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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.

Intervene early with BLINCYTO®

Study design: 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®.* Select secondary endpoints: OS, hematologic RFS at 18 months, duration of hematologic remission.1,2

BLINCYTO® (blinatumomab) is an established approach to achieving MRD negativity early in frontline consolidation1

*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

In the BLAST study, most patients achieved MRD negativity with BLINCYTO®1

Primary endpoint: complete MRD response*

81%

(n=70/86)

of patients had no detectable MRD

  • Complete measurable residual disease (MRD) response was similar across patient subgroups (age, relapse history, and MRD burden)2
Percentage of patients who proceeded to allogeneic hematopoietic stem cell transplantation (HSCT)1
First complete remission

74%

(n=45/61)

Second complete remission

56%

(n=14/25)

At 5 years, a median OS had yet to be reached for patients who achieved MRD negativity3,†

Median OS in patients with vs without a complete MRD response

Median OS in patients with vs without a complete MRD response Median OS in patients with vs without a complete MRD response

Patient response n Median OS 95% CI
MRD responders at cycle 1 84 NR 29.5–NR
MRD nonresponders at cycle 1 23 14.4 months 3.8–32.3

  • Median follow-up for OS was 59.8 months3
  • An OS benefit has not been demonstrated in a randomized, controlled trial
  • Due to the differential effect of HSCT on OS, interpretation of the results of OS cannot exclude potential confounding of HSCT2
  • It is unknown whether achieving MRD negativity alone provides an OS benefit comparable to that of HSCT. Therefore, the survival benefit cannot be isolated to BLINCYTO® treatment alone
  • In the BLAST study, OS was not a primary objective and the study was not powered to assess OS efficacy2
  • Median OS was 36.5 months (95% CI: 22.0–NE) overall following treatment with BLINCYTO® and reached a plateau3
  • Median OS was not estimable (ie, not reached) among the subsets of patients who had achieved a complete MRD response with BLINCYTO® in first complete remission or who proceeded to HSCT in CCR3
See safety data of BLINCYTO® in patients with MRD(+) B-cell precursor ALL

In the BLAST pivotal study, patients†,‡ who achieved MRD negativity had significantly longer RFS2,6

Relapse free survival (RFS)§ in patients with vs without complete MRD response**,††
RFS in patients with vs without complete MRD response

Intervening early in first complete remission with BLINCYTO® resulted in nearly 3x longer RFS vs second complete remission1

Median RFS‡‡ in patients§§ who were MRD(+) treated in first complete remission vs second complete remission

First complete remission(n=61)
 
 

35.2 months

(range: 0.4–53.5 months)

Second complete remission(n=25)
 
 

12.3 months

(range: 0.7–42.3 months)

Use BLINCYTO® early in frontline consolidation to achieve MRD negativity and enable patients to live disease-free longer1

BLAST study design and baseline characteristics of patients

BLAST study design: a single-arm, phase 2 study of BLINCYTO® treatment for adult patients with MRD(+) B-cell precursor ALL1,2,4

N=86

Adults ≥ 18 years of age with B‑cell precursor ALL in hematologic first complete remission or second complete remission with MRD ≥ 0.1%*

BLINCYTO® single-agent immunotherapy

  • Continuous IV infusion for up to 4 cycles
  • Treatment cycle: 4 weeks on therapy, 2 weeks off
  • Dosing: 15 mcg/m2/day (equivalent to 28 mcg/day)
  • Eligible patients could undergo HSCT after 1 cycle

Follow-up:
30 days (safety);
24 months plus
5-year survival follow-up

Primary endpoint:2

  • Complete MRD response after 1 treatment cycle

Select secondary endpoints:2

  • OS
  • Hematologic RFS at 18 months
  • Duration of hematologic remission
Key inclusion criteria1
Adults 18 years of age with B-cell precursor ALL in hematologic complete remission
Measurable residual disease (MRD) level of 0.1% (molecular relapse or molecular failure)§
< 5% blasts in bone marrow
ANC > 1 Gi/L
Platelets > 100 Gi/L
Key exclusion criteria4
Prior HSCT
Presence of circulating blasts or current extramedullary disease
History of relevant CNS pathology or current relevant CNS pathology
Prior systemic cancer chemotherapy within 2 weeks or radiotherapy within 4 weeks

