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Indications

BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older with:

Philadelphia chromosome-negative disease in the consolidation phase of multiphase chemotherapy ... Read More 

Minimal residual disease (MRD) greater than or equal to 0.1% in first or second complete remission

Relapsed or refractory disease

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NOW APPROVED
for use in frontline consolidation in patients with CD19-positive
Ph(–) B-cell precursor ALL, regardless of MRD status* or age1

BLINCYTO® is indicated in adult and pediatric patients one month and older.1

*In the E1910 study, MRD was assessed centrally using standardized 6-color flow cytometry, with MRD(–) defined as < 0.01% leukemic cells in the bone marrow.2 The MRD tests were performed at laboratory sites using assays that have not been analytically validated by FDA.

ALL, acute lymphoblastic leukemia; CD, cluster of differentiation; FDA, Food and Drug Administration; MRD, measurable or minimal residual disease; Ph(–), Philadelphia chromosome–negative.

Please see Indications in above "Indications" tray and full Important Safety Information,
including BOXED WARNINGS below.

References: 1. BLINCYTO® (blinatumomab) prescribing information, Amgen. 2. Litzow MR, Sun Z, Paietta E, et al. ECOG-ACRIN-E1910 NCTN clinical trial: A phase III randomized trial of blinatumomab for newly diagnosed BCR-ABL-negative B lineage acute lymphoblastic leukemia in adults. Presented at: 64th ASH Annual Meeting and Exposition; December 10–13, 2022; New Orleans, LA.

Choose BLINCYTO® as a treatment option for pediatric and AYA patients with CD19-positive MRD(+) or R/R B-cell precursor ALL1

MT103-205, the pivotal study of BLINCYTO® in pediatric patients with R/R B-cell precursor ALL: International, open-label, single-arm, phase 1/2 study of single-agent BLINCYTO® in 70 patients < 18 years of age with B-cell precursor ALL and > 25% BM blasts who were primary refractory, in first relapse after full salvage induction, in second or later relapse, or in any relapse after HSCT. Primary endpoint was CR/CRh* in first 2 cycles: 33% (n=23/70); (95% CI: 22.1-45.1).1,2,†

Learn more about the MT103-205 pivotal study

CR was defined as ≤ 5% of blasts in the BM, no evidence of circulating blasts or extramedullary disease, and full recovery of peripheral blood counts (platelets > 100,000/μL and ANC > 1,000/μL). CRh* was defined as ≤ 5% of blasts in the BM, no evidence of circulating blasts or extramedullary disease, and partial recovery of peripheral blood counts (platelets > 50,000/μL and ANC > 500/μL).1

Study design: A randomized, controlled, open-label, phase 3 study of BLINCYTO® vs SOC chemotherapy as post-reinduction consolidation therapy prior to HSCT in 111 pediatric patients between 28 days and 18 years of age with Ph(–) B-cell precursor ALL in high-risk first relapse.* After receiving reinduction chemotherapy followed by 2 blocks of high-risk consolidation chemotherapy, patients were randomized to receive one cycle of BLINCYTO® (n=54) or a third block of high-risk SOC consolidation chemotherapy (n=57). Primary endpoint was EFS: Estimated 58% at 5 years§ for patients on BLINCYTO® vs 28%§ for patients receiving SOC chemotherapy; P < 0.001; HR: 0.35 (95% CI: 0.20–0.61). Selected secondary endpoints: OS, incidence of relapse, MRD response, and incidence of AEs.1,3

*High risk was defined as very early or early iBM relapse, very early combined BM + EM relapse, or very early iEM relapse. Very early relapse was defined as < 18 months after primary diagnosis, and early relapse was defined as ≥ 18 months after primary diagnosis and < 6 months after completion of primary therapy.4

Induction therapy and cycles of HC1 and HC2 chemotherapy administered according to the IntReALL HR 2010, ALL-REZ BFM 2002, ALL R3, COOPRALL, and AIEOP ALL REC 2003 protocols.3

Third block of consolidation chemotherapy, HC3, included: dexamethasone IV/vincristine IV/daunorubicin IV/methotrexate IV/ifosfamide IV/PEG-asparaginase IV/IM.5

§Months were calculated as days from randomization date to event/censor date, divided by 30.5.1

BLINCYTO® demonstrated superior EFS and OS vs SOC chemotherapy in pediatric patients with B-cell precursor ALL in high-risk first relapse1

