Blinatumomab As Toxicity Sparing First Line Treatment of Children and Young Persons with B-Precursor Acute Lymphoblastic Leukaemia (B-ALL)

Hodder, Angus; Mishra, Avijeet Kumar; Baird, Susan; Bisho, Ismail; Bonney, Denise; Clesham, Katherine; Cummins, Michelle; Dickens, Emmy; Gibson, Brenda; George, Lindsay; Ingham, Danielle; Jigoulina, Galina; Lancaster, Donna; Lindsay, Katherine; Madni, Majid; Malone, Andrea; Mitchell, Bethany; Moppett, John; Jayashree, Muralidharan; Moorman, Anthony V.; Patrick, Katharine; Samrin, Lamia; Tewari, Sanjay; Thakur, Indu; O’Connor, David; Vora, Ajay; Samarasinghe, Sujith

doi:10.1182/blood-2022-162475

Cited by 6 publications

(4 citation statements)

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“…28 A retrospective study on 105 patients showed that the 2-year outcome of patients treated with blinatumomab as replacement for post-remission intensive chemotherapy was comparable to that of the chemotherapy-treated control group, with only one grade 3-4 adverse event occurring in the blinatumomab group. 29 In adults, the ECOG ACRIN E1910 randomized phase III trial showed that patients with newly diagnosed ALL who become MRD-negative (<0.01%) after induction chemotherapy have better survival when they are given four cycles of blinatumomab during consolidation chemotherapy than when they are given only chemotherapy. In contrast, a benefit could not be confirmed in patients who received only one or two cycles of blinatumomab.…”

Section: Resultsmentioning

confidence: 99%

Naked antibodies and antibody-drug conjugates: targeted therapy for childhood acute lymphoblastic leukemia

Brivio,

Bautista,

Zwaan

2024

haematol

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The treatment of childhood acute lymphoblastic leukemia (ALL) has reached overall survival rates exceeding 90%. The present and future challenges are to cure the remainder of patients still dying from disease, and to reduce morbidity and mortality in those who can be cured with standard-of-care chemotherapy by replacing toxic chemotherapy elements while retaining cure rates. With the novel therapeutic options introduced in the last years, including immunotherapies and targeted antibodies, the treatment of ALL is undergoing major changes. For B-cell precursor ALL, blinatumomab, an anti-CD19 bispecific antibody, has established its role in the consolidation treatment for both high- and standard-risk first relapse of ALL, in the presence of bone marrow involvement, and may also have an impact on the outcome of high-risk subsets such as infant ALL and Philadelphia chromosome-positive ALL. Inotuzumab ozogamicin, an anti-CD22 drug conjugated antibody, has demonstrated high efficacy in inducing complete remission in relapsed ALL, even in the presence of high tumor burden, but randomized phase III trials are still ongoing. For T-ALL the role of CD38-directed treatment, such as daratumumab, is gaining interest, but randomized data are needed to assess its specific benefit. These antibodies are currently being tested in patients with newly diagnosed ALL and may lead to major changes in the present paradigm of treatment of pediatric ALL. Unlike the past, lessons may be learned from innovations in adult ALL, in which more drastic changes are piloted that may need to be translated to pediatrics.

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Section: Resultsmentioning

confidence: 99%

Naked antibodies and antibody-drug conjugates: targeted therapy for childhood acute lymphoblastic leukemia

Brivio,

Bautista,

Zwaan

2024

haematol

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“…With 10-30% of CD19-negative relapses, there is a clear need for novel approaches in flow cytometric MRD assessment for BCP-ALL that do not rely on CD19 as the primary B-cell marker (Figure 1). Since novel treatment strategies use Blinatumomab or CAR-T cell therapies even as first-line treatment for BCP-ALL [115][116][117], the number of patients with CD19-negative relapses may even further increase.…”

Section: Immunotherapy and Escape In Bcp-allmentioning

confidence: 99%

The Evolving Landscape of Flowcytometric Minimal Residual Disease Monitoring in B-Cell Precursor Acute Lymphoblastic Leukemia