Most patients were in first complete remission at baseline1

Baseline characteristics of patients (N=86)
Age
Median, years (min, max) 43 (18, 76)
≥ 65 years, n (%) 10 (12)
Males, n (%) 50 (58)
Philadelphia chromosome disease status, n (%)
Positive 1 (1)
Negative 85 (99)
Relapse history, n (%)
In first complete remission 61 (71)
In second complete remission 25 (29)
Baseline MRD levels,* n (%)
≥ 10% 7 (8)
≥ 1% and < 10% 34 (40)
≥ 0.1% and < 1% 45 (52)

Blinatumomab (BLINCYTO®) is the only NCCN Guidelines—recommended treatment option in consolidation for adult patients with Ph(–) B-cell precursor ALL who have persistent or rising MRD; the NCCN Guidelines recommend “therapy aimed at eliminating MRD prior to allogeneic HCT,” when possible.7

Study design: A large (N=405), international, randomized, controlled, phase 3 study of single-agent BLINCYTO® vs SOC chemotherapy in patients ≥ 18 years of age: refractory to primary induction therapy or to last therapy, in first relapse (first remission duration < 12 months), in second or later relapse, or in any relapse after HSCT. Primary endpoint was mOS: 7.7 months for BLINCYTO® (n=271) vs 4.0 months for SOC chemotherapy (n=134); P = 0.012; HR: 0.71 (95% Cl: 0.55–0.93).1 Selected secondary endpoints: CR within 12 weeks after initiation of treatment, CR/CRh*/CRi within 12 weeks after initiation of treatment, MRD remission rate, duration of remission, adverse event rates.1,8

BLINCYTO® is an established chemo-minimizing approach that significantly improved survival vs SOC chemotherapy1

BLINCYTO® nearly doubled median overall survival vs SOC chemotherapy1

Primary endpoint: overall survival (intent-to-treat population)1

*A censored subject is indicated by a vertical bar.1

ALL, acute lymphoblastic leukemia; CI, confidence interval; CR, complete remission; DOR, duration of response; HR, hazard ratio; HCT, hematopoietic cell transplantation; HSCT, allogeneic hematopoietic stem cell transplantation; mOS, median overall survival; MRD, measurable or minimal residual disease; NCCN, National Comprehensive Cancer Network; OS, overall survival; Ph(–), Philadelphia chromosome-negative; QoL, quality of life; R/R, relapsed or refractory; SOC, standard-of-care.

Intervening with BLINCYTO® in first salvage more than doubled median OS vs SOC chemotherapy9,*

OS in patients treated in first salvage9,*

*OS in patients treated in first salvage was a prespecified subgroup analysis in TOWER; however, the OS efficacy in this subgroup was not a study objective and the study was not powered to assess OS efficacy in this subgroup.10

A censored subject is indicated by a vertical bar.9

NR, not reached.

BLINCYTO® demonstrated improved overall survival for patients not proceeding to HSCT8,*

Patients not proceeding to HSCT still achieved an OS benefit when treated with BLINCYTO®

*OS in patients censored for allogeneic transplant was a prespecified sensitivity subgroup analysis in TOWER; however, the OS efficacy in this subgroup was not a study objective, and the study was not powered to assess OS efficacy in this subgroup.10

Patients receiving BLINCYTO® achieved higher rates and longer duration of remission vs SOC chemotherapy8,†

CR/CRh*/
CRi rates of

44%

(n=119/271)

(95% CI: 37.9–50.0)

for patients treated with BLINCYTO® vs 25% (n=33/134) (95% CI: 17.6–32.8) for patients treated with SOC chemotherapy8 (P < 0.001)

Median duration of remission for patients who achieved CR/CRh*/CRi8

Median duration of response for patients who achieved CR/Crh/Cri
Median duration of response for patients who achieved CR/Crh/Cri
  • CR/CRh*/CRi rates achieved within 12 weeks after treatment initiation8
  • 53% (n=60/114) of patients in first salvage treated with BLINCYTO® achieved CR/CRh*/CRi8
    • CR/CRh*/CRi in patients treated in first salvage was a prespecified subgroup analysis in TOWER; however, the CR/CRh*/CRi in this subgroup was not a study objective and the study was not powered to assess efficacy in this subgroup