EFS for BLINCYTO® vs SOC chemotherapy1

 

EFS for BLINCYTO® (blinatumomab) vs chemotherapy

EFS for BLINCYTO® (blinatumomab) vs chemotherapy

*

Based on KM estimates. Months were calculated as days from randomization date to event/censor date, divided by 30.5.1

Stratification factors were: age (1 to 9 years vs other [< 1 year and > 9 years]) and marrow/MRD status (M1 with MRD level < 10-3 vs M1 with MRD level ≥ 10-3 vs M2).1

The hazard ratio estimates were obtained from the Cox proportional hazard model. A hazard ratio < 1.0 indicates a lower average event rate and a longer EFS for BLINCYTO® relative to SOC chemotherapy.1

  • The overall median follow-up time for EFS was 51.9 months1
  • For Study 20120215, MRD was assessed by real-time quantitative PCR and multicolor flow cytometry. Assessment of minimal residual disease by PCR and flow cytometry was conducted in parallel, unless material was limited, in which case PCR, the most sensitive and robust investigator-independent method, was used. PCR is considered the criterion standard for quantifying minimal residual disease and has been validated by the study groups managing pediatric and adult patients with ALL. The analytical validity of the MRD assay by flow cytometry cannot be confirmed3

5-year KM estimates for OS for BLINCYTO® vs SOC chemotherapy1,§

5-year OS estimates for BLINCYTO® (blinatumomab) vs SOC chemotherapy

5-year OS estimates for BLINCYTO® (blinatumomab) vs SOC chemotherapy

  • At the median follow-up of 55.2 months, median OS was not reached in the BLINCYTO® arm and was 25.6 months in the SOC chemotherapy arm [HR: 0.33 [95% CI: 0.16–0.66];**,†† P = 0.001‡‡)1
§

Months were calculated as days from randomization date to event/censor date, divided by 30.5.1

**

Stratification factors were: age (1 to 9 years vs other [< 1 year and> 9 years]) and marrow/MRD status (M1 with MRD level < 10-3 vs M1 with MRD level ≥ 10-3 vs M2). 1

††

The hazard ratio estimates were obtained from the Cox proportional hazard model. A hazard ratio < 1.0 indicates a lower average event rate and a longer survival for BLINCYTO® relative to SOC chemotherapy.1

‡‡

The P-value was derived using the stratified log-rank test.1

AE, adverse event; ALL, acute lymphoblastic leukemia; ANC, absolute neutrophil count; AYA, adolescent and young adult; BM, bone marrow; CD, cluster of differentiation; CI, confidence interval; CR, complete remission; CRh*, complete remission with partial hematologic recovery; EFS, event-free survival; EM, extramedullary; HC1, high-risk consolidation block 1; HC2, high-risk consolidation block 2; HC3, high-risk consolidation block 3; HR, hazard ratio; HSCT, allogeneic hematopoietic stem cell transplantation; iBM, isolated bone marrow; iEM, isolated extramedullary; IM, intramuscular; IV, intravenous; KM, Kaplan-Meier; MRD, measurable or minimal residual disease; OS, overall survival; PCR, polymerase chain reaction; Ph(–), Philadelphia chromosome-negative; R/R, relapsed or refractory; SOC, standard-of-care.

Most patients who received BLINCYTO® achieved MRD negativity vs SOC chemotherapy1

MRD
response rate

94%

(n=46/49)

of patients who received BLINCYTO® achieved MRD negativity* vs 53% (n=26/49) of patients who received SOC chemotherapy1

*

Included patients for which evaluable baseline MRD marker could be found with PCR. MRD response was analyzed at end of treatment with investigational product (cycle 1 day 29). Patients who were missing MRD assessment at the end of treatment were considered to not have a response.1

Amgen 20120215 study design and baseline characteristics of patients

Patients > 28 days and < 18 years of age with Ph(–) B-cell precursor ALL in high-risk first relapse1,3,*

Reinduction chemotherapy followed by 2 blocks of high-risk consolidation chemotherapy
 
1:1
Randomization
 
1
 
 
1
 
 
 
BLINCYTO® consolidation (n=54)
One cycle of BLINCYTO® (15 mcg/m2/day for 28 days)
 
SOC chemotherapy consolidation (n=57)
Third block of high-risk consolidation SOC chemotherapy
 
