International sentinel site surveillance of patients with transfusional hemosiderosis treated with deferasirox in actual practice setting

Funding: This study was funded by Novartis Pharma AGObjective:The study evaluates the long-term deferasirox treatment of adult and pediatricpatients with chronic transfusional iron overload in clinical practice.Methods:In this non-interventional study, patients were observed for up to 3 years frominitiation of deferasirox treatment both prospectively and retrospectively for up to 1 yearprior to enrollment. The primary end points were the proportion of patients with≥1 notableincrease in serum creatinine (SCr), and≥1 notable increase in alanine aminotransferase (ALT).Results:Overall, 120 patients were enrolled and 51 completed the study, with a limited 3-yeardropout rate of 12.5% due to adverse events (AEs). Increase in SCr > 33% above baseline and theage-adjusted ULN (upper limit of normal) was observed in 14 patients (95%CI, 7.1-19.2). The ALTlevels >5 × ULN was observed in 1 patient. Most frequent AEs reported during treatment withdeferasirox include gastrointestinal disturbances.Conclusions:The long-term treatment with deferasirox was manageable in most transfusion-dependent patients with no unexpected safetyfindings. Regular monitoring and an adjusteddeferasirox dosing strategy per local labels allowed continued iron chelation treatment andcontrol of transfusional iron in the majority of patients on study

Midostaurin plus daunorubicin or idarubicin for young and older adults with FLT3 -mutated AML : a phase 3b trial

The pivotal RATIFY study demonstrated midostaurin (50 mg twice daily) with standard chemotherapy significantly reduced mortality in adult patients (60 years) patients with FLT3 mut ND-AML. Compared with RATIFY, this study extended midostaurin treatment from 14 days to 21 days, substituted anthracyclines (idarubicin or daunorubicin), and introduced variation in standard combination chemotherapy dosing ("7+3" or "5+2" in more fragile patients). Total 301 patients (47.2% >60 years and 82.7% with FLT3-ITD mut ) of median age 59 years entered induction phase. Overall, 295 patients (98.0%) had at least 1 adverse event (AE), including 254 patients (84.4%) with grade ≥3 AE. The grade ≥3 serious AEs occurred in 134 patients. No difference was seen in AE frequency between age groups, but grade ≥3AE frequency was higher in older patients. Overall, complete remission (CR) rate including incomplete hematologic recovery (CR + CRi) (80.7% [95% confidence interval, 75.74-84.98]) was comparable between age groups (≤60 years [83.5%]; >60 to ≤70 years [82.5%]; in patients >70 years [64.1%]) and the type of anthracycline used in induction. CR + CRi rate was lower in males (76.4%) than females (84.4%). Overall, the safety and efficacy of midostaurin remains consistent with previous findings, regardless of age, sex, or induction regimen. The trial is registered at as #

Midostaurin plus daunorubicin or idarubicin for young and elderly adults with FLT3-mutated AML: a Phase 3b trial

The pivotal RATIFY study demonstrated midostaurin (50 mg b.i.d.) with standard chemotherapy significantly reducing mortality in adult patients (<60 years) with newly diagnosed (ND) FLT3mut acute myeloid leukemia (AML). Considering that AML often present in older patients who show poor response to chemotherapy, this open-label, multicenter Phase 3b trial was designed to further assess safety and efficacy of midostaurin plus chemotherapy in induction, consolidation, and maintenance monotherapy in young (<60 years) and older (>60 years) patients with FLT3mut ND-AML. Compared with RATIFY, this study extended midostaurin treatment from 14 days to 21 days, substituted anthracyclines (idarubicin or daunorubicin), and introduced variation in standard combination chemotherapy dosing ("7+3" or "5+2" in more fragile patients). Total 301 patients (47.2% >60 years, 82.7% with FLT3-ITDmut) of median age 59 years entered induction phase. Overall, 295 patients (98.0%) had at least 1 adverse event (AE), including 254 patients (84.4%) with grade ≥3 AE. The grade ≥3 serious AEs occurred in 134 patients. No difference was seen in AE frequency between age groups, but grade ≥3AE frequency was higher in older patients. 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%]; little less in patients >70 years [64.1%]) and the type of anthracycline used in induction. CR+CRi rate was lower in males (76.4%) than females (84.4%). Overall, safety and efficacy of midostaurin remains consistent with previous findings, regardless of age, gender, or induction regimen. The trial is registered at clinicaltrials.gov: NCT03379727