CR was defined as ≤ 5% blasts in the BM, no evidence of disease, and full recovery of peripheral blood counts (platelets > 100,000/microliter and ANC > 1,000/microliter). CRh* was defined as ≤ 5% blasts in the BM, no evidence of disease, and partial recovery of peripheral blood counts (platelets > 50,000/microliter and ANC > 500/microliter). CRi was defined as ≤ 5% blasts in the BM, no evidence of disease, and incomplete recovery of peripheral blood counts (platelets > 100,000/microliter or ANC > 1,000/microliter).8

ANC, absolute neutrophil count; BM, bone marrow; CRh*, complete remission with partial hematologic recovery; CRi, complete remission with incomplete hematologic recovery.

BLINCYTO® helped patients achieve and maintain a durable remission through up to 9 cycles11

27 patients in the landmark phase 3 TOWER study proceeded to continued therapy with BLINCYTO® after induction and consolidation11

74%

(n=20/27)

of patients achieved a best response of complete remission during continued therapy

  • Patients who received BLINCYTO® and had bone marrow blasts ≤ 5% after induction (up to 2 cycles) and consolidation (up to 3 cycles) with BLINCYTO® were eligible to receive continued therapy for an additional 12 months (4 weeks on treatment, 8 weeks off)11
  • At the time of data collection for patients receiving continued therapy, 11 patients were continuing therapy with BLINCYTO®, while 16 had discontinued therapy due to: completion of maintenance therapy (n=3); intention to receive HSCT (n=4); intention to receive treatment other than HSCT (n=2); relapse (n=6); or an AE (n=1)11
  • During continued therapy of cycles 6–9, no new safety concerns were identified; treatment-emergent AEs included:11
    • 4 patients had a neurological event
    • 1 patient had cytokine release syndrome (CRS)
  • Overall, safety event rates were lower in the continued therapy cycles vs the induction or consolidation cycles11

Patients treated with BLINCYTO® had higher MRD negativity rates than patients treated with SOC chemotherapy8

MRD negativity rates for patients who achieved CR/CRh*/CRi with BLINCYTO® vs SOC chemotherapy8

BLINCYTO®

76%

(n=90/119)

vs SOC chemotherapy (n=16/33): 48%

See the safety data from the TOWER study

Molecular remission was assessed in patients achieving CR/CRh*/CRi, and was defined as MRD by PCR or flow cytometry with a minimum assay sensitivity of < 1 x 10–4.8

PCR, polymerase chain reaction.

BLINCYTO® differences in HRQoL measures from baseline vs SOC chemotherapy12

Mean changes in HRQoL functional domains and symptoms at the end of Cycle 1 (Day 29)12

  • These data come from an analysis of a secondary descriptive endpoint from a phase 3 study. The endpoint measured the change from baseline of scores from a validated PRO instrument* during the first cycle of treatment13
  • The study was not powered to assess statistical differences in QoL measures between BLINCYTO® and SOC chemotherapy treatment groups13
  • Select AE rates for patients treated with BLINCYTO® were fatigue (12.7%), back pain (13.1%), nausea (19.1%), vomiting (12.4%), insomnia (10.5%), constipation (12.7%), and diarrhea (21.7%)14

Click here for the EORTC QoL Questionnaire from the TOWER Study15

*The PRO instrument—The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)—is a validated self-rating questionnaire used to assess patients’ perceptions of treatment effectiveness in oncology.13

AE, adverse event; HRQoL, health-related quality of life; PRO, patient-reported outcome.

TOWER study design and baseline characteristics of patients

  • TOWER landmark phase 3 study: BLINCYTO® single-agent immunotherapy was compared with SOC chemotherapy in a large, international, prospective, randomized, controlled, phase 3 trial of 405 patients with Ph(–) R/R B-cell precursor ALL1
2
 
 
1
 
BLINCYTO® single-agent immunotherapy (n=271)1
  • Continuous IV infusion for 1 to 2 induction cycles (4 weeks on, 2 weeks off)8
  • 9 mcg/day on days 1–7 of cycle 1 and 28 mcg/day on subsequent days8
 
