Role of Inotuzumab Ozogamicin in the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia

George, Binsah; Kantarjian, Hagop M.; Jabbour, Elias; Jain, Nitin

doi:10.2217/imt.15.108

Cited by 17 publications

(15 citation statements)

References 46 publications

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“…In preclinical models of ALL and NHL, inotuzumab ozogamicin was 39 times more potent than unconjugated calicheamicin. 16 , 19 Taken together, the results of these preclinical studies provided the basis for the development of inotuzumab ozogamicin as a potential therapeutic approach for patients with relapsed or refractory B-cell ALL.…”

Section: Preclinical Investigationmentioning

confidence: 99%

See 1 more Smart Citation

Inotuzumab ozogamicin: a CD22 mAb–drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia

Yurkiewicz¹,

Muffly²,

Liedtke³

2018

DDDT

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Despite improved rates of remission and cure in newly diagnosed adult acute lymphoblastic leukemia (ALL), the prognosis for patients with relapsed or refractory disease remains poor and the 5-year overall survival rate after relapse is under 10%. A recent paradigm shift has focused on the promise of targeted immunotherapy rather than standard chemotherapy, as ALL blast cells express a variety of antigens, and monoclonal antibodies may be developed to identify and destroy the leukemic cells. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin. CD22 expression is detected on leukemic blasts in over 90% of patients with ALL. Based on promising results from preclinical studies, inotuzumab ozogamicin was tested in Phase 1/2 and Phase 3 clinical trials and it demonstrated improved complete remission rates, progression-free survival and overall survival in relapsed or refractory adult ALL compared to standard therapy. Ongoing studies are evaluating the value of inotuzumab ozogamicin when given in combination with chemotherapy as part of upfront treatment. This review discusses the drug’s biochemical properties and mechanism of action, preclinical research outcomes, clinical trial results, adverse events and toxicities, drug approval and ongoing investigations.

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Section: Preclinical Investigationmentioning

confidence: 99%

“… 16 – 18 Another biochemical advantage is that compared to other B-lymphoid lineage surface antigens, CD22 is a better internalizing molecule. 16 , 19 …”

Section: Mechanism Of Action and Pharmacokinetic Propertiesmentioning

confidence: 99%

Inotuzumab ozogamicin: a CD22 mAb–drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia

Yurkiewicz¹,

Muffly²,

Liedtke³

2018

DDDT

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“…It is generally advised that length of INO therapy should be limited. Longer spacing from end of INO therapy to AlloSCT is also being studied, such as adding blinatumomab as consolidation prior to AlloSCT [79,80].…”

Section: Clinical Trials Of Inotuzumab Ozogamicin In Allmentioning

confidence: 99%

“…All VOD cases had received clofarabine based conditioning regimens with or without busulfan. For patients who are candidates for AlloSCT, treatment with INO should be limited to 2 cycles of induction or the fewest number of cycles required to achieve a CR/CRi (if CR/CRi not achieved after 2 cycles) [55,79,80].…”

Section: Clinical Trials Of Inotuzumab Ozogamicin In Allmentioning

confidence: 99%

Inotuzumab ozogamicin in clinical development for acute lymphoblastic leukemia and non-Hodgkin lymphoma

Aujla

Liu

2019

Biomark Res

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B cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) frequently express CD19, CD20 and CD22 on the cell surfaces. Immunotherapeutic agents including antibodies and chimeric antigen receptor T cells are widely studied in clinical trials. Several antibody-drug conjugates (ADC) have been approved for clinical use (gemtuzumab ozogamicin in acute myeloid leukemia and brentuximab vedotin in Hodgkin lymphoma as well as CD30+ anaplastic large cell lymphoma). Inotuzumab ozogamicin (INO), a CD22 antibody conjugated with calicheamicin is one of the newest ADCs. INO has been approved for treatment of relapsed /refractory B cell precursor ALL. Multiple ongoing trials are evaluating its role in the relapsed /refractory B cell NHL. This review summarized recent development in INO applications for ALL and NHL.

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“…Inotuzumab ozogamicin is a humanized anti-CD22 monoclonal antibody bound to a toxic natural calicheamicin. 5 The first phase II study with inotuzumab ozogamicin conducted by Kantarjian et al 6 provided patients with heavily pretreated ALL the opportunity to proceed to allogeneic SCT. Inotuzumab is generally well tolerated, although there is a significant incidence of veno-occlusive disease, especially in patients with prior or subsequent SCT.…”

Section: Standard Treatment Approaches For Relapsed and Refractory Allmentioning

confidence: 99%

Emerging Treatment Options for Acute Lymphoblastic Leukemia: Focus on CAR T-Cell Therapy

Brown

Shah

2018

J Natl Compr Canc Netw

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Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of diseases with different morphologic, cytogenetic, and molecular subgroups, some of which have significant therapeutic implications. It typically presents with an aggressive clinical course, and among adults, responds poorly to standard chemotherapy, and carries a high risk for relapse. Despite the significant progress made in inducing remission, frequent relapses remain a challenge. Novel drugs, such as potent later-generation tyrosine kinase inhibitors, antibody-drug conjugates, bispecific monoclonal antibodies, and chimeric antigen receptor (CAR) T-cell therapies, are being investigated in patients with ALL. This summary describes therapies currently approved for the treatment of patients with ALL, identifies emerging targeted immunotherapies for patients with ALL, and discusses adverse events and mechanisms of resistance.

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Role of Inotuzumab Ozogamicin in the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia

Cited by 17 publications

References 46 publications

Inotuzumab ozogamicin: a CD22 mAb–drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia

Inotuzumab ozogamicin: a CD22 mAb–drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia

Inotuzumab ozogamicin in clinical development for acute lymphoblastic leukemia and non-Hodgkin lymphoma

Emerging Treatment Options for Acute Lymphoblastic Leukemia: Focus on CAR T-Cell Therapy

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Role of Inotuzumab Ozogamicin in the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia

Cited by 17 publications

References 46 publications

Inotuzumab ozogamicin: a CD22 mAb&ndash;drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia

Inotuzumab ozogamicin: a CD22 mAb&ndash;drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia

Inotuzumab ozogamicin in clinical development for acute lymphoblastic leukemia and non-Hodgkin lymphoma

Emerging Treatment Options for Acute Lymphoblastic Leukemia: Focus on CAR T-Cell Therapy

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Product

Resources

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Inotuzumab ozogamicin: a CD22 mAb–drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia

Inotuzumab ozogamicin: a CD22 mAb–drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia