Gilteritinib (XOSPATA) is the ONLY Category 1 recommendation for patients with relapsed or refractory AML with a FLT3 mutation in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)1

FLT3 Mutation Testing at Relapse or Progression Can Inform Your Treatment Decisions1

FLT3 mutation status can change over the course of AML treatment2

The development of FLT3-ITD mutations has been strongly correlated with disease progression and worse prognosis.3

10%

In a retrospective study of 324 patients with AML, a new FLT3-ITD mutation was identified at time of relapse in 10% of the 77 patients who were FLT3-ITD negative at initial diagnosis and subsequently experienced relapse.2

25%

In another retrospective analysis of patients with FLT3m+ AML, among patients with a FLT3-ITD mutation alone who were treated with a FLT3 inhibitor (n=60), 25% (n=15) had both FLT3-ITD and -TKD mutations at the end of treatment.4

A PCR* Test SUCH AS LEUKOSTRAT® CDx FLT3 MUTATION ASSAY is an Effective Way to Identify FLT3 Mutations5

PCR tests have a turnaround time of 2 to 3 business days.5

PCR is a diagnostic tool that may be used to identify FLT3 mutations in AML
PCR*
Turnaround time5
2-3