Verbeek,

van der Velden

2024

IJMS

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Detection of minimal residual disease (MRD) is a major independent prognostic marker in the clinical management of pediatric and adult B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL), and risk stratification nowadays heavily relies on MRD diagnostics. MRD can be detected using flow cytometry based on aberrant expression of markers (antigens) during malignant B-cell maturation. Recent advances highlight the significance of novel markers (e.g., CD58, CD81, CD304, CD73, CD66c, and CD123), improving MRD identification. Second and next-generation flow cytometry, such as the EuroFlow consortium’s eight-color protocol, can achieve sensitivities down to 10−5 (comparable with the PCR-based method) if sufficient cells are acquired. The introduction of targeted therapies (especially those targeting CD19, such as blinatumomab or CAR-T19) introduces several challenges for flow cytometric MRD analysis, such as the occurrence of CD19-negative relapses. Therefore, innovative flow cytometry panels, including alternative B-cell markers (e.g., CD22 and CD24), have been designed. (Semi-)automated MRD assessment, employing machine learning algorithms and clustering tools, shows promise but does not yet allow robust and sensitive automated analysis of MRD. Future directions involve integrating artificial intelligence, further automation, and exploring multicolor spectral flow cytometry to standardize MRD assessment and enhance diagnostic and prognostic robustness of MRD diagnostics in BCP-ALL.

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“…В настоящее время относительно мало работ по применению блинатумомаба у детей с первичным ВП-ОЛЛ [12,18,19,55], особенно у пациентов, отобранных только по скорости клиренса МОБ. В недавно опубликованной работе A. Hodder и соавт.…”

Section: обсуждение результатов исследованияunclassified

“…О Р И Г И Н А Л Ь Н Ы Е С Т А Т Ь И с полученными нами данными и также подтверждающие эффективность блинатумомаба как средства достижения МОБ-негативной ремиссии и улучшения прогноза у пациентов с медленным ответом на терапию [55].…”

Section: а бunclassified

The use of blinatumomab in children with de novo Ph-negative B-lineage acute lymphoblastic leukemia and slow clearance of minimal residual disease

Popov,

Rumyantseva,

Mikhailova

et al. 2024

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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Children with acute lymphoblastic leukemia (ALL) and slow clearance of minimal residual disease (MRD) demonstrate a significantly worse outcome as compared to those with fast response to chemotherapy. Bispecific monoclonal antibody blinatumomab is the key drug for CD19-directed immunotherapy which opens wide opportunities for the elimination of MRD in patients with B-cell precursor ALL (BCP-ALL). Aim of the study – to evaluate the effectiveness of blinatumomab for MRD elimination in children with BCP-ALL and slow MRD clearance treated by the “ALL-MB 2015” protocol. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Patients from the “ALL-MB 2015” trial who demonstrated slow MRD clearance at the end of induction were included in the current study. MRD monitoring was performed by multicolor flow cytometry modified with respect to possible CD19 loss during targeted treatment. Threshold of 0.001% was used for MRD positivity definition. Between February 2020 and August 2023, 228 children with de novo Ph-negative KMT2A-negative BCP-ALL were defined as slow MRD responders according to the criteria of the “Moscow-Berlin” group. Fifty of them were treated with blinatumomab because of slow MRD clearance. Blinatumomab course was given immediately after induction in 23 children, after Consolidation I – in 14 patients, after Consolidation II – in 11 patients, while two children received immunotherapy prior to maintenance. After completion of blinatumomab course, 23 patients continued protocol treatment, 21 received maintenance only, two were treated with high-risk blocks and four received hematopoietic stem cell transplantation. Only 2 of 50 (4.0 %) patients remained MRD-positive after completion of blinatumomab course. By the end of December 2023, only two adverse events were registered: one relapse and one remission death. Two-year event-free survival was 94.7 % (standard error 3.6 %), while cumulative incidence of relapse was 2.6 % (standard error 2.7 %). Outcome in these 50 patients was much better in comparison with 178 children with a slow MRD response who did not receive blinatumomab. The use of blinatumomab in children with de novo Ph-negative BCP-ALL with slow MRD clearance allows achieving MRD-negative remission in nearly all cases. Although a longer follow-up is necessary for the reliable conclusion of CD19-directed therapy effectiveness, the promising results are obtained in the current study in this unfavorable patient group.

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Blinatumomab As Toxicity Sparing First Line Treatment of Children and Young Persons with B-Precursor Acute Lymphoblastic Leukaemia (B-ALL)

Cited by 6 publications

References 0 publications

Naked antibodies and antibody-drug conjugates: targeted therapy for childhood acute lymphoblastic leukemia

Naked antibodies and antibody-drug conjugates: targeted therapy for childhood acute lymphoblastic leukemia

The Evolving Landscape of Flowcytometric Minimal Residual Disease Monitoring in B-Cell Precursor Acute Lymphoblastic Leukemia

The use of blinatumomab in children with de novo Ph-negative B-lineage acute lymphoblastic leukemia and slow clearance of minimal residual disease

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