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
The content of the linked site is the sole responsibility of the site provider. Amgen Inc. does not control or endorse this third-party website.
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.
E1910, the study in adult patients with Ph(–) B-cell precursor ALL in frontline consolidation: A multinational, randomized, controlled, phase 3 trial of BLINCYTO® alternating with chemotherapy vs chemotherapy alone in frontline consolidation in 224 newly diagnosed patients aged 30–70 years with Ph(–) B-cell precursor ALL. OS was calculated from time of randomization until death due to any cause.1,2 3-year KM estimates for OS (primary endpoint) were 84.8% in the BLINCYTO® arm (n=112) vs 69.0% in the chemotherapy only arm (n=112); HR: 0.42 (95% CI: 0.24–0.75);* P = 0.003 (the stratified log-rank test). Median follow-up was 3.6 years in both arms.1 5-year KM estimates for OS were 82.4% in the BLINCYTO® arm (n=112) vs 62.5% in the chemotherapy only arm (n=112); HR: 0.44 (95% Cl: 0.25–0.76).1,†
*The hazard ratio estimates are obtained from a stratified Cox regression model at the third interim analysis.1
†In a later analysis with a median follow-up of 4.5 years.1
Study design: An international, randomized, controlled, phase 3 trial of BLINCYTO® alternating with chemotherapy vs chemotherapy alone in the frontline consolidation phase among 1,440 pediatric patients aged 1 to < 10 years with newly diagnosed Ph(–) NCI standard risk (SR) B-cell precursor ALL who have average or higher risk features.3,* 3-year DFS (primary endpoint) was 96.0% in the BLINCYTO® arm (n=718) vs 87.9% in the chemotherapy only arm (n=722); HR: 0.39 (95% CI: 0.24–0.64):† P < 0.0001.3,4 Median follow-up was 2.5 years. Select secondary endpoints: OS, CIR.3
*SR-Favorable was defined as having all of the following: Favorable genetics (ETV6::RUNX1 fusion or double trisomies of chromosomes 4 and 10), CNS1/2, peripheral blood MRD < 1% at induction day 8, and bone marrow MRD < 0.01% at end of induction. SR-High was defined as having one or more of the following: Unfavorable genetics (iAMP21, KMT2A rearrangement, hypodiploidy (< 44 chromosomes and/or DNA index < 0.81), or t(17;19)(q21-q22;p13.3) or resultant E2A::HLF fusion transcript), end of induction MRD ≥ 0.1% and double trisomies of chromosomes 4 and 10, end of induction bone marrow MRD ≥ 0.01% and not double trisomies of chromosomes 4 and 10, and/or neutral genetics and CNS2. SR-Average was defined as not being SR-Favorable or SR-High.3,5
†The hazard ratio is > 1 for approximately 2 months post randomization, after which it crosses to < 1 for the duration of the follow-up period, with evidence of increasing effect over time.5
Consistent with efficacy observed in adult and AYA patients in the E1910 study1,3
Primary endpoint: DFS* (SR-Average and SR-High)3,4
In the overall cohort, 3-year OS was 98.4% in the BLINCYTO® arm (n=718) vs 97.1% in the chemotherapy only arm (n=722)3
*DFS was defined as the time from randomization to a first event (relapse, a second malignant neoplasm, or death), with data censoring at the date of the last contact.3
†The hazard ratio is > 1 for approximately 2 months post randomization, after which it crosses to < 1 for the duration of the follow-up period, with evidence of increasing effect over time.5
‡Relapse, second malignant neoplasm, or death.3
ALL, acute lymphoblastic leukemia; AYA, adolescent and young adult; CD, cluster of differentiation; CI, confidence interval; CIR, cumulative incidence of relapse; CNS, central nervous system; COG, Children's Oncology Group; DFS, disease-free survival; HR, hazard ratio; KM, Kaplan-Meier; MRD, measurable or minimal residual disease; NCI, National Cancer Institute; OS, overall survival; Ph(–), Philadelphia chromosome–negative; R/R, relapsed or refractory; SR, standard risk.
When integrated into the frontline consolidation phase vs chemotherapy alone
Cumulative Incidence of Relapse (CIR):* SR-Average and SR-High3
*Cumulative incidence of relapse is the estimated incidence of relapse over time.6
SR, standard risk.
COG AALL1731 study design: An international, randomized, controlled, phase 3 trial of BLINCYTO® alternating with chemotherapy vs chemotherapy alone in the frontline consolidation phase among 1,440 pediatric patients aged 1 to < 10 years with newly diagnosed Ph(–) NCI standard risk (SR) B-cell precursor ALL.3
*SR-Favorable was defined as having all of the following: Favorable genetics (ETV6::RUNX1 fusion or double trisomies of chromosomes 4 and 10), CNS1/2, peripheral blood MRD < 1% at induction day 8, and bone marrow MRD < 0.01% at end of induction. SR-High was defined as having one or more of the following: Unfavorable genetics (iAMP21, KMT2A rearrangement, hypodiploidy (< 44 chromosomes and/or DNA index < 0.81), or t(17;19)(q21-q22;p13.3) or resultant E2A::HLF fusion transcript), end of induction MRD ≥ 0.1% and double trisomies of chromosomes 4 and 10, end of induction bone marrow MRD ≥ 0.01% and not double trisomies of chromosomes 4 and 10, and/or neutral genetics and CNS2. SR-Average was defined as not being SR-Favorable or SR-High.3,5
†Does not include patients who had undetectable HTS MRD at the end of induction.3
‡Does not include patients who had MRD between 0.1% and 1% at the end of consolidation.3
§BLINCYTO® was administered as a continuous IV infusion at 15 mcg/m2/day for 28 days.5
| Key inclusion criteria3 |
|---|
| Pediatric patients aged 1 to < 10 years at diagnosis |
| Newly diagnosed Ph(–) SR B-cell precursor ALL |
| WBC count < 50,000/μL |
| Key exclusion criteria7 |
| Secondary ALL after treatment of prior malignancy with chemotherapy |
| Non-DS B-cell precursor ALL with CNS3 leukemia |
| Non-DS B-cell precursor ALL with testicular leukemia |
**Percentages may not total 100 due to rounding.3
††CNS1 defined as no leukemic blasts per cytologic evaluation. CNS2 defined as < 5 white cells per microliter and presence of blasts or traumatic lumbar puncture with presence of blasts per cytologic evaluation but absence of blasts per means of Steinherz–Bleyer algorithm.3
ALL, acute lymphoblastic leukemia; CNS, central nervous system; COG, Children’s Oncology Group; DS, Down syndrome; HTS, high-throughput sequencing; IV, intravenous; MRD, measurable or minimal residual disease; NCI, National Cancer Institute; Ph(–), Philadelphia chromosome–negative; SR, standard risk; WBC, white blood cell count.
See safety data from COG AALL1731
Learn moreStudy design: A randomized, controlled, open-label, phase 3 study of BLINCYTO® vs chemotherapy in 111 patients 28 days to 18 years of age with high-risk,* first-relapsed, Ph(–) B-cell precursor ALL with < 25% blasts in the bone marrow after induction and 2 cycles of consolidation chemotherapy.† Patients were randomized to receive BLINCYTO®‡ or the IntReALL HR 2010 HC3 intensive combination chemotherapy§ as the third cycle of consolidation. Patients were to proceed to HSCT after this cycle of consolidation. Efficacy was established on the basis of OS and RFS. 5-year KM estimates for OS were 78.4% in the BLINCYTO® arm (n=54) vs 41.4% in the chemotherapy only arm (n=57); HR: 0.35 (95% CI: 0.17–0.70). 5-year KM estimates for RFS were 61.1% in the BLINCYTO® arm (n=54) vs 27.6% in the chemotherapy only arm (n=57); HR: 0.38 (95% CI: 0.22–0.66).1
*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.8
†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.9
‡Patients in the BLINCYTO® arm received one cycle of BLINCYTO® as a continuous IV infusion at 15 mcg/m2/day over 4 weeks (maximum daily dose was not to exceed 28 mcg/day).1
§Third block of consolidation chemotherapy, HC3, included: dexamethasone IV/vincristine IV/daunorubicin IV/methotrexate IV/ifosfamide IV/PEG-asparaginase IV/IM.8,10
OS for BLINCYTO® vs chemotherapy1
RFS for BLINCYTO® vs chemotherapy1
*Months were calculated as days from randomization date to event/censor date, divided by 30.5.1
†The hazard ratio estimates are obtained from the Cox proportional hazard model.1
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; 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; OS, overall survival; Ph(–), Philadelphia chromosome–negative; RFS, relapse-free survival; R/R, relapsed or refractory.
| Key inclusion criteria1 |
|---|
| Ph(–) B-cell precursor ALL in high-risk first relapse |
| < 25% blasts in the BM |
| Key exclusion criteria11 |
| 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 |
*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.8
†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.9
‡Third block of consolidation chemotherapy, HC3, included: dexamethasone IV/vincristine IV/daunorubicin IV/methotrexate IV/ifosfamide IV/PEG-asparaginase IV/IM.8,10
§CNS2, patients with WBC count in CSF < 5 per microliter and having blasts in the CSF; CNS3, patients with WBC count in CSF ≥ 5 per microliter and having blasts in the CSF, or clinical/radiographic signs of central nervous leukemia.12
CNS, central nervous system; CSF, cerebrospinal fluid; MRD, measurable or minimal residual disease; PCR, polymerase chain reaction; WBC, white blood cell.
