BLINCYTO® is indicated for the treatment of relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children.
Study design: International, open-label, single-arm, phase 1/2 study of single-agent BLINCYTO® in patients < 18 years of age with > 25% BM blasts who were primary refractory, in first relapse after full salvage induction, in second or later relapse, or in any relapse after HSCT. Primary endpoint was CR/CRh* in first 2 cycles: 33% (n=23/70); (95% CI: 22.1–45.1).3,4
Within the First Two Treatment Cycles of BLINCYTO®
|Key inclusion criteria4|
|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 criteria4|
|Active acute or extensive chronic GvHD after HSCT|
|Evidence of active CNS involvement|
|Evidence of active testicular involvement|
Baseline Characteristics (N=70)4,‡
|Sex, n (%)|
|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)|
|≥ 3||8 (11)|
|Previous HSCT, n (%)||40 (57)|
|Baseline BM blasts, n (%)|
|< 50%||18 (26)|
|≥ 50%||52 (74)|
Study design: a randomized, controlled, open-label, phase 3 study of BLINCYTO® vs chemotherapy as post-reinduction consolidation therapy prior to HSCT in 108 pediatric patients > 28 days and < 18 years of age with Ph(–) B-cell precursor ALL in high-risk first relapse.§ After receiving reinduction chemotherapy followed by 2 blocks of high-risk consolidation chemotherapy,** patients were randomized to receive one cycle of BLINCYTO® (n=54) or a third block of high-risk consolidation chemotherapy (n=54).†† Primary endpoint was EFS: 66% at 2 years for patients on BLINCYTO® (n=54) vs 27% for patients receiving chemotherapy (n=54); P < 0.001; HR: 0.33 (95% CI: 0.18–0.61). Selected secondary endpoints: OS, incidence of relapse, MRD response, incidence of AEs.1
The Amgen 20120215 study is not in the USPI but was deemed to be consistent with the label for BLINCYTO® use in relapsed or refractory CD19-positive B-cell precursor ALL for the pediatric population.
§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.6
**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.1
††Third block of consolidation chemotherapy, HC3, included: dexamethasone IV/vincristine IV/daunorubicin IV/methotrexate IV/ifosfamide IV/PEG-asparaginase IV/IM.1
EFS for BLINCYTO® vs chemotherapy1
Patients who did not achieve remission or died before assessment were assigned one day of event-free survival. Patients alive and event free were censored on their last assessment date.
AE, adverse event; EFS, event-free survival; EM, extramedullary; HC1, high-risk consolidation block 1; HC2, high-risk consolidation block 2; HC3, high-risk consolidation block 3; HR, hazard ratio; iBM, isolated bone marrow; iEM, isolated extramedullary; IM, intramuscular; MRD, measurable or minimal residual disease; OS, overall survival; Ph(–), Philadelphia chromosome-negative.
of patients who received BLINCYTO® achieved MRD(–)‡‡ vs 54% (n=26/48) of patients who received chemotherapy1
‡‡MRD < 10–4, evaluated in a central laboratory by PCR.1
PCR, polymerase chain reaction.
|Key inclusion criteria1|
|High-risk B-cell precursor ALL in first relapse|
|< 5% blasts or between 5%–25% blasts in BM|
|Key exclusion criteria1|
|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|
|Age at enrollment (years)
|6 (1–17)||5 (1–17)|
|1–9||39 (72.2)||38 (70.4)|
|10–18||15 (27.8)||16 (29.6)|
|Female||24 (44.4)||32 (59.3)|
|Male||30 (55.6)||22 (40.7)|
|Genetic abnormalities at diagnosis of first high-risk relapse|
|Prognosis undefined||5 (9.3)||6 (11.1)|
aOne patient in the blinatumomab group with IAMP21 and one patient in the consolidation chemotherapy group with t(17;19)(q22;p13)/TCF3-HLF also carried a genetic abnormality predicting an unfavorable prognosis.1
Study design: a randomized, controlled, open-label, phase 3 study of 208 patients 1–27 years of age with Ph(–) B-cell precursor ALL in high-risk*** or intermediate-risk first relapse of B-cell precursor ALL.†††,‡‡‡ Following one UKALLR3 reinduction chemotherapy block, patients in the high-risk and intermediate-risk groups were randomized to receive cycles 1 and 2 of BLINCYTO® (n=105) as post-reinduction consolidation therapy or blocks 2 and 3 of chemotherapy consolidation (n=103) based on the UKALLR3 trial.§§§ The primary endpoint was DFS: 54% at 2 years for patients receiving BLINCYTO® (n=105) vs 39% for patients receiving chemotherapy (n=103); P = 0.03; HR: 0.70 (95% CI: 0.47–1.03). Secondary endpoint: OS, exploratory endpoint: MRD response, post hoc endpoint: ability to proceed to HSCT.2
The COG AALL1331 study is not in the USPI but was deemed to be consistent with the label for BLINCYTO® use in relapsed or refractory CD19-positive B-cell precursor ALL for the pediatric and AYA populations.
COG, Children's Oncology Group; DFS, disease-free survival; HSCT, hematopoietic stem cell transplantation; IT, intrathecal.
MRD response after cycle 1 of BLINCYTO® vs block 2 of chemotherapy2,††††
of patients who received BLINCYTO® achieved MRD(–) vs 32% (n=33/103) of patients who received chemotherapy§§§§
More patients who received BLINCYTO® proceeded to HSCT vs those who received chemotherapy2
††††All patients received one block of chemotherapy prior to randomization. Data reflect MRD response for patients who received the first cycle of BLINCYTO® in the BLINCYTO® treatment arm vs patients who received the second block of chemotherapy in the chemotherapy treatment arm.2
‡‡‡‡MRD < 0.01%, evaluated in a central laboratory by flow cytometry.2
§§§§In this analysis, positive MRD or no MRD data are considered as not having negative MRD. The rationale for including patients with no MRD data is that the lack of MRD data was due to death, relapse, or removal from protocol therapy because of an AE or other poor response to therapy, so it is appropriate to include them as the converse of the optimal outcome of being able to submit a sample and have negative MRD.2
Ability to proceed to HSCT
|Key inclusion criteria2|
|B-cell precursor ALL in first relapse|
|Key exclusion criteria2|
|Ph(+) B-cell precursor ALL|
|Previous HSCT or BLINCYTO® treatment|
|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)|
|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|
Hyperdiploid with +4, +10, No.
HR, high risk; IR, intermediate risk; Ph(+), Philadelphia chromosome–positive.
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide, for BLINCYTO®.
BLINCYTO® is a registered trademark of Amgen Inc.
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
References: 1. 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. 2. 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. 3. BLINCYTO® (blinatumomab) prescribing information, Amgen. 4. 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. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN guidelines®) for Pediatric Acute Lymphoblastic Leukemia V.1.2022. ©National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed June 28, 2022. 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. 6. Data on file, Amgen; 2020. 7. 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 randomised trial. Lancet. 2010;376:2009-2017.