Midostauring maintenance for FLT-3 positive AML – pro
Post-transplant maintenance therapy with midostaurin was safe and reduced relapse risk in patients with FLT3-mutated acute myeloid leukemia (AML), according to findings from the phase II RADIUS trial presented at the 2019 Transplantation & Cellular Therapy (TCT) Meetings of the American Society for Blood and Marrow Transplantation (ASBMT) and the Center for International Blood & Marrow Transplant Research (CIBMTR), formerly known as the BMT Tandem Meetings. The results also demonstrated that midostaurin-treated patients who experienced greater inhibition of phosphorylated FLT3 (pFLT3) had a greater likelihood of remaining disease-free. THis was just presented and requires confirmatory studies as well as studies against other post transplant strategies.
A more recent report by Maziarz confirmed that this drug reduces relapses in FLT-3 positive AML patients when used as maintenance.
Maziarz RT, Fernandez H, Patnaik MM, et al. Radius: Midostaurin (mido) plus standard of care (SOC) after allogeneic stem cell transplant (alloSCT) in patients (pts) with FLT3-internal tandem duplication (ITD)–mutated acute myeloid leukemia (AML). Abstract #13. Presented at the Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR, February 20, 2019; Houston, TX.
NCCN, AML 2020
Weisberg, Ellen; Boulton, Christina; Kelly, Louise M; Manley, Paul; Fabbro, Doriano; Meyer, Thomas; Gilliland, D.Gary; Griffin, James D (2002). “Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412″. Cancer Cell. 1 (5): 433–43.
Stone, Richard M.; Mandrekar, Sumithra; Sanford, Ben L; Geyer, Susan; Bloomfield, Clara D.; Dohner, Konstanze; Thiede, Christian; Marcucci, Guido; Lo-Coco, Francesco; Klisovic, Rebecca B.; Wei, Andrew; Sierra, Jorge; Sanz, Miguel A.; et al. (December 2015). The multi-kinase inhibitor midostaurin (M) prolongs survival compared with placebo (P) in combination with daunorubicin (D)/cytarabine (C) induction (ind), high-dose C consolidation (consol), and as maintenance (maint) therapy in newly diagnosed acute myeloid leukemia (AML) patients (pts) age 18–60 with FLT3 mutations (muts): An international prospective randomized (rand) P-controlled double-blind trial (CALGB 10603/RATIFY [Alliance]). American Society of Hematology (ASH) 57th Annual Meeting. Orlando.
Richard T. Maziarz et al, Radius: Midostaurin (mido) Plus Standard of Care (SOC) after Allogeneic Stem Cell Transplant (alloSCT) in Patients (pts) with FLT3-Internal Tandem Duplication (ITD)–Mutated Acute Myeloid Leukemia (AML) BBMT March 2019Volume 25, Issue3, Supplement, Pages S11–S12
Maziarz, R.T., Levis, M., Patnaik, M.M. et al. Midostaurin after allogeneic stem cell transplant in patients with FLT3-internal tandem duplication-positive acute myeloid leukemia. Bone Marrow Transplant 56, 1180–1189 (2021).