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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

Important Safety Information Prescribing Information Medication Guide Indications Patient Site Connect with a BLINCYTO® rep

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External Page

NOW AVAILABLEBLINCYTO® offers 72- and 96-hour* infusion durations—offering more flexibility for you and your patients

The choice between these infusion duration options should be made by the treating healthcare professional, considering the frequency of the infusion bag changes and the weight of the patient.†

*Prepared with Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% 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 (eg, ethanol, propylene glycol) which compete with benzyl alcohol for the same metabolic pathway. Serious adverse reactions, including fatal reactions and the “gasping syndrome,” have been reported in very low birth weight neonates born weighing less than 1500 g, and early preterm neonates who received intravenous drugs containing benzyl alcohol as a preservative.

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

Reference: BLINCYTO® (blinatumomab) prescribing information, Amgen.

BLINCYTO® (blinatumomab) logo

R/R: COG AALL1331 study

Study design: A randomized, controlled, open-label, phase 3 study of patients 1–27 years of age with Ph(–) B-cell precursor ALL in first relapse.1

  • Patients in high-risk (HR)* or intermediate-risk (IR)† first relapse: Following one UKALLR3 reinduction chemotherapy block, patients were randomized to receive cycles 1 and 2 of BLINCYTO® (n=105) as post-reinduction consolidation therapy or blocks 2 and 3 of consolidation chemotherapy (n=103) based on the UKALLR3 trial.‡ The primary endpoint was DFS: 54% at 2 years for patients receiving BLINCYTO® vs 39% for patients receiving chemotherapy; P = 0.03; HR: 0.70 (95% CI: 0.47-1.03). The difference was not statistically significant.1
  • Patients in low-risk (LR)§ first relapse: Following one UKALLR3 reinduction chemotherapy block, patients were randomized to receive 3 cycles of BLINCYTO® alternating with chemotherapy (n=127) or chemotherapy alone (n=128), modified from the UKALLR3 regimen. The primary endpoint was DFS : 61.2% at 4 years for patients receiving chemotherapy alternating with BLINCYTO® vs 49.5% for patients receiving chemotherapy alone; P = 0.089; HR: 0.76 (95% CI: 0.51–1.14). The difference was not statistically significant.2
  • Dosing of BLINCYTO® was 15 mcg/m2/day for 28 days, then 7 days off. Premedication with 5 mg/m2/dose of dexamethasone was administered before the first cycle of BLINCYTO®2,3

*Patients who had an iBM or combined BM + EM relapse < 36 months after diagnosis or who had an iEM relapse < 18 months after diagnosis were assigned to the high-risk group.1

†Patients who had an iBM or combined BM + EM relapse ≥ 36 months after diagnosis or who had an iEM relapse ≥ 18 months after diagnosis and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.1

‡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.3,4

§Low risk was defined as iBM or combined BM + EM relapse ≥ 36 months or iEM relapse ≥ 18 months and MRD < 0.1% at end of induction.1

ALL, acute lymphoblastic leukemia; BM, bone marrow; CI, confidence interval; COG, Children's Oncology Group; 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; Ph(–), Philadelphia chromosome–negative; R/R, relapsed or refractory.

BLINCYTO® efficacy was established based on DFS and OS vs chemotherapy in pediatric and AYA patients with B-cell precursor ALL in first relapse1,2

IR* and HR† relapse

2-year DFS for BLINCYTO® vs chemotherapy1

54% BLINCYTO®
(n=105)

vs

39% chemotherapy
(n=103)

(HR: 0.70 [95% CI: 0.47–1.03]; P = 0.03)‡‡The difference was not statistically significant.1

OS for BLINCYTO® vs chemotherapy1

Modal
2-year OS for BLINCYTO® (blinatumomab) vs chemotherapy
  • Median follow-up was 2.9 years1

*Patients who had an iBM or combined BM + EM relapse < 36 months or who had an iEM relapse < 18 months after diagnosis were assigned to the high-risk group.1

†Patients who had an iBM or combined BM + EM relapse ≥ 36 months or who had an iEM relapse ≥ 18 months after diagnosis and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.1

LR§ relapse

  • 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 significant2
  • Median follow-up was 3.5 years2

§Low risk was defined as iBM or combined BM + EM relapse ≥ 36 months or iEM relapse ≥ 18 months and MRD < 0.1% at end of induction.1

AYA, adolescent and young adult; OS, overall survival.