SOC chemotherapy (investigator's choice of one of the regimens below) (n=134)1
  • FLAG ± anthracycline-based regimen
  • HiDAC-based regimen
  • High-dose methotrexate-based regimen
  • Clofarabine-based regimen
 
 
Consolidation, maintenance, and follow-up, depending on response to induction8
 
 
2
 
 
1
 
BLINCYTO® single-agent immunotherapy (n=271)1
  • Continuous IV infusion for 1 to 2 induction cycles (4 weeks on, 2 weeks off)8
  • 9 mcg/day on days 1–7 of cycle 1 and 28 mcg/day on subsequent days8
 
SOC
chemotherapy (investigator's choice of one of the regimens below) (n=134)1
  • FLAG ± anthracycline-based regimen
  • HiDAC-based regimen
  • High-dose methotrexate-based regimen
  • Clofarabine-based regimen
 
 
 
Consolidation, maintenance, and follow-up, depending on response to induction8
 
 

Prephase treatment:

  • All patients with > 50% bone marrow blasts received dexamethasone (10 mg/m2/day up to a maximum of 24 mg/day) prior to randomization to reduce the risk of CRS associated with high tumor burden:1
    • 14% (n=37/267) of patients treated with BLINCYTO® experienced CRS of any grade, and 3% (n=8/267) experienced ≥ Grade 316

Premedication:

  • Patients treated with BLINCYTO® were premedicated with 20 mg dexamethasone within 1 hour before infusion1,16

Primary endpoint:8

  • OS

Selected secondary endpoints:8

  • CR within 12 weeks after initiation of treatment
  • CR/CRh*/CRi within 12 weeks after initiation of treatment
  • MRD remission rate
  • Duration of remission
  • Adverse event rates
Key inclusion criteria 1,8
Patients ≥ 18 years of age
Ph(–) R/R B-cell precursor ALL occurring as refractory to primary induction therapy or to last therapy, or untreated first relapse (first remission duration < 12 months), or in second or later relapse, or in any relapse after HSCT
With > 5% blasts in the BM and ECOG PS ≤ 2
Key exclusion criteria 8
Other active cancers
Clinically relevant pathologic condition of the CNS
Isolated extramedullary disease
Autoimmune disease
Acute GvHD of Grade ≥ 2, active chronic GvHD
Allogeneic stem cell transplantation within 12 weeks before randomization
Autologous stem cell transplantation within 6 weeks before randomization
Chemotherapy or radiotherapy within 2 weeks before randomization
Use of immunotherapy within 4 weeks before randomization
Ongoing use of investigational treatment

BLINCYTO® was studied in a wide range of adult patients, including those with a poor prognosis8

Baseline characteristics of the study population1,8

BLINCYTO®
(N=271)
SOC Chemotherapy (N=134)
Age
Mean ± SD, years 41 ± 17 41 ± 17
Range, years 18–80 18–78
Study entry criteria, n (%)
Refractory to primary or salvage therapy 115 (42) 54 (40)
In early first relapse (CR1 duration < 12 months) 76 (28) 37 (28)
In untreated second or later relapse§ 32 (12) 16 (12)
Relapsed after HSCT§ 46 (17) 27 (20)
Not specified 2 (1) 0
Prior salvage therapy, n (%) 171 (63) 70 (52)
Prior transplant, n (%)
Yes 94 (35) 46 (34)
No 176 (65) 87 (65)
Unknown 1 (0) 1 (1)
Disease burden, n (%)
≥ 50% BM blasts 201 (74) 104 (78)
  • Patients in late first relapse (≥ 12 months after initial remission) were excluded8
BLINCYTO® is the only immunotherapy to deliver superior OS and deep, durable remission vs SOC chemotherapy in adult patients with Ph(-) R/R B-cell precursor ALL1,8,10,14,17

Blinatumomab (BLINCYTO®) is an NCCN-recommended Category 1 therapy option for adult patients with Ph(–) R/R B-cell precursor ALL7

In a real-world evidence study, the observed efficacy of BLINCYTO® was reflective of clinical study data1,8,18,*

A majority of patients in a study of real-world evidence were high-risk with unfavorable risk cytogenetic abnormalities18

