Blinatumomab in Adults With Relapsed/Refractory Philadelphia Positive B-precursor Acute Lymphoblastic Leukemia

Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts.

Complete remission was defined as meeting all 3 of the following criteria:

• less than or equal to 5% blasts in the bone marrow;
• no evidence of disease
• full recovery of peripheral blood counts: platelets > 100,000/μl, and absolute neutrophil count (ANC) > 1000/μl.

Complete remission with partial hematological recovery (CRh*) was defined as meeting all 3 of the following criteria:

• less than or equal to 5% blasts in the bone marrow
• no evidence of disease
• partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl.

Participants without a post-baseline disease assessment were considered non-responders.

Bone marrow samples were evaluated for MRD remission by a central laboratory using bcr-abl fusion gene reverse transcription polymerase chain reaction (RT-PCR).

An MRD response was defined as MRD < 10^-4 measured by PCR. Participants with no post-baseline MRD assessment were considered non-responders.

Duration of response was measured for participants in remission (CR/CRh*), and was measured from the time the participant first achieved remission until first documented relapse or death from disease progression. Participants without a documented relapse (hematological or extramedullary) and who did not die were censored at the time of the last bone marrow assessment or the last survival follow-up visit to confirm remission. Participants who died without having reported hematological relapse or without showing any clinical sign of disease progression were censored on their date of death.

Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts.

Complete remission was defined as meeting all 3 of the following criteria:

• less than or equal to 5% blasts in the bone marrow;
• no evidence of disease;
• full recovery of peripheral blood counts: platelets > 100,000/μl, and absolute neutrophil count (ANC) > 1000/μl.

Participants without a post-baseline disease assessment were considered non-responders.

Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts.

Complete remission with partial hematological recovery (CRh*) was defined as meeting all 3 of the following criteria:

• less than or equal to 5% blasts in the bone marrow;
• no evidence of disease;
• partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl.

Participants without a post-baseline disease assessment were considered non-responders.

Efficacy was evaluated via a central bone marrow aspiration and local peripheral blood counts.

Complete remission was defined as meeting the following criteria:

• less than or equal to 5% blasts in the bone marrow;
• no evidence of disease;
• full recovery of peripheral blood counts: platelets > 100,000/μl, and absolute neutrophil count (ANC) > 1000/μl.

Complete remission with partial hematological recovery was defined as meeting the following criteria:

• less than or equal to 5% blasts in the bone marrow;
• no evidence of disease;
• partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl.

Complete remission with incomplete hematologic recovery was defined as meeting all of the following criteria:

• less than or equal to 5% blasts in the bone marrow;
• no evidence of disease;
• incomplete recovery of peripheral blood counts: platelets > 100,000/μl or ANC > 1000/μl.

Participants without a post-baseline disease assessment were considered non-responders.

Overall survival was assessed from the date the participant received the first infusion of blinatumomab until death from any cause or the date of the last follow-up.

Participants still alive at the data cut-off date were censored on the last documented visit date or the date of the last contact when the patient was last known to have been alive.

Participants who achieved remission (CR/CRh*) during the first 2 cycles of treatment and received an allogeneic HSCT.

The analysis of 100-day mortality after allogeneic HSCT was assessed for participants who received an allogeneic HSCT while in remission (CR/CRh*) after 2 cycles of blinatumomab treatment and did not receive any additional antileukemic treatment. 100-day mortality after allogeneic HSCT was calculated relative to the date of allogeneic HSCT.

The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants 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.

Adverse events (AEs) were graded for severity according to the CTCAE version 4.0, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living.

Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.

Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Treatment-related adverse events (TRAEs) were those assessed by the investigator as possibly related to blinatumomab based on response to the question: Is there a reasonable possibility that the event may have been caused by blinatumomab or other protocol-specified therapies/procedures?

Anti-blinatumomab binding antibodies were evaluated with a validated blinatumomab anti-drug antibody assay with the electrochemiluminescence detection technology.