 
 
 
 
HSCT
Reinduction chemotherapy followed by 2 blocks of high-risk consolidation chemotherapy
 
1:1
Randomization
 
1
 
 
1
 
 
 
BLINCYTO®
consolidation (n=54)
One cycle of BLINCYTO® (15 mcg/m2/day for 28 days)
 
SOC chemotherapy consolidation (n=57)
Third block of high-risk consolidation SOC chemotherapy
 
 
 
 
 
HSCT

Primary endpoint:1

  • Event-free survival

Selected secondary endpoints:3

  • Overall survival
  • Incidence of relapse
  • MRD response
  • Incidence of AEs
Key inclusion criteria3
High-risk B-cell precursor ALL in first relapse
< 5% blasts or between 5%< 25% blasts in BM
Key exclusion criteria5
Clinically relevant CNS pathology requiring treatment
Evidence of current CNS (CNS2, CNS3) involvement by ALL§
Abnormal renal or hepatic function prior to start of treatment
Enrollment was closed early based on the statistically significant difference in efficacy of BLINCYTO® vs chemotherapy at a predefined efficacy threshold of approximately 50% EFS events interim analysis3

*High risk was defined as very early or early iBM relapse, very early combined BM + EM relapse, or very early iEM relapse. Very early relapse was defined as < 18 months after primary diagnosis, and early relapse was defined as ≥ 18 months after primary diagnosis and < 6 months after completion of primary therapy.4

Induction therapy and cycles of HC1 and HC2 chemotherapy, administered according to the IntReALL HR 2010, ALL-REZ BFM 2002, ALL R3, COOPRALL, and AIEOP ALL REC 2003 protocols.3

Third block of consolidation chemotherapy, HC3, included: dexamethasone IV/vincristine IV/daunorubicin IV/methotrexate IV/ifosfamide IV/PEG-asparaginase IV/IM.5

§CNS2, patients with WBC count in CSF < 5 per μL and having blasts in the CSF; CNS3, patients with WBC count in CSF ≥ 5 per μL and having blasts in the CSF.6

CNS, central nervous system; CSF, cerebrospinal fluid; WBC, white blood cell.

See the full safety profile of the Amgen 20120215 study

Learn more

Study design: A randomized, controlled, open-label, phase 3 study of 208 patients 1–27 years of age with Ph(–) B-cell precursor ALL in high-risk* or intermediate-risk first relapse of B-cell precursor ALL.†,‡ Following one UKALLR3 reinduction chemotherapy block, patients in the high-risk and intermediate-risk groups were randomized to receive cycles 1 and 2 of BLINCYTO® (n=105) as post-reinduction consolidation therapy or blocks 2 and 3 of chemotherapy consolidation (n=103) based on the UKALLR3 trial.§ The primary endpoint was DFS: 54% at 2 years for patients receiving BLINCYTO® (n=105) vs 39% for patients receiving chemotherapy (n=103); P = 0.03; HR: 0.70 (95% CI: 0.47–1.03). Secondary endpoint: OS, exploratory endpoint: MRD response, post hoc endpoint: ability to proceed to HSCT.7

*

Patients who had an iBM or combined BM + EM relapse < 36 months or who had an iEM relapse < 18 months were assigned to the high-risk group.7

Patients who had an iBM or combined BM + EM relapse ≥ 36 months or who had an iEM relapse ≥ 18 months and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.7

A low-risk randomization arm was also part of the study.7

§

UKALLR3: induction, IT methotrexate/dexamethasone oral/mitoxantrone IV or idarubicin IV/vincristine IV/pegaspargase IM; consolidation, dexamethasone oral/vincristine IV/IT methotrexate/methotrexate IV/pegaspargase IM/cyclophosphamide IV/etoposide IV; maintenance, IT methotrexate/dexamethasone oral/vincristine IV/cytarabine IV/Erwinase IM/methotrexate IV; before HSCT, fludarabine IV/cytarabine IV/liposomal daunorubicin citrate IV.7,8

ALL, acute lymphoblastic leukemia; BM, bone marrow; CI, confidence interval; DFS, disease-free survival; EM, extramedullary; HR, hazard ratio; HSCT, allogeneic hematopoietic stem cell transplantation; iBM, isolated bone marrow; iEM, isolated extramedullary; IM, intramuscular; IT, intrathecal; IV, intravenous; MRD, measurable or minimal residual disease; OS, overall survival; Ph(–), Philadelphia chromosome–negative; R/R, relapsed or refractory.

