Targeted Therapy in Acute Lymphoblastic Leukaemia
Ross Salvaris,Pasquale L. Fedele +1 more
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TLDR
A review of the available and emerging targeted therapeutics in ALL, to explore their mechanisms of action and to discuss the current evidence for their use can be found in this article, where the authors highlight a range of available, emerging, and available targeted therapies in ALL.Abstract:
The last decade has seen a significant leap in our understanding of the wide range of genetic lesions underpinning acute lymphoblastic leukaemia (ALL). Next generation sequencing has led to the identification of driver mutations with significant implications on prognosis and has defined entities such as BCR-ABL-like ALL, where targeted therapies such as tyrosine kinase inhibitors (TKIs) and JAK inhibitors may play a role in its treatment. In Philadelphia positive ALL, the introduction of TKIs into frontline treatment regimens has already transformed patient outcomes. In B-ALL, agents targeting surface receptors CD19, CD20 and CD22, including monoclonal antibodies, bispecific T cell engagers, antibody drug conjugates and chimeric antigen receptor (CAR) T cells, have shown significant activity but come with unique toxicities and have implications for how treatment is sequenced. Advances in T-ALL have lagged behind those seen in B-ALL. However, agents such as nelarabine, bortezomib and CAR T cell therapy targeting T cell antigens have been examined with promising results seen. As our understanding of disease biology in ALL grows, as does our ability to target pathways such as apoptosis, through BH3 mimetics, chemokines and epigenetic regulators. This review aims to highlight a range of available and emerging targeted therapeutics in ALL, to explore their mechanisms of action and to discuss the current evidence for their use.read more
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Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome
Brian J. Druker,Charles L. Sawyers,Hagop M. Kantarjian,Debra Resta,Sofia Fernandes Reese,John Ford,Renaud Capdeville,Moshe Talpaz +7 more
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Hagop M. Kantarjian,Charles L. Sawyers,Andreas Hochhaus,François Guilhot,Charles A. Schiffer,Carlo Gambacorti-Passerini,Dietger Niederwieser,Debra Resta,Renaud Capdeville,Ulrike Zoellner,Moshe Talpaz,Brian J. Druker +11 more
TL;DR: Imatinib induced high rates of cytogenetic and hematologic responses in patients with chronic-phase CML in whom previous interferon therapy had failed, and CML had not progressed to the accelerated or blast phases after a median follow-up of 18 months.
Journal ArticleDOI
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia
Jae H. Park,Isabelle Riviere,Mithat Gonen,Xiuyan Wang,Brigitte Senechal,Kevin J. Curran,Craig S. Sauter,Yongzeng Wang,Bianca Santomasso,Elena Mead,Mikhail Roshal,Peter Maslak,Marco L. Davila,Renier J. Brentjens,Michel Sadelain +14 more
TL;DR: A phase 1 trial involving adults with relapsed B‐cell ALL who received an infusion of autologous T cells expressing the 19‐28z CAR at the Memorial Sloan Kettering Cancer Center found that patients with a low disease burden before treatment had markedly enhanced remission duration and survival and had a markedly lower incidence of the cytokine release syndrome and neurotoxic events after infusion.