See the full safety profile of the Amgen 20120215 study
Learn moreStudy 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.13
*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.13
†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.13
‡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.12,15
§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.13
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; MRD, measurable or minimal residual disease; OS, overall survival; Ph(–), Philadelphia chromosome–negative; R/R, relapsed or refractory.
IR* and HR† relapse
(HR: 0.70 [95% CI: 0.47–1.03]; P = 0.03)‡
‡The difference was not statistically significant.13
*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.13
†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.13
LR§ relapse
§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. 13
AYA, adolescent and young adult.
| Key inclusion criteria13 |
|---|
| B-cell precursor ALL in first relapse |
| Key exclusion criteria13 |
| Down syndrome |
| Ph(+) B-cell precursor ALL |
| Previous HSCT or BLINCYTO® treatment |
Baseline characteristics of patients in HR or IR first relapse13
| 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.13
†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.13
‡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.12,15
§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.13
HR, high risk; IR, intermediate risk; Ph(+), Philadelphia chromosome–positive.
See the safety results of BLINCYTO® vs chemotherapy in COG AALL1331 in HR or IR first relapse
Learn moreStudy 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).1,17
Within the First Two Treatment Cycles of BLINCYTO®
| Key inclusion criteria17 |
|---|
| 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 criteria17 |
| Active acute or extensive chronic GvHD after HSCT |
| Evidence of active CNS involvement |
| Evidence of active testicular involvement |
Baseline Characteristics (N=70)17,*
| 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) |
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®.1,18,*
*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.19
‡Defined as < 5% blasts in the bone marrow.19
ALL, acute lymphoblastic leukemia; CR1, first complete remission; CR2, second complete remission; CR, complete remission; MRD, measurable or minimal residual disease; NCCN, National Comprehensive Cancer Network; R/R, relapsed or refractory.
Frontline consolidation and R/R: The National Comprehensive Cancer Network® (NCCN®) recommends blinatumomab for Pediatric ALL as a treatment option across lines of therapy in patients with B-cell precursor ALL with:21
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
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.
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.
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.
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:
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. Litzow MR, Sun Z, Mattison RJ, et al. Blinatumomab for MRD-negative acute lymphoblastic leukemia in adults. N Engl J Med. 2024;391:320-333. 3. Gupta S, Rau RE, Kairalla JA, et al. Blinatumomab in standard-risk B-cell acute lymphoblastic leukemia in children. N Engl J Med. Published online December 7, 2024. doi:10.1056/NEJMoa2411680. 4. Rau R, Gupta S, Kairalla J, Rabin K, Loh M, Raetz E. Blinatumomab added to chemotherapy improves disease-free survival in newly diagnosed NCI standard risk pediatric B-acute lymphoblastic leukemia: Results from Children’s Oncology Group Study AALL1731. Presented at: 66th ASH Annual Meeting and Exposition; December 7–10, 2024; San Diego, CA. 5. Gupta S, Rau RE, Kairalla JA, et al. Blinatumomab in standard-risk B-cell acute lymphoblastic leukemia in children. N Engl J Med. Published online December 7, 2024 (suppl). doi:10.1056/NEJMoa2411680. 6. Brazauskas R, Eapen M, Wang T. Endpoint selection and evaluation in hematology studies. Best Pract Res Clin Haematol. 2023;36:101479. 7. Gupta S, Rau RE, Kairalla JA, et al. Blinatumomab in standard-risk B-cell acute lymphoblastic leukemia in children. N Engl J Med. Published online December 7, 2024 (protocol). doi:10.1056/NEJMoa2411680. 8. Data on file, Amgen; 2020. 9. 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. 10. 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 3):843-854. 11. 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. 12. 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. 13. 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. 14. 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. 15. 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. 16. 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. 17. 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. 18. 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. 19. 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. 20. 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 3, 2025. 21. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Acute Lymphoblastic Leukemia V.2.2025. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed January 3, 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.
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