BLINCYTO® demonstrated improved DFS and OS vs chemotherapy for high-risk and intermediate-risk pediatric and AYA patients7,*,†

2-year DFS for BLINCYTO® vs chemotherapy7

OS for BLINCYTO® vs chemotherapy7

OS for BLINCYTO® vs chemotherapy

OS for BLINCYTO® vs chemotherapy

  • Median follow-up was 2.9 years7
  • The COG AALL1331 study also contained a low-risk (LR) group. In the LR group, 127 eligible patients were randomized to receive chemotherapy plus BLINCYTO® and 128 eligible patients were randomized to receive chemotherapy alone. The median follow-up was 3.5 years. The 4-year DFS rate was 61.2% ± 5.0% in the BLINCYTO® arm and 49.5% ± 5.2% in the chemotherapy arm (HR: 0.76; 95% CI: 0.51–1.14; P = 0.089). The difference was not statistically significant9

*Patients who had an iBM or combined BM + EM relapse < 36 months or who had an iEM relapse < 18 months were assigned to the high-risk group.7

Patients who had an iBM or combined BM + EM relapse ≥ 36 months or who had an iEM relapse ≥ 18 months and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.7

AYA, adolescent and young adult; COG, Children's Oncology Group.

More patients achieved an MRD response and proceeded to HSCT with BLINCYTO® vs chemotherapy7

MRD response after cycle 1 of BLINCYTO® vs block 2 of chemotherapy7,*

MRD
response rate

75%

(n=79/105)

of patients who received BLINCYTO® achieved MRD negativity vs 32% (n=33/103) of patients who received chemotherapy

  • MRD response was an exploratory endpoint. Analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn7

More patients who received BLINCYTO® proceeded to HSCT vs those who received chemotherapy7

Proceeded t HSCT

Proceeded t HSCT

  • Number of patients who proceeded to HSCT while in remission was part of a post hoc analysis. Analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn7

*All patients received one block of chemotherapy prior to randomization. Data reflect MRD response for patients who received the first cycle of BLINCYTO® in the BLINCYTO® treatment arm vs patients who received the second block of chemotherapy in the chemotherapy treatment arm.7

MRD < 0.01%, evaluated in a central laboratory by flow cytometry.7

In this analysis, positive MRD or no MRD data are considered as not having negative MRD. The rationale for including patients with no MRD data is that the lack of MRD data was due to death, relapse, or removal from protocol therapy because of an AE or other poor response to therapy, so it is appropriate to include them as the converse of the optimal outcome of being able to submit a sample and have negative MRD.7

AE, adverse event.


COG AALL1331 study design and baseline characteristics of patients

Patients 1–27 years of age with Ph(–) B-cell precursor ALL in high-risk or intermediate-risk first relapse7

BLINCYTO® (blinatumomab) consolidation

BLINCYTO® (blinatumomab) consolidation

Primary endpoint:7

Disease-free survival

Secondary endpoint:7

Overall survival

Exploratory endpoint:7

MRD response

Exploratory endpoint:7

MRD response

Secondary endpoint:7

Overall survival

Post hoc endpoint:7

Ability to proceed to HSCT

Key inclusion criteria7
B-cell precursor ALL in first relapse


Key exclusion criteria7
Down syndrome
Ph(+) B-cell precursor ALL
Previous HSCT or BLINCYTO® treatment
Enrollment was terminated early in the HR and IR groups due to encouraging efficacy and lower rates of serious toxicity in the BLINCYTO® arm vs chemotherapy, based on a recommendation from the Independent Data Safety Monitoring Committee7

BLINCYTO® was evaluated in high-risk and intermediate-risk pediatric and AYA patients in first relapse7