COG AALL1331 study design and baseline characteristics of patients

Patients 1–27 years of age with Ph(–) B-cell precursor ALL in first relapse1-5

Ped_COG_Schematic

Endpoints for HR/IR analysis:1

  • Primary endpoint: Disease-free survival
  • Secondary endpoint: Overall survival
  • Exploratory endpoint: MRD response
  • Post hoc endpoint: Ability to proceed to HSCT

Endpoints for LR analysis:1,2

  • Primary endpoint: Disease-free survival
  • Secondary endpoint: Overall survival
Key inclusion criteria1
B-cell precursor ALL in first relapse
Key exclusion criteria1
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 Committee1

BLINCYTO® was evaluated in pediatric and AYA patients in first relapse1

Baseline characteristics of patients in HR or IR first relapse1

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.
Hypodiploid, 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.1

†Patients who had an iBM or combined BM + EM relapse ≥ 36 months after diagnosis or who had an iEM relapse ≥ 18 months after diagnosis and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.1

‡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.3,4

§Low risk was defined as iBM or combined BM + EM relapse ≥ 36 months or iEM relapse ≥ 18 months and MRD < 0.1% at end of induction.1

Ph(+), Philadelphia chromosome–positive.

  • HR* and IR† groups
    HR_IR_studySchematic

    BLINCYTO® consolidation (n=105)

    • Two cycles of BLINCYTO® (15 mcg/m2/day for 28 days, then 7 days off)
    • Premedication with 5 mg/m2/day of dexamethasone before first cycle of BLINCYTO®

    Chemotherapy consolidation (n=103)

    • Two 4-week blocks of consolidation chemotherapy based on the UKALLR3 trial‡
  • LR group§
    LR_studySchematic

    BLINCYTO® + chemotherapy consolidation (n=127)

    • Dosing of BLINCYTO® was 15 mcg/m2/day for 28 days, then 7 days off. Premedication with 5 mg/m2/dose of dexamethasone was administered before the first cycle of BLINCYTO®
    • Following chemotherapy block 2, BLINCYTO® therapy was alternated with continuation chemotherapy, modified from the UKALLR3 regimen

    Chemotherapy consolidation (n=128)

    • Two chemotherapy blocks, followed by two continuation chemotherapy cycles, modified from the UKALLR3 regimen

Endpoints for HR/IR analysis:1

  • Primary endpoint: Disease-free survival
  • Secondary endpoint: Overall survival
  • Exploratory endpoint: MRD response
  • Post hoc endpoint: Ability to proceed to HSCT

Endpoints for LR analysis:1,2

  • Primary endpoint: Disease-free survival
  • Secondary endpoint: Overall survival
Key inclusion criteria1
B-cell precursor ALL in first relapse
Key exclusion criteria1
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 Committee1

BLINCYTO® was evaluated in pediatric and AYA patients in first relapse1

Baseline characteristics of patients in HR or IR first relapse1

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.
Hypodiploid, 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.1

†Patients who had an iBM or combined BM + EM relapse ≥ 36 months after diagnosis or who had an iEM relapse ≥ 18 months after diagnosis and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.1

‡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.3,4

§Low risk was defined as iBM or combined BM + EM relapse ≥ 36 months or iEM relapse ≥ 18 months and MRD < 0.1% at end of induction.1

Ph(+), Philadelphia chromosome–positive.

The National Comprehensive Cancer Network® (NCCN®) for Pediatric ALL recommends blinatumomab as a treatment option in pediatric and AYA patients with relapsed or refractory B-cell precursor ALL6,7

NCCN Recommended

Safety in first relapse consistent with established safety profile1

Incidence of AEs for patients in HR or IR first relapse receiving BLINCYTO® vs chemotherapy1

