Inotuzumab Ozogamicin (InO) Combined with UKALL-R3 Modified Chemotherapy in Pediatric Patients with B-Cell Precursor CD22+ Acute Lymphoblastic Leukemia (BCP-ALL) - Results from the ITCC-059 Phase 1B Trial

Pennesi, Edoardo; Brivio, Erica; Ammerlaan, Anneke C.J.; Jiang, Yilin; Velden, Vincent H.J. van der; Beverloo, Berna; Sleight, Barbara; Rives, Susana; Rubio, C. Díaz de Heredia; Sirvent, Francisco José Bautista; Rubio‐San‐Simón, Alba; Rialland, Fanny; Rizzari, Carmelo; Bielorai, Bella; Petit, Arnaud; Bruno, Bénédicte; Öra, Ingrid; Nilsson, Anna; Engstler, Gernot; Brethon, Benoît; Locatelli, Franco; Zwaan, C. Michel

doi:10.1182/blood-2022-163056

Cited by 2 publications

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“…The 12-month estimated EFS was 58.1%; 14 patients proceeded directly to HSCT and six directly to CAR-T. These outcomes were similar to single agent InO but comparison is limited by small numbers (77). The COG AALL1621 study has also been amended to include a combination chemotherapy cohort where InO at 1.1 mg/m 2 /cycle is combined with an augmented BFM consolidation chemotherapy block incorporating cyclophosphamide, cytarabine, vincristine, and asparaginase; data on this approach has yet to be published.…”

Section: Combination Therapy In Pediatricsmentioning

confidence: 72%

Inotuzumab ozogamicin in B-cell precursor acute lymphoblastic leukemia: efficacy, toxicity, and practical considerations

Rubinstein

O’Brien

2023

Front. Immunol.

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Inotuzumab ozogamicin (InO) is an antibody drug conjugate composed of a humanized monoclonal antibody targeting the cell surface receptor CD22 coupled to a cytotoxic calicheamicin payload via an acid labile linker. InO has shown significant activity in relapsed and refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in both single agent and combination chemotherapy regimens in adult and pediatric trials. Its use in newly diagnosed elderly patients has also been established while clinical trials investigating its use in newly diagnosed pediatric patients and fit adults are ongoing. Notable toxicities include sinusoidal obstruction syndrome (SOS), particularly in patients who undergo hematopoietic stem cell transplantation (HSCT) after InO as well as myelosuppression and B-cell aplasia which confer increased infection risk, particularly in combination with cytotoxic chemotherapy. In the relapsed/refractory (R/R) setting, the planned subsequent curative therapy modality must be considered when using InO to mitigate SOS risk if proceeding to HSCT and account for potential B-cell aplasia if proceeding to chimeric antigen receptor CAR-T therapy. Studies exploring mechanisms of resistance or failure of InO are ongoing but modulation or loss CD22 expression, alternative CD22 splicing, and high Bcl-2 expression have been implicated. In this review, we will summarize the currently available data on InO, with an emphasis on pediatric trials, and explore future directions including combinatorial therapy.

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Section: Combination Therapy In Pediatricsmentioning

confidence: 72%

Inotuzumab ozogamicin in B-cell precursor acute lymphoblastic leukemia: efficacy, toxicity, and practical considerations

Rubinstein

O’Brien

2023

Front. Immunol.

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“…Nevertheless, heavily pretreated patients were included in this trial (after multiple relapses and/or after HSCT) and this might have had an impact on the added value of chemotherapy as well as the liver toxicity. 46 In the front-line setting, InO is also being studied in combination with chemotherapy, using a sequential model. The COG AALL1732 trial is testing InO in a phase III, randomized trial in newly diagnosed, high-risk, CD22-positive BCP-ALL (NCT03959085).…”

Section: Anti-cd22mentioning

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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Inotuzumab Ozogamicin (InO) Combined with UKALL-R3 Modified Chemotherapy in Pediatric Patients with B-Cell Precursor CD22+ Acute Lymphoblastic Leukemia (BCP-ALL) - Results from the ITCC-059 Phase 1B Trial

Cited by 2 publications

References 0 publications

Inotuzumab ozogamicin in B-cell precursor acute lymphoblastic leukemia: efficacy, toxicity, and practical considerations

Inotuzumab ozogamicin in B-cell precursor acute lymphoblastic leukemia: efficacy, toxicity, and practical considerations

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

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