Baseline characteristics7


BLINCYTO ®
(n=105)
n (%)
Chemotherapy
(n=103)
n (%)
Age at enrollment (years)
Median (interquartile range)
9 (6–16) 9 (5–16)
1–9 55 (52.4) 55 (53.4)
10–12 10 (9.5) 11 (10.7)
13–17 25 (23.8) 19 (18.4)
18–20 8 (7.6) 10 (9.7)
21–27 7 (6.7) 8 (7.8)
Sex
Female 48 (45.7) 49 (47.6)
Male 57 (54.3) 54 (52.4)
Risk group assignment after reinduction
High risk* 69 (65.7) 69 (67.0)
Intermediate risk 36 (34.3) 34 (33.0)
Cytogenetic group at diagnosis
Favorable
ETV6-RUNX1, No.
Hyperdiploid with +4, +10, No.
21 (23.3)
12
9
16 (17.6)
8
8
Unfavorable
KMT2A-rearranged, No.
Hyperdiploid, No.
7 (7.8)
7
0
10 (11.0)
9
1
Other
Unknown, No.
62 (68.9)
15
65 (71.4)
12
 

*Patients who had an iBM or combined BM + EM relapse < 36 months or who had an iEM relapse < 18 months were assigned to the high-risk group.7

Patients who had an iBM or combined BM + EM relapse ≥ 36 months or who had an iEM relapse ≥ 18 months and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.7

A low-risk randomization arm was also part of the study.7

§UKALLR3: induction, IT methotrexate/dexamethasone oral/mitoxantrone IV or idarubicin IV/vincristine IV/pegaspargase IM; consolidation, dexamethasone oral/vincristine IV/IT methotrexate/methotrexate IV/pegaspargase IM/cyclophosphamide IV/etoposide IV; maintenance, IT methotrexate/dexamethasone oral/vincristine IV/cytarabine IV/Erwinase IM/methotrexate IV; before HSCT, fludarabine IV/cytarabine IV/liposomal daunorubicin citrate IV.7,8

HR, high risk; IR, intermediate risk; Ph(+), Philadelphia chromosome–positive.



See the safety results of BLINCYTO® vs chemotherapy in COG AALL1331

Learn more

Study design: International, open-label, single-arm, phase 1/2 study of single-agent BLINCYTO® in patients < 18 years of age with > 25% BM blasts who were primary refractory, in first relapse after full salvage induction, in second or later relapse, or in any relapse after HSCT. Primary endpoint was CR/CRh* in first 2 cycles: 33% (n=23/70); (95% CI: 22.1–45.1).1,2

About a third of all patients achieved CR/CRh* within the first 2 cycles of BLINCYTO®1

Primary endpoint was CR/CRh* in the first 2 cycles1,†

Within the First Two Treatment Cycles of BLINCYTO®

Within the first two treatments of BLINCYTO® (blinatumomab) 33% of patients
achieved CR/CRh Within the first two treatments of BLINCYTO® (blinatumomab) 33% of patients
achieved CR/CRh
  • 73.9% of CR/CRh* occurred in cycle 1 (n=17/23)1
  • 26.1% of CR/CRh* occurred in cycle 2 (n=6/23)1

MT103-205 study design and baseline characteristics of patients

  • MT103-205 study design: an international, open-label, single-arm, phase 1/2 study1

BLINCYTO® was studied as a single-agent therapy via continuous IV infusion2

  • Phase 1: Dose finding
  • Phase 2:
    • Dosage: 5/15 mcg/m2/day (5 mcg/m2/day for the first week of the first cycle followed by 15 mcg/m2/day thereafter)
    • Treatment cycle: 4 weeks on treatment, 2 weeks off
Key inclusion criteria2
Primary refractory disease
First relapse after full salvage induction
Second or later relapse, or in any relapse after HSCT
Age < 18 years
KPS ≥ 50% or LPS ≥ 50% for patients < 16 years of age

Key exclusion criteria2
Active acute or extensive chronic GvHD after HSCT
Evidence of active CNS involvement
Evidence of active testicular involvement
MT103-205 included heavily pretreated pediatric patients2

Baseline Characteristics (N=70)2,*

Sex, n (%)
Male 47 (67)
Age, n (%)
< 2 years 10 (14)
2–6 years 20 (29)
7–17 years 40 (57)
Previous relapses, n (%)
0 (primary refractory disease) 2 (3)
1 31 (44)
2 29 (41)
≥ 3 8 (11)
Previous HSCT, n (%) 40 (57)
Baseline BM blasts, n (%)
< 50% 18 (26)
≥ 50% 52 (74)

MRD(+): Retrospective study

BLAST, the pivotal study of BLINCYTO® in adult patients with MRD(+) B-cell precursor ALL: N=86, an open-label, single-arm phase 2 study of adult patients with MRD(+) B-cell precursor ALL who had received at least 3 chemotherapy blocks of standard ALL therapy, were in hematologic complete remission (defined as < 5% blasts in bone marrow, absolute neutrophil count > 1 Gi/L, platelets > 100 Gi/L), and had MRD* at a level of ≥ 0.1% using an assay with a minimum sensitivity of 0.01%. Primary endpoint: 81% (n=70/86) of patients had no detectable MRD assessed after 1 treatment cycle with BLINCYTO®.1,10,*

In a retrospective study (Keating, et al), nearly all pediatric patients on BLINCYTO® achieved MRD negativity and subsequently proceeded to allogeneic hematopoietic stem cell transplantation (HSCT).11

A multi-institutional, retrospective study to report outcomes using BLINCYTO® as therapy prior to HSCT11

  • Pediatric patients (N=15) aged 0–21 years with MRD(+) B-cell precursor ALL11,†
  • All patients were in CR at enrollment11
    • Two-thirds of the patients (10/15) were in CR1 and one-third (5/15) were in CR2
  • More than half of patients (9/15) had unfavorable risk cytogenetic abnormalities11
  • 93% (n=14/15) of patients had no detectable MRD following BLINCYTO® therapy11
  • Median time from end of BLINCYTO® treatment to preparative regimen for HSCT was 14 days (range: 1–35 days)11
    • All patients had successful neutrophil engraftment with a median time of 19 days (range: 11–35 days)
  • There are ongoing trials investigating BLINCYTO® in MRD(+) patients12

*Defined as the absence of detectable MRD confirmed in an assay with minimum sensitivity of 0.01% for 6 patients and ≤ 0.005% for 80 patients. Undetectable MRD was achieved by 65 of 80 patients with an assay sensitivity of at least 0.005%.1

Most patients (n=12) received a single 4-week course of BLINCYTO® at 15 mcg/m2/day; 2 patients had their initial cycle of BLINCYTO® shortened to start HSCT preparative therapy (at days 18 and 20), and 1 patient received 2 courses for a total of 66 days.11

Defined as < 5% blasts in the bone marrow.11

ALL, acute lymphoblastic leukemia; CR1, first complete remission; CR2, second complete remission; MRD, measurable or minimal residual disease.

MRD(+) and R/R: The NCCN Guidelines for Pediatric ALL recommend blinatumomab as a treatment option for pediatric patients with B-cell precursor ALL in first relapse and those who test MRD(+)§ in first or second complete remission13

§

The threshold for MRD positivity may vary based on the protocol being followed and/or the assay being used.13

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

  • Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® and treat with corticosteroids as recommended.
  • Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS), which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
Contraindications

BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions
  • Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. The median time to onset of CRS is 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin, and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO® overlap with those of infusion reactions, capillary leak syndrome (CLS), and hemophagocytic histiocytosis/macrophage activation syndrome (MAS). Using all these terms to define CRS in clinical trials of BLINCYTO®, CRS was reported in 15% of patients with R/R ALL, in 7% of patients with MRD-positive ALL, and in 16% of patients receiving BLINCYTO® cycles in the consolidation phase of therapy. If severe CRS occurs, interrupt BLINCYTO® until CRS resolves. Discontinue BLINCYTO® permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS.
  • Neurological Toxicities, including Immune Effector Cell-Associated Neurotoxicity Syndrome: BLINCYTO® can cause serious or life-threatening neurologic toxicity, including ICANS. The incidence of neurologic toxicities in clinical trials was approximately 65%. The median time to the first event was within the first 2 weeks of BLINCYTO® treatment. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Grade 3 or higher neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. The majority of neurologic toxicities resolved following interruption of BLINCYTO®, but some resulted in treatment discontinuation.

    The incidence of signs and symptoms consistent with ICANS in clinical trials was 7.5%. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. There is limited experience with BLINCYTO® in patients with active ALL in the central nervous system (CNS) or a history of neurologic events. Patients with a history or presence of clinically relevant CNS pathology were excluded from clinical studies. Patients with Down Syndrome over the age of 10 years may have a higher risk of seizures with BLINCYTO® therapy.

    Monitor patients for signs and symptoms of neurological toxicities, including ICANS, and interrupt or discontinue BLINCYTO® as outlined in the PI. Advise outpatients to contact their healthcare professional if they develop signs or symptoms of neurological toxicities.