BLINCYTO®
Cycle 1 (n=102) 		Chemotherapy Block 2 (n=97) BLINCYTO®
Cycle 2 (n=88) 		Chemotherapy Block 3 (n=62)
Adverse event Any Grade
n (%) 		Grades ≥ 3*
n (%) 		Any Grade
n (%) 		Grades ≥ 3*
n (%) 		Any Grade n (%) Grades ≥ 3* n (%) Any Grade n (%) Grades ≥ 3* n (%)
Patients with any adverse event 99 (97) 77 (76) 89 (92) 88 (91) 81 (92) 49 (56) 55 (89) 52 (84)
Anemia 77 (76) 15 (15) 63 (65) 51 (53) 39 (44) 4 (5) 36 (58) 35 (57)
White blood cell decreased 67 (66) 25 (25) 59 (61) 55 (57) 50 (57) 13 (15) 30 (48) 30 (48)
Alanine aminotransferase increased 65 (64) 12 (12) 62 (64) 38 (39) 37 (42) 6 (7) 27 (44) 8 (13)
Fever 54 (53) 6 (6) 24 (25) 5 (5) 20 (23) 2 (2) 20 (32) 6 (10)
Neutrophil count decreased 51 (50) 34 (33) 58 (60) 57 (59) 43 (49) 25 (28) 32 (52) 31 (50)
Aspartate aminotransferase increased 49 (48) 9 (9) 51 (53) 14 (14) 26 (30) 1 (1) 24 (39) 3 (5)
Hypoalbuminemia 47 (46) 0 43 (44) 6 (6) 18 (21) 0 23 (37) 1 (2)
Lymphocyte count decreased 43 (42) 37 (36) 32 (33) 30 (31) 33 (38) 18 (21) 16 (26) 15 (24)
Platelet count decreased 43 (42) 8 (8) 63 (65) 56 (58) 18 (21) 3 (3) 37 (60) 34 (55)
Hyperglycemia 32 (31) 2 (2) 24 (25) 6 (6) 31 (35) 2 (2) 19 (31) 8 (13)
Hypocalcemia 31 (30) 2 (2) 36 (37) 6 (6) 12 (14) 0 18 (29) 0
Hypokalemia 28 (28) 7 (7) 36 (37) 19 (20) 21 (24) 2 (2) 28 (45) 14 (23)
Hypophosphatemia 18 (18) 0 18 (19) 5 (5) 8 (9) 0 7 (11) 2 (3)
Hypotension 16 (16) 1 (1) 11 (11) 7 (7) 12 (14) 3 (3) 7 (11) 4 (7)
Blood bilirubin increased 15 (15) 2 (2) 31 (32) 7 (7) 4 (5) 0 16 (26) 2 (3)
Infection† 15 (15) 10 (10) 48 (49) 39 (40) 20 (23) 9 (10) 42 (68) 38 (61)
Vomiting 14 (14) 0 20 (21) 2 (2) 15 (17) 1 (1) 13 (21) 4 (7)
GGT increased 12 (12) 4 (4) 9 (9) 5 (5) 5 (6) 1 (1) 3 (5) 1 (2)
Anorexia 11 (11) 4 (5) 15 (16) 12 (12) 6 (7) 2 (2) 8 (13) 4 (7)
Febrile neutropenia 6 (6) 5 (5) 43 (44) 43 (44) 0 0 28 (45) 28 (45)
Mucositis oral 4 (4) 0 44 (45) 25 (26) 2 (2) 1 (1) 16 (26) 5 (8)
Sepsis 1 (1) 1 (1) 13 (13) 13 (13) 2 (2) 2 (2) 14 (23) 14 (23)
Typhlitis 0 0 1 (1) 1 (1) 0 0 4 (7) 4 (7)
BLINCYTO® Cycle 1 (n=102) Chemotherapy Block 2 (n=97)
Adverse event Any Grade
n (%) 		Grades ≥ 3*
n (%) 		Any Grade
n (%) 		Grades ≥ 3*
n (%)
Patients with any adverse event 99 (97) 77 (76) 89 (92) 88 (91)
Anemia 77 (76) 15 (15) 63 (65) 51 (53)
White blood cell decreased 67 (66) 25 (25) 59 (61) 55 (57)
Alanine aminotransferase increased 65 (64) 12 (12) 62 (64) 38 (39)
Fever 54 (53) 6 (6) 24 (25) 5 (5)
Neutrophil count decreased 51 (50) 34 (33) 58 (60) 57 (59)
Aspartate aminotransferase increased 49 (48) 9 (9) 51 (53) 14 (14)
Hypoalbuminemia 47 (46) 0 43 (44) 6 (6)
Lymphocyte count decreased 43 (42) 37 (36) 32 (33) 30 (31)
Platelet count decreased 43 (42) 8 (8) 63 (65) 56 (58)
Hyperglycemia 32 (31) 2 (2) 24 (25) 6 (6)
Hypocalcemia 31 (30) 2 (2) 36 (37) 6 (6)
Hypokalemia 28 (28) 7 (7) 36 (37) 19 (20)
Hypophosphatemia 18 (18) 0 18 (19) 5 (5)
Hypotension 16 (16) 1 (1) 11 (11) 7 (7)
Blood bilirubin increased 15 (15) 2 (2) 31 (32) 7 (7)
Infection† 15 (15) 10 (10) 48 (49) 39 (40)
Vomiting 14 (14) 0 20 (21) 2 (2)
GGT increased 12 (12) 4 (4) 9 (9) 5 (5)
Anorexia 11 (11) 4 (5) 15 (16) 12 (12)
Febrile neutropenia 6 (6) 5 (5) 43 (44) 43 (44)
Mucositis oral 4 (4) 0 44 (45) 25 (26)
Sepsis 1 (1) 1 (1) 13 (13) 13 (13)
Typhlitis 0 0 1 (1) 1 (1)
BLINCYTO® Cycle 2 (n=88) Chemotherapy Block 3 (n=62)
Adverse event Any Grade
n (%) 		Grades ≥ 3*
n (%) 		Any Grade
n (%) 		Grades ≥ 3*
n (%)
Patients with any adverse event 81 (92) 49 (56) 55 (89) 52 (84)
Anemia 39 (44) 4 (5) 36 (58) 35 (57)
White blood cell decreased 50 (57) 13 (15) 30 (48) 30 (48)
Alanine aminotransferase increased 37 (42) 6 (7) 27 (44) 8 (13)
Fever 20 (23) 2 (2) 20 (32) 6 (10)
Neutrophil count decreased 43 (49) 25 (28) 32 (52) 31 (50)
Aspartate aminotransferase increased 26 (30) 1 (1) 24 (39) 3 (5)
Hypoalbuminemia 18 (21) 0 23 (37) 1 (2)
Lymphocyte count decreased 33 (38) 18 (21) 16 (26) 15 (24)
Platelet count decreased 18 (21) 3 (3) 37 (60) 34 (55)
Hyperglycemia 31 (35) 2 (2) 19 (31) 8 (13)
Hypocalcemia 12 (14) 0 18 (29) 0
Hypokalemia 21 (24) 2 (2) 28 (45) 14 (23)
Hypophosphatemia 8 (9) 0 7 (11) 2 (3)
Hypotension 12 (14) 3 (3) 7 (11) 4 (7)
Blood bilirubin increased 4 (5) 0 16 (26) 2 (3)
Infection† 20 (23) 9 (10) 42 (68) 38 (61)
Vomiting 15 (17) 1 (1) 13 (21) 4 (7)
GGT increased 5 (6) 1 (1) 3 (5) 1 (2)
Anorexia 6 (7) 2 (2) 8 (13) 4 (7)
Febrile neutropenia 0 0 28 (45) 28 (45)
Mucositis oral 2 (2) 1 (1) 16 (26) 5 (8)
Sepsis 2 (2) 2 (2) 14 (23) 14 (23)
Typhlitis 0 0 4 (7) 4 (7)
  • The most common (≥ 20%) AEs of any grade among patients in LR first relapse receiving BLINCYTO® cycles 1, 2, or 3 in the BLINCYTO® + chemotherapy arm were anemia, WBC decreased, neutrophil count decreased, fever, lymphocyte count decreased, platelet count decreased, alanine aminotransferase increased, aspartate aminotransferase increased, hypokalemia, infection, and encephalopathy2

*Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grading ranges from 1 to 5, with 3 indicating severe or medically significant but not immediately life-threatening; 4, life-threatening and indicating urgent intervention; and 5, death. Grades were assigned by the treating physician and select serious adverse events, as defined in the protocol, are reported per federal guidelines.1

†Includes catheter-related, lung, skin, upper respiratory tract, and urinary tract infections.1

Select AEs for patients receiving BLINCYTO®1

BLINCYTO®
Cycle 1 (n=102) 		BLINCYTO®
Cycle 2 (n=88)
Adverse event Any Grade
n (%) 		Grades ≥ 3
n (%) 		Any Grade
n (%) 		Grades ≥ 3
n (%)
CRS 22 (22) 1 (1) 1 (1) 0
Encephalopathy 11 (11) 2 (2) 7 (8) 2 (2)
Seizure 4 (4) 1 (1) 1 (1) 0
  • Incidence of most AEs decreased from cycle 1 to cycle 2 of BLINCYTO®1
  • The majority of AEs were mild to moderate in severity1,‡
  • All AEs related to BLINCYTO® were fully reversible, and there were no deaths related to AEs1
  • There were 5 toxic deaths during blocks 2 and 3 of the chemotherapy arm (all infections) and none in the BLINCYTO® arm. Four of the five toxic deaths were AYA patients1

‡Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, in which Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, and Grade 4 is life-threatening.1,8

AE, adverse event; CRS, cytokine release syndrome; GGT, gamma-glutamyl transferase; WBC, white blood cell.

See more

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 of 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 may have a higher risk of seizures with BLINCYTO® therapy; consider seizure prophylaxis prior to initiation of BLINCYTO® for these patients.

    Monitor patients for signs and symptoms of neurological toxicities, including ICANS, and interrupt or discontinue BLINCYTO® and/or treat with corticosteroids 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® 72-Hour bag (with preservative) and 96-Hour bag (with preservative) contain 2.5 mg of benzyl alcohol per mL, and the 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.

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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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References: 1. 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. 2. 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. 3. 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(suppl 2):833-842. 4. 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. 5. 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(suppl):833-842. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Acute Lymphoblastic Leukemia V.3.2025. ©National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed April 21, 2025. 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. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia V.3.2024. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed April 21, 2025. 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. 8. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed April 21, 2025.