When it comes to drug access, should children be considered small adults? Countering coverage denials of FLT3 inhibitors in children with FLT3‐ITD AML

Knight, Tristan; Taub, Jeffrey W.; Krueger, Joerg

doi:10.1002/pbc.29278

Cited by 2 publications

(1 citation statement)

References 47 publications

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“…FLT3 -ITD is therefore classified as a high-risk form of AML by cooperative groups such as the Children’s Oncology Group (COG), and consolidative allogeneic HSCT is recommended [ 128 ]. The integration of FLT3 inhibition into the modern treatment paradigm has therefore been a major advance, although many difficulties remain in securing access to these agents outside of specific clinical trials [ 129 ].…”

Section: Flt3 Inhibition In Pediatric Flt3-mutated Amlmentioning

confidence: 99%

“FLipping” the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors

Knight

Edwards

Meshinchi

et al. 2022

Cancers

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The treatment of many types of cancers, including acute myeloid leukemia (AML), has been revolutionized by the development of therapeutics targeted at crucial molecular drivers of oncogenesis. In contrast to broad, relatively indiscriminate conventional chemotherapy, these targeted agents precisely disrupt key pathways within cancer cells. FMS-like tyrosine kinase 3 (FLT3)—encoding a critical regulator of hematopoiesis—is the most frequently mutated gene in patients with AML, and these mutations herald reduced survival and increased relapse in these patients. Approximately 30% of newly diagnosed AML carries an FLT3 mutation; of these, approximately three-quarters are internal tandem duplication (ITD) mutations, and the remainder are tyrosine kinase domain (TKD) mutations. In contrast to its usual, tightly controlled expression, FLT3-ITD mutants allow constitutive, “run-away” activation of a large number of key downstream pathways which promote cellular proliferation and survival. Targeted inhibition of FLT3 is, therefore, a promising therapeutic avenue. In April 2017, midostaurin became both the first FLT3 inhibitor and the first targeted therapy of any kind in AML to be approved by the US FDA. The use of FLT3 inhibitors has continued to grow as clinical trials continue to demonstrate the efficacy of this class of agents, with an expanding number available for use as both experimental standard-of-care usage. This review examines the biology of FLT3 and its downstream pathways, the mechanism of FLT3 inhibition, the development of the FLT3 inhibitors as a class and uses of the agents currently available clinically, and the mechanisms by which resistance to FLT3 inhibition may both develop and be overcome.

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Section: Flt3 Inhibition In Pediatric Flt3-mutated Amlmentioning

confidence: 99%

“FLipping” the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors

Knight

Edwards

Meshinchi

et al. 2022

Cancers

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Ensuring access to innovative therapies for children, adolescents, and young adults across Canada: The single patient study experience

Revon‐Rivière

Young

Stephenson

et al. 2023

Paediatrics &Amp; Child Health

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Innovative therapeutic approaches are needed to alleviate the burden of life-limiting, rare, and chronic conditions affecting children, adolescents, and young adults (CAYA). This includes a need for improved access to both clinical research and to non-approved or off-label therapies, together with, ultimately, more therapies achieving regulatory approval in Canada. The single patient study (SPS), also known as an open label individual patient (OLIP) study, was introduced by Health Canada to open access to non-marketed drugs where a clinical trial is not readily available, but the drug is considered too investigational to be managed on a standard Special Access Program. SPS is designed for patients who have a serious or life-threatening condition and have exhausted available treatment options. Our report summarizes this relatively new development in the Canadian regulatory environment and highlights the opportunities and challenges as identified by regulators, pharmaceutical representatives, academic researchers, and patient/parent advocates.

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When it comes to drug access, should children be considered small adults? Countering coverage denials of FLT3 inhibitors in children with FLT3‐ITD AML

Cited by 2 publications

References 47 publications

“FLipping” the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors

“FLipping” the Story: FLT3-Mutated Acute Myeloid Leukemia and the Evolving Role of FLT3 Inhibitors

Ensuring access to innovative therapies for children, adolescents, and young adults across Canada: The single patient study experience

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