TEST:

LeukoStrat® CDx FLT3 Mutation Assay

"Invivoscribe is excited to announce that their CE-2797 IVD certified LeukoStrat CDx FLT3 Mutation Assay has been approved by BSI (Netherlands) and the EMA to aid in the selection of individuals in the European Union and European Economic Area with newly diagnosed FLT3-ITD positive acute myeloid leukemia (AML) who may be eligible to receive treatment with Daiichi Sankyo’s VANFLYTA (quizartinib)...In regions where XOSPATA (gilteritinib fumarate) is available, the LeukoStrat CDx FLT3 Mutation Assay is used as an aid in the assessment of patients with AML for whom XOSPATA (gilteritinib fumarate) treatment is being considered...In regions where VANFLYTA (quizartinib hydrochloride) is available, the LeukoStrat CDx FLT3 Mutation Assay is used as an aid in the assessment of patients with FLT3-ITD+ AML for whom VANFLYTA (quizartinib hydrochloride) treatment is being considered."

Among patients ≥60 yrs with ND AML given LIT, the current 2022 ELN risk system classifies most (79%)patients as adverse risk and does not reliably distinguish favorable from intermediate-risk, highlighting thelimitations of the model in this patient population. We propose a refined LLS classification using a "mutationscore" incorporating IDH2, MLL2, KRAS and TP53 mutations for those previously assigned ELN 2022 adverserisk, as well as redefining the definition of LLS-favorable risk.

Blue indicates positive correlation, red indicated negative correlation. Only significant correlations (p<0.01) are shown.

Background Q-F (NCT02668653) showed that the highly potent, selective, type 2 FLT3 inhibitor quizartinib (Q) + standard chemotherapy ± transplantation, followed by Q monotherapy for ≥36 cycles, reduced the relative risk of death by 22.4% vs placebo (P) in newly diagnosed (nd) FLT3-ITD+ AML, with HR of 0.776 and P value of 0.0324 (PMID: 37116523)...Conclusions This study showed 1) agreement between CDx & CTA in identifying nd FLT3-ITD+ AML pts and 2) that OS benefit provided by Q in the ITT CDx+ population is comparable with the OS benefit in the ITT population of Q-F. The LeukoStrat CDx FLT3 Mutation Assay aids in assessing AML pts for Q therapy.

FLT3 ITDs are associated with higher risk and unfavorable outcomes; however, targeted therapy with midostaurin and gilteritinib has been FDA approved, and detection during diagnosis is critical for initiating timely treatment. Modifications of the final volume of PCR mixes, DNA input, and capillary length do not significantly affect the assay's performance. The described modifications reduce reagents, DNA consumption, and the cost of the assay.

"On July 20, 2023, the Food and Drug Administration approved quizartinib (Vanflyta, Daiichi Sankyo, Inc.) with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive, as detected by an FDA-approved test...FDA also approved LeukoStrat CDx FLT3 Mutation Assay as a companion diagnostic for Vanflyta."

Nineteen patients received intensive chemotherapy and two hypomethylating agents +/- venetoclax (cycles 8-9)... Using NGS techniques in AML NPM1+ patients detects concurrent mutations with potential prognostic significance and can contribute to daily clinical practice. These techniques must be carried out in patients diagnosed with AML who will receive treatment and only in specialized and accredited centers. Molecular markers, Acute myeloid leukemia, Prognostic groups

"'Today we are pleased to announce that Invivoscribe’s LeukoStrat® CDx FLT3 Mutation Assay has been approved by BSI (Netherlands) and the EMA as a Class C CDx assay, meeting the stringent new IVDR (Regulation (EU) 2017/746) requirements. Invivoscribe is one of the first companies in the world to gain an IVDR approval of a CDx assay. IVDR is a set of regulations that came into effect on May 26, 2022 that were put in place by the Europe Union (EU) to ensure the safety, traceability, quality and performance of in-vitro diagnostic medical devices (IVDs),' says Jason Gerhold, Global Director of Regulatory, Quality, and Clinical Affairs at Invivoscribe."

Finally, our study demonstrates that in patients FLT3-ITD positive at diagnosis, ddPCR allows to detect the persistence or the reappearance of small clones that expand until clinical relapse. The possibility of an early diagnosis of molecular relapse offers a window of time for intervention with selective FLT3 inhibitors in the attempt to prevent or delay relapse.

"Invivoscribe is pleased to announce that they have filed a supplemental Pre-Market Approval (sPMA) submission with the U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) for the use of the LeukoStrat^® CDx FLT3 Mutation Assay as the companion diagnostic for Daiichi Sankyo's investigational drug quizartinib. The assay is used for the identification of newly diagnosed acute myeloid leukemia (AML) patients that have the FLT3-ITD mutation....The filing supports Daiichi Sankyo's new drug application (NDA) for quizartinib for the proposed treatment of adult patients with newly diagnosed FLT3-ITD positive AML, which was granted Priority Review by the FDA."

In recent years the US Food and Drug Administration (FDA) has been very active in approving targeted therapeutic drugs for AML patients including Midostaurin (Rydapt; 2017) and Gilteritinib (Xospata;2018) for FLT3 mutations; Enasidenib (Idhifa; 2017) for IDH2 mutations and Ivosidenib (Tibsovo; 2018) for IDH1 mutations. The IDH1 CDx, IDH2 CDx and FLT3 CDx tests are highly sensitive and Versiti provides average turn around time of 3 business days which enable rapid decision making on the recently available drug therapies for AML patients. We strongly recommend that the IDH1 CDx, IDH2 CDx and FLT3 CDx tests should be performed on all AML patients for better care.

"Table. CR, complete remission; CRh, complete remission with partial haematological recovery; ITT, intention-to-treat."

(D) Spiked-in VAF v. detected VAF is shown for FLT3-ITD samples with 30 bp and 126 bp insertions, with spiked-in VAF ranging from 5%–100%. Vertical bars give the VAFs for ROPEs ± 10% of the initial ROPE width, which conveys the sensitivity of each VAF to the ROPE width.