Phase II study of the hyper-CVAD regimen in combination with ofatumumab as frontline therapy for adults with CD-20 positive ALL.

Jabbour, Elias; Kantarjian, Hagop M.; Thomas, Deborah A.; Aad, Simon Abi; Garris, Rebecca; Cortés, Jorge E.; Kadia, Tapan M.; Ravandi, Farhad; Verstovšek, Srđan; O’Brien, Susan

doi:10.1200/jco.2014.32.15_suppl.7065

Cited by 12 publications

(5 citation statements)

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“…One study evaluated ofatumumab added to the Hyper-CVAD regimen as frontline therapy of adult patients with CD20+ ALL. 26 With this regimen, 22 of 23 evaluable patients achieved CR (95%) and were MRD-negative (by flow cytometry) after cycle 1. One-year remission and OS duration was 91%.…”

Section: Naked Antibodiesmentioning

confidence: 96%

Modern Immunotherapy of Adult B-Lineage Acute Lymphoblastic Leukemia With Monoclonal Antibodies and Chimeric Antigen Receptor Modified T Cells

Maino¹,

Scattolin

Viero

et al. 2015

Mediterr J Hematol Infect Dis

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The introduction of newer cytotoxic monoclonal antibodies and chimeric antigen receptor modified T cells is opening a new age in the management of B-lineage adult acute lymphoblastic leukemia. This therapeutic change must be very positively acknowledged because of the limits of intensive chemotherapy programs and allogeneic stem cell transplantation. In fact, with these traditional therapeutic tools the cure can be achieved in only 40–50% of the patients. The failure rates are particularly high in the elderly, in patients with post-induction persistence of minimal residual disease and especially in refractory/relapsed disease. The place of the novel immunotherapeutics in improving the outcome of adult patients with B-lineage acute lymphoblastic leukemia is reviewed.

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Section: Naked Antibodiesmentioning

confidence: 96%

Modern Immunotherapy of Adult B-Lineage Acute Lymphoblastic Leukemia With Monoclonal Antibodies and Chimeric Antigen Receptor Modified T Cells

Maino¹,

Scattolin

Viero

et al. 2015

Mediterr J Hematol Infect Dis

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“…In adults with CD20 ALL, ofatumumab was added to the hyper-CVAD regimen. The 1-year PFS and OS were 91% [22]. Most common grade 3 toxic events were hepatic, thrombosis and neuropathy.…”

Section: Cd20 Directed Therapymentioning

confidence: 97%

The development of targeted new agents to improve the outcome for children with leukemia

Bautista

Kearns

Mussai

et al. 2016

Expert Opinion on Drug Discovery

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Survival rates in pediatric leukemia have greatly improved in the last decades but still a substantial number of patients will relapse and die. New agents are necessary to overcome the limitations of conventional chemotherapy and hematopoietic stem cell transplantation and to reduce their undesirable long-term toxicities. The identification of driving molecular alterations of leukemogenesis in subsets of patients will allow the incorporation of new-targeted therapies. Areas covered: In this article the authors present a detailed review of the most recent advances in targeted therapies for pediatric leukemias. A comprehensive description of the biological background, adult data and early clinical trials in pediatrics is provided. Expert opinion: Clinical trials are the way to evaluate new agents in pediatric cancer. The development of new drugs in pediatric leukemia must be preceded by a solid biological rationale. Agents in development exploit all possible vulnerabilities of leukemic cells. Drugs targeting cell surface antigens, intracellular signaling pathways and cell cycle inhibitors or epigenetic regulators are most prominent. Major advances have occurred thanks to new developments in engineering leading to optimized molecules such as anti-CD19 bi-specific T-cell engagers (e.g. blinatumomab) and antibody-drug conjugates. The integration of new-targeted therapies in pediatric chemotherapy-based regimens will lead to improved outcomes.

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“…Table provides a synopsis of monoclonal antibodies targeting leukemic surface antigens that have regulatory approval as well as key investigational agents: CD33, CD19, CD20, CD22, and CD52 . Of note, rituximab requires the combination with conventional chemotherapy for efficacy, whereas others may be given as a single agent.…”

Section: Acute Lymphoblastic Leukemiamentioning

confidence: 99%

Driving Toward Precision Medicine for Acute Leukemias: Are We There Yet?

Chung

Yu-Heng

2017

Pharmacotherapy

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Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not changed significantly over the last few decades. We present a nonexhaustive summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways. Some of these targets may be used as predictive biomarkers for the development of novel targeted therapies that depart significantly from conventional chemotherapy, the current mainstay for the treatment of acute leukemias. Established leukemia-specific predictive biomarkers for precision medicine include those genetic lesions such as BCR-ABL1 for Philadelphia-positive acute lymphoblastic leukemia and PML-RARα for acute promyelocytic leukemia. Evidence indicates that targeted therapy for FLT-ITD gene mutations with small-molecule tyrosine kinase inhibitors can extend its use from relapsed disease to up-front induction therapy. Core-binding factor acute myeloid leukemia in adults predicts benefit with high-dose cytarabine in the absence of KIT mutation. Although risk-adapted therapy based on genetic abnormalities in acute leukemias has allowed the beginning of personalized treatment and selective use of hematopoietic stem cell transplantation, the prognostic and/or predictive value of many novel mutations of the acute leukemic genome is yet to be elucidated. Many challenges lie ahead in targeted therapies due to overlapping of chromosomal and molecular lesions as well as other limiting factors. Future work should focus on the understanding of pathogenetic changes that lead to leukemogenesis, which may guide the rational design of new targeted therapies and make the drive toward precision medicine for acute leukemias one step closer.

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Phase II study of the hyper-CVAD regimen in combination with ofatumumab as frontline therapy for adults with CD-20 positive ALL.

Cited by 12 publications

References 0 publications

Modern Immunotherapy of Adult B-Lineage Acute Lymphoblastic Leukemia With Monoclonal Antibodies and Chimeric Antigen Receptor Modified T Cells

Modern Immunotherapy of Adult B-Lineage Acute Lymphoblastic Leukemia With Monoclonal Antibodies and Chimeric Antigen Receptor Modified T Cells

The development of targeted new agents to improve the outcome for children with leukemia

Driving Toward Precision Medicine for Acute Leukemias: Are We There Yet?

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