50 pg/mL. Steady-state concentration (Css) was based on actual dose received, rather than based on cohort or time or day.

Pharmacokinetic (PK) data set (all participants who received any infusion of blinatumomab and had at least one PK sample collected).

Leukocyte (white blood cells) counts were analyzed by differential blood count analysis.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Lymphocyte counts were analyzed by differential blood count analysis.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD19+ B-cell counts were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD19+ B-cell counts were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD3+ T-cell counts were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD3+ T-cell counts were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD4+ T-cell counts were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD4+ T-cell counts were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD8+ T-cell counts were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD8+ T-cell counts were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD19+ B-cells and CD3+ T-cell counts were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD4+ T-cells and CD8+ T-cell counts were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Participants received blinatumomab administered CIV at a constant dose of 112 µg/day for 8 weeks of treatment during Cycle 1. Participants who achieved CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Participants received blinatumomab administered CIV 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. Participants who achieved CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Participants received blinatumomab administered CIV 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. Participants who achieved CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

All participants who received blinatumomab by continuous intravenous infusion during the core study.