  • Infections: Approximately 25% of patients receiving BLINCYTO® in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO® as needed.
  • Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO® treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO® as needed to manage these events.
  • Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO® infusion and interrupt BLINCYTO® if prolonged neutropenia occurs.
  • Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures and ICANS, patients receiving BLINCYTO® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO® is being administered.
  • Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO® treatment with a median time to onset of 3 days. In patients receiving BLINCYTO®, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase, and total blood bilirubin prior to the start of and during BLINCYTO® treatment. BLINCYTO® treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if total bilirubin rises to > 3 times ULN.
  • Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO® in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO® and dexamethasone as needed.
  • Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO®, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
  • Preparation and administration errors have occurred with BLINCYTO® treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
  • Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO® treatment, during treatment, and until immune recovery following last cycle of BLINCYTO®.
  • Benzyl Alcohol Toxicity in Neonates: Serious adverse reactions, including fatal reactions and the “gasping syndrome,” have been reported in very low birth weight (VLBW) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) who received intravenous drugs containing benzyl alcohol as a preservative. Early preterm VLBW neonates may be more likely to develop these reactions, because they may be less able to metabolize benzyl alcohol.

    Use the preservative-free preparations of BLINCYTO® where possible in neonates. When prescribing BLINCYTO® (with preservative) for neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO® (with preservative), other products containing benzyl alcohol or other excipients (e.g., ethanol, propylene glycol) which compete with benzyl alcohol for the same metabolic pathway.

    Monitor neonatal patients receiving BLINCYTO® (with preservative) for new or worsening metabolic acidosis. The minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known. The BLINCYTO® 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL.

  • Embryo-Fetal Toxicity: Based on its mechanism of action, BLINCYTO® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with BLINCYTO® and for 48 hours after the last dose.
Adverse Reactions
  • The safety of BLINCYTO® in adult and pediatric patients one month and older with MRD-positive B-cell precursor ALL (n=137), relapsed or refractory B-cell precursor ALL (n=267), and Philadelphia chromosome-negative B-cell precursor ALL in consolidation (n=165) was evaluated in clinical studies. The most common adverse reactions (≥ 20%) to BLINCYTO® in this pooled population were pyrexia, infusion-related reactions, headache, infection, musculoskeletal pain, neutropenia, nausea, anemia, thrombocytopenia, and diarrhea.
Dosage and Administration Guidelines
  • BLINCYTO® is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
  • It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
INDICATIONS

BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older with:

  • Philadelphia chromosome-negative disease in the consolidation phase of multiphase chemotherapy
  • Minimal residual disease (MRD) greater than or equal to 0.1% in first or second complete remission
  • Relapsed or refractory disease

Please see BLINCYTO® full Prescribing Information, including BOXED WARNINGS.

BLINCYTO® is a registered trademark of Amgen Inc.

References: 1. BLINCYTO® (blinatumomab) prescribing information, Amgen. 2. von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016;34:4381-4389. 3. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325:843-854. 4. Data on file, Amgen; 2020. 5. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(suppl):843-854. 6. Brown PA, Ji L, Xu X, et al. Effect of post-reinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia. JAMA. 2021;325(suppl 2):833-842. 7. Brown PA, Ji L, Xu X, et al. Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325:833-842. 8. Parker C, Waters R, Leighton C, et al. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomized trial. Lancet. 2010;376:2009-2017. 9. Hogan LE, Brown PA, Ji L, et al. Children's Oncology Group AALL1331: Phase III trial of blinatumomab in children, adolescents, and young adults with low-risk B-cell ALL in first relapse. J Clin Oncol. 2023. doi:10.1200/JCO.22.02200. 10. Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131:1522-1531. 11. Keating AK, Gossai N, Phillips CL, et al. Reducing minimal residual disease with blinatumomab prior to HCT for pediatric patients with acute lymphoblastic leukemia. Blood Adv. 2019;3:1926-1929. 12. ClinicalTrials.gov. https://classic.clinicaltrials.gov/ct2/results?term=blinatumomab&cond=Residual+Disease%2C+Minimal&recrs=b&recrs=a&recrs=f&recrs=d&age_v=&gndr=&type=Intr&rslt=&Search=Apply. Accessed January 2, 2024. 13. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Acute Lymphoblastic Leukemia V.3.2024. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed February 8, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

  • Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® and treat with corticosteroids as recommended.
  • Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS), which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
Contraindications
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