Rydapt is indicated...in combination with standard daunorubicin and cytarabine induction and high dose cytarabine consolidation chemotherapy, and for patients in complete response followed by Rydapt single agent maintenance therapy, for adult patients with newly diagnosed acute myeloid leukaemia (AML) who are FLT3 mutation positive...

RYDAPT is a kinase inhibitor indicated for the treatment of adult patients with:...Newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation-positive as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation.

Total 301 patients (47.2% >60 years, 82.7% with FLT3-ITDmut) of median age 59 years entered induction phase...Overall, complete remission (CR) rate including incomplete hematological recovery (CR+CRi) (80.7% [95%CI: 75.74, 84.98]) was comparable between age groups (≤60 years [83.5%]; >60 to ≤70 years [82.5%]...Overall, safety and efficacy of midostaurin remains consistent with previous findings...

Final HR for EFS was 1.00 (95% CI, 0.78–1.29); the majority of events in both treatment arms were induction failures (Table). HR for OS was 0.85 (95% CI, 0.57–1.25) in favor of midostaurin. The safety profile of midostaurin was consistent with prior reports (Table)....Results from UNIFY are consistent with the safety/tolerability profile previously reported for midostaurin, but do not show efficacy for midostaurin in FLT3-MN AML; this suggests that the clinical effect of midostaurin in AML is primarily in the FLT3-mutated setting.

Novartis announced today that the United States Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to PKC412 (midostaurin). PKC412 (midostaurin) is an investigational treatment for adults with newly-diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test, and who are eligible to receive standard induction and consolidation chemotherapy.

Overall survival was significantly longer in the midostaurin group than in the placebo group (hazard ratio for death, 0.78; one-sided P=0.009), as was event-free survival (hazard ratio for event or death, 0.78; one-sided P=0.002). In both the primary analysis and an analysis in which data for patients who underwent transplantation were censored, the benefit of midostaurin was consistent across all FLT3 subtypes.

...Documented FLT3 mutation (ITD or point mutation), determined by analysis in a protocol- designated FLT3 screening laboratory...

This is multicentric non-interventional retrospective real-world study including patients 60 years of age with newly diagnosed FLT3-mutated AML treated with intensive chemotherapy and midostaurine (50 mg orally twice daily, d8-22)...The median follow-up of the patients was 32 months. OS for the entire population was 23 months with a 2-years OS of 49.1% (95%CI: 41.5-56.7). Median EFS for the entire population was 11.1 months with a 2-years EFS of 37.1%....This real-life study suggests that the addition of midostaurine to intensive chemotherapy regimens in elderly patients could result in acceptable CRc, OS and EFS.

We retrospectively analysed peripheral blood (PB, n=37) and/or bone marrow (BM, n=34) diagnosis samples of47 FLT3-MP AML patients subsequently treated with M+IC... On the expanded training dataset,including patients with DFS between 6 months and 24 months (n=13), response stratification was achieved...

We performed a single center, retrospective cohort study and analyzed patients who had FLT3+ AML…FLT3i maintenance therapy, including Midostaurin, Sorafenib, and Gilteritinib, was started…when adjusted for the conditioning regimen and donor status, the differences were statistically significant with improvement in OS for patients on FLT3i maintenance (HR 0.42, 95% CI 0.18 to 0.95, p = 0.04).

Regarding responses on those treated with CMT 64% (n=46) obtained Complete Remission (CR), subsequently 37 pts (51%) received consolidation with high doses of CMT, 13 pts relapsed, and 26 received HSCT...Our results in day-to-day practice confirm that midostaurin associated with CMT improved the outcome of FLT3 positive AML patients.

The aims of this study are to analyze safety and effectiveness of Midos plus IC in FLT3 AML….Effectiveness: 144 (81.4%) pt achieved CR after Induction 1or 2...Our experience confirms safety and effectiveness of Midos plus IC as first line in FLT3 AML patients with similar 2yOS as the previous reported in the RATIFY trial.

Overall survival is significantly longer in the mido+IC group than in the IC group (not reached vs 19 months, p=0.022), 24mOS 79.2% vs 54.2% (p0.026)....The results of this study confirm in a real-world setting that midostaurin associated with IC improve the outcome of AML FLT3 positive patient compared versus IC alone.

The rate of BR for the population in whom efficacy could be assessed (n = 92) was 71% in patients with FLT3-mutant and 42% in patients with FLT3 wild-type. One PR occurred in a patient with FLT3-mutant receiving the 100-mg dose regimen. Both doses were well-tolerated; there were no differences in toxicity or response rate according to the dose of midostaurin.

A phase 2b study of midostaurin in AML and MDS patients with either wild-type (n = 60) or mutant (n = 35) FLT3 has been reported.13 Among 92 patients evaluable for response, 71% of FLT3-mutant patients had a ⩾50% reduction in peripheral blood or bone marrow blasts compared to 42% of FLT3-wild-type patients.