  • These data are derived from a retrospective, multicenter study of 239 patients across 11 academic centers in the US, of which 190 selected patients were identified as starting with standard BLINCYTO® dosing and no concomitant treatments (eg, TKI, chemotherapy, rituximab, or any combination of these):18
    • Patients who did not receive BLINCYTO® for Ph(–) R/R B-cell ALL consistent with the FDA labeling were excluded in this subset analysis
    • Of the 190 patients included in this subset analysis, 159 had Ph(–) R/R B-cell ALL. The remaining 31 patients had Ph(+) R/R B-cell ALL and are excluded from this data presentation
  • Medical records were reviewed to collect demographic, patient-related, disease-related, and clinical outcome data18
  • Patients were evaluated for OS (from the time of BLINCYTO® initiation), CR, DOR, MRD response, cumulative incidence of HSCT, and adverse events18
    • OS was estimated from the time of BLINCYTO® treatment initiation to death or lost to follow-up
    • CR was defined as ≤ 5% BM blasts, no evidence of disease in the BM, and recovery of peripheral blood count (platelet count > 100,000/µl and ANC > 1,000/µl)
    • DOR was estimated among patients achieving a CR/CRi after BLINCYTO® from time of CR/CRi to progression or death
    • MRD was assessed with the use of multicolor flow cytometry
    • The cumulative incidence of HSCT was estimated using the Nelson-Aalen estimate with death without HSCT as competing risk

*Five patients who could not titrate to the full dose due to tolerance were included in the analysis.18

Ph(–), Philadelphia chromosome–negative; Ph(+), Philadelphia chromosome–positive; TKI, tyrosine kinase inhibitor.

In the real-world evidence study, OS was observed in patients who received BLINCYTO®18,*,†

Median OS18

9.2 months

(n=158)

  • Median follow-up of 18 months18
  • Median OS was 9.1 months among patients with ≥ 50% BM blasts at initiation of BLINCYTO®18

*One patient did not have data available for the survival analysis and is not included in the survival analyses. However, note that this patient is included in the toxicity and response evaluations.18

Estimated from the time of BLINCYTO® treatment initiation to death or lost to follow-up.18

In the real-world evidence study, responses were observed in patients who received BLINCYTO®18,*,†

CR/CRi
rates of

57%

(n=86/151)
for patients on
BLINCYTO®

Median DOR for patients who achieved CR/CRi18,‡

19.6 months

for patients treated with BLINCYTO®

(n=86)

Duration of response by tumor burden18

efficacy-duration-of-response-desktop
efficacy-duration-of-response-mobile

*The exact assessment timing was not specified for this endpoint.18

Data were missing for 8 patients in this analysis.18

Adjusted for HSCT.18

In the real-world evidence study, the majority of patients in CR achieved MRD negativity with BLINCYTO®, and nearly half of all patients proceeded to HSCT18,*

MRD response

78%

(n=65/83) for patients
in CR treated
with BLINCYTO®

Proceeded to HSCT18

45%

for all patients treated with BLINCYTO®

(n=71/159)

  • MRD was assessed using flow cytometry in this analysis vs flow cytometry and PCR in the TOWER study. Additionally, the timing of when MRD and CR was assessed was not specified. In the TOWER study, patients were assessed for these endpoints within 12 weeks of treatment initiation18

*The exact assessment timing was not specified for this endpoint.18

See the safety results of the TOWER landmark study and real-world evidence study

Baseline characteristics of patients in the real-world evidence study

Baseline characteristics (n=159)18

Age*
Mean ± SD, years 45 ± 17
Range, years 8–79
Study entry criteria, n (%)
Refractory to primary therapy 41 (26.6)
< 18 months to first progression 76 (49.4)
Cytogenetic abnormalities, n (%)
No 62 (39.0)
Yes 97 (61.0)
≥ 3 previous therapies, n (%) 36 (22.8)
Prior transplant, n (%)
Yes 27 (17.0)
No 132 (83.0)
BM blasts at initiation of BLINCYTO®, n (%)
BM blasts ≥ 50%, n (%) 57 (45.2)

*Pediatric patients were included in this analysis.

