Gilteritinib (XOSPATA) is the only Category 1 recommendation for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a FLT3 mutation in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia1*†
WARNING: DIFFERENTIATION SYNDROME
Patients treated with XOSPATA have experienced symptoms of differentiation syndrome, which can be fatal or life-threatening if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, or renal dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.
Select Safety Information Contraindication XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials.
See below for additional Important Safety Information.
NCCN Guidelines®recommend retesting for FLT3 mutation each time a patient has a relapse or progression1
This is important because FLT3 mutation status can change over the course
of a patient’s disease1-3
It is estimated that 37% of newly diagnosed patients with AML have FLT3 mutations, making them the most common mutations in AML4
In a retrospective, multicenter study of 138 adult patients with R/R AML treated with intensive salvage chemotherapy regimens, FLT3-ITD mutations were associated with an adverse impact on OS5
XOSPATA sets a standard in R/R FLT3m+ AML1,6
Gilteritinib (XOSPATA) is the ONLY Category 1† recommendation in the NCCN Guidelines® for patients with relapsed or refractory FLT3m+ AML1
XOSPATA—an oral monotherapy FLT3-ITD and -TKD inhibitor—was evaluated in a Phase 3, open-label, multicenter, randomized clinical trial compared with a prespecified salvage chemotherapy‡§||¶ in 371 adult patients with relapsed or refractory FLT3m+ AML6,7
The efficacy of XOSPATA was based on an interim analysis and confirmed in a final analysis6
The final analysis evaluated the endpoint of OS, which was measured from the date of randomization until death by any cause
Randomization was stratified by patient response to first-line AML treatment and prespecified chemotherapy6††
Prespecified chemotherapy regimens included6
High-intensity combination regimens MEC‡ and FLAG-IDA§
Low-intensity regimens LDAC|| and AZA¶
Transplant was allowed in the trial for eligible patients7‡‡
Patients who achieved a response in either treatment arm that allowed them to undergo HSCT based on each institution’s assessment—and who had a donor identified—could receive transplant during the study
*Published 10-14-2020.1 †Category 1: Based on high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.1 ‡MEC: mitoxantrone 8 mg/m2, etoposide 100 mg/m2 and cytarabine 1000 mg/m2 once daily by IV infusion for days 1 to 5.6 §FLAG-IDA: granulocyte colony-stimulating factor 300 mcg/m2 once daily by SC injection days 1 to 5, fludarabine 30 mg/m2 once daily by IV infusion days 2 through 6, cytarabine 2000 mg/m2 once daily by IV infusion days 2 through 6, idarubicin 10 mg/m2 once daily by IV infusion days 2 through 4.6 ||LDAC: cytarabine 20 mg twice daily by SC injection or IV infusion for 10 days.6 ¶AZA: azacitidine 75 mg/m2 once daily by SC injection or IV infusion for 7 days.6 #CR was defined as normal marrow differential with <5% blasts, ANC ≥1.0 × 109/L, platelets ≥100 × 109/L, no evidence of extramedullary leukemia and must have been RBC and platelet transfusion independent.6
**Transfusion independence was defined as patients who were dependent on RBC and/or platelet transfusions at baseline and became independent of RBC and platelet transfusions during any 56-day post-baseline period.6 ††Prior AML chemotherapy regimens included standard-dose cytarabine + idarubicin (39%); high-dose cytarabine (27%); standard-dose cytarabine + daunorubicin (26%); azacitidine (7%); decitabine (5%); high-dose cytarabine + daunorubicin (4%); low-dose cytarabine (4%); high-dose cytarabine + idarubicin (3%); standard-dose cytarabine + mitoxantrone (3%) and standard-dose cytarabine+ daunorubicin + cladribine (1%); as well as other regimens (44%).7 ‡‡Treatment with XOSPATA was stopped prior to starting the condition regimen for HSCT.7 XOSPATA treatment could be resumed after transplant in patients who were between 30 and 90 days post–HSCT, had successful engraftment with ANC ≥500/mm3 and platelets ≥20,000/mm3 without transfusions, did not have Grade ≥2 acute GVHD, and were in CRc.
Important Safety Information continued Warnings and Precautions Differentiation Syndrome (See BOXED WARNING)3% of 319 patients treated with XOSPATA in the clinical trials experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms of differentiation syndrome in patients treated with XOSPATA included fever, dyspnea, pleural effusion, pericardial effusion, pulmonary edema, hypotension, rapid weight gain, peripheral edema, rash, and renal dysfunction. Some cases had concomitant acute febrile neutrophilic dermatosis. Differentiation syndrome occurred as early as 2 days and up to 75 days after XOSPATA initiation and has been observed with or without concomitant leukocytosis. If differentiation syndrome is suspected, initiate
dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. Taper corticosteroids after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt XOSPATA until signs and symptoms are no longer severe.
Posterior Reversible Encephalopathy Syndrome (PRES)1% of 319 patients treated with XOSPATA in the clinical trials experienced posterior reversible encephalopathy syndrome (PRES) with symptoms including seizure and altered mental status. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinue XOSPATA in patients who develop PRES.
Prolonged QT IntervalXOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). 1% of the 317 patients with a post-baseline QTc measurement on treatment with XOSPATA in the clinical trial were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration.
Pancreatitis4% of 319 patients treated with XOSPATA in the clinical trials experienced pancreatitis. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis.
Embryo-Fetal ToxicityXOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus.
Adverse Reactions Fatal adverse reactions occurred in 2% of patients receiving XOSPATA. These were cardiac arrest (1%) and one case each of differentiation syndrome and pancreatitis. The most frequent (≥5%) nonhematological serious adverse reactions reported in patients were fever (13%), dyspnea (9%), renal impairment (8%), transaminase increased (6%) and noninfectious diarrhea (5%).
7% discontinued XOSPATA treatment permanently due to an adverse reaction. The most common (>1%) adverse reactions leading to discontinuation were aspartate aminotransferase increased (2%) and alanine aminotransferase increased (2%).
The most frequent (≥5%) grade ≥3 nonhematological adverse reactions reported in patients were transaminase increased (21%), dyspnea (12%), hypotension (7%), mucositis (7%), myalgia/arthralgia (7%), and fatigue/malaise (6%).
Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT prolonged (9%), hypersensitivity (8%), pancreatitis (5%), cardiac failure (4%), pericardial effusion (4%), acute febrile neutrophilic dermatosis (3%), differentiation syndrome (3%), pericarditis/myocarditis (2%), large intestine perforation (1%), and posterior reversible encephalopathy syndrome (1%).
Drug Interactions Combined P-gp and Strong CYP3A InducersConcomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure which may decrease XOSPATA efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers.
Strong CYP3A inhibitorsConcomitant use of XOSPATA with a strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity.
Drugs that Target 5HT2B Receptor or Sigma Nonspecific ReceptorConcomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient.
Specific Populations LactationAdvise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.
Click herefor Full Prescribing Information, including BOXED WARNING for additional safety information.
Please see our required disclosures for healthcare providers inVermontand Colorado.
This email was sent to firstname.lastname@example.org because you have an account with or are a valued partner of ION Solutions. If you no longer wish to receive these types of emails, please click here to unsubscribe or update your email preferences.