Real-world evidence provides additional data outside of a clinical trial that may support the choice of BLINCYTO® in adults with Ph(–) R/R B-cell precursor ALL18

Study design: BLINCYTO® single-agent immunotherapy was evaluated in an open-label, single-arm, multicenter phase 2 study (N=45) in adult patients with Ph(+) R/R B-cell precursor ALL who progressed after, or were intolerant to second- or later-generation TKI therapy and were intolerant or refractory to imatinib. Primary endpoint was CR/CRh* rate within the first 2 treatment cycles: 36% (n=16/45; 95% CI: 22–51).1,19 Selected secondary endpoints: MRD response rate during the first two cycles of treatment, RFS, OS, HSCT after BLINCYTO®-induced remission.1,19

BLINCYTO® is an effective treatment for Ph(+) B-cell precursor ALL1

CR/CRh* was achieved for about a third of patients1

Primary endpoint: CR/CRh* rate within the first 2 treatment cycles1,19

Primary endpoint: CR/CRh rate within the first 2 treatment cycles Primary endpoint: CR/CRh rate within the first 2 treatment cycles

CR was defined as 5% blasts in the BM, no evidence of disease, and full recovery of peripheral blood counts (platelets > 100,000/mcL and ANC > 1,000/mcL).1

CRh* was defined as 5% blasts in the BM, no evidence of disease, and partial recovery of peripheral blood counts (platelets > 50,000/mcL and ANC > 500/mcL).1

Consistent response across subgroups1,19

40%

(n=4/10)

CR among patients with T315I mutation

47%

(n=8/17)

CR/CRh* rate among patients treated with
≥ 3 prior TKIs

35%

(n=8/23)

CR/CRh* rate among patients who had received prior ponatinib therapy

  • 31% of responders (n=5/16) proceeded to HSCT1

CR/CRh* in these subgroups was a prespecified analysis in ALCANTARA; however, the CR/CRh* efficacy in these subgroups was not a study objective and the study was not powered to assess CR/CRh* efficacy in these subgroups.20

Response in this subgroup is a post hoc analysis in ALCANTARA, thus the efficacy in this subgroup was not a study objective and the study was not powered to assess efficacy in this subgroup.20

ALL, acute lymphoblastic leukemia; ANC, absolute neutrophil count; BM, bone marrow; CI, confidence interval; CR, complete remission; CRh*, complete remission with partial hematologic recovery; HSCT, allogeneic hematopoietic stem cell transplantation; MRD, measurable or minimal residual disease; NCCN, National Comprehensive Cancer Network; OS, overall survival; Ph(+), Philadelphia chromosome–positive; RFS, relapse-free survival; R/R, relapsed or refractory; TKI, tyrosine kinase inhibitor.

The majority of patients who achieved CR/CRh* with BLINCYTO® had a complete MRD response1,19

88%

(n=14/16)

of patients with CR/CRh* were MRD negative within
the first 2 treatment cycles1,19

  • MRD response was defined as MRD1 by PCR < 1 x 10-4
  • All patients with the T315I mutation who achieved CR/CRh* (n=4/10) were MRD negative within the first 2 treatment cycles19
See the safety data from the ALCANTARA study

PCR, polymerase chain reaction.

ALCANTARA study design and baseline characteristics of patients

ALCANTARA study design: BLINCYTO® single-agent immunotherapy was evaluated in an open-label, single-arm, multicenter phase 2 study (N=45) in adult patients with Ph(+) R/R B-cell precursor ALL who progressed after, or were intolerant to second- or later-generation TKI therapy and were intolerant or refractory to imatinib.1,19

BLINCYTO® single-agent immunotherapy19

  • Continuous IV infusion for 2 induction cycles followed by up to 3 consolidation cycles
  • Treatment cycle: 4 weeks on drug, 2 weeks off
  • Dosing: 9 mcg/day on days 1–7 and 28 mcg/day on days 8–28 for cycle 1, and 28 mcg/day on days 1–28 for subsequent cycles

Primary endpoint:19

  • CR/CRh* during first two cycles

Selected secondary endpoints:19

  • MRD response rate during the first two cycles of treatment
  • RFS
  • OS
  • HSCT after BLINCYTO®-induced remission
Key inclusion criteria19
Patients ≥ 18 years of age
Relapsed after or refractory to at least 1 second- or later-generation TKI or intolerant to second- or later-generation TKI and intolerant or refractory to imatinib
> 5% BM blasts
ECOG performance status ≤ 2
Key exclusion criteria19
HSCT within 12 weeks
Active acute or chronic Grade 2 to 4 GvHD
Systemic treatment of GvHD within 2 weeks before treatment start
History or presence of clinically relevant CNS pathology
Active CNS ALL
Isolated extramedullary disease

Difficult-to-treat patient population

  • BLINCYTO® was evaluated in difficult-to-treat patients, including those with prior ponatinib exposure, T315l mutation, and prior HSCT19

Baseline demographic and disease characteristics (N=45)1,19

Sex, n (%)
Male 24 (53)
Age group, n (%)
18 to < 55 years 22 (49)
55 to < 65 years 11 (24)
65 years 12 (27)
Prior TKI exposure, n (%)
Dasatinib 39 (87)
Imatinib 25 (56)
Ponatinib 23 (51)
Nilotinib 16 (36)
T315I mutation, n (%) 10 (27)§
Prior HSCT, n (%) 20 (44)
≥ 2 prior TKI treatments, n (%) 38 (84)
≥ 3 prior TKI treatments, n (%) 17 (38)

Prior TKI use was not mutually exclusive.19

One patient was resistant to imatinib and was never exposed to a second-generation or later TKI (protocol deviation).19

§Of 37 patients evaluable for TKI mutational analysis.19

CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; GvHD, graft versus host disease; IV, intravenous.

NCCN Guidelines recommend blinatumomab (BLINCYTO®) for adult patients with Ph(+) R/R B-cell precursor ALL7

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.

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
References: 1. BLINCYTO® (blinatumomab) prescribing information, Amgen. 2. 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. 3. Gökbuget N, Zugmaier G, Dombret H, et al. Curative outcomes following blinatumomab in adults with minimal residual disease B-cell precursor acute lymphoblastic leukemia. Leuk Lymphoma. 2020;61:2665-2673. 4. Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-precursor acute lymphoblastic leukemia. Blood. 2018;131(suppl):1522-1531. 5. Data on file, Amgen; 2018. 6. Food and Drug Administration. BLINCYTO® (blinatumomab) for minimal residual disease positive (MRD+) B-cell precursor acute lymphoblastic leukemia (ALL). https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM603411.pdf. Accessed June 30, 2021. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia v.1.2023. ©National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 2, 2023. 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. Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836-847. 9. Dombret H, Topp MS, Schuh A, et al. Blinatumomab versus chemotherapy in first salvage or in later salvage for B-cell precursor acute lymphoblastic leukemia. Leuk Lymphoma. 2019;60:2214-2222. 10. Data on file, Amgen; 2014. 11. Rambaldi A, Huguet F, Zak P, et al. Maintenance therapy with blinatumomab in adults with relapsed/refractory B-precursor acute lymphoblastic leukemia: overall survival in adults enrolled in a phase 3 open-label trial. Presented at: 59th ASH Annual Meeting and Exposition; December 9–12, 2017; Atlanta, GA. Abstract 2552. 12. Topp MS, Zimmerman Z, Cannell P, et al. Health-related quality of life (HRQoL) of blinatumomab versus standard of care (SOC) chemotherapy in patients with relapsed or refractory Philadelphia negative B-cell precursor acute lymphoblastic leukemia in a randomized, open-label phase 3 study (TOWER). Blood. 2016;128:222. 13. Data on file, Amgen; 2017. 14. Data on file, Amgen; 2016. 15. European Organisation for Research and Treatment of Cancer. EORTC QLQ-C30 (version 3). https://www.eortc.org/app/uploads/sites/2/2018/08/Specimen-QLQ-C30-English.pdf. Accessed July 5, 2022. 16. Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(suppl):836-847. 17. Kantarjian H, DeAngelo D, Stelljes M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016; 375:740-753. 18. Data on file, Amgen; 2021. 19. Martinelli G, Boissel N, Chevallier P, et al. Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome–positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol. 2017;35:1795-1802. 20. Data on file, Amgen; [2]; 2014. 21. ClinicalTrials.gov. Blinatumomab in adults with relapsed/refractory Philadelphia positive B-precursor acute lymphoblastic leukemia. https://clinicaltrials.gov/ct2/show/NCT02000427. Accessed September 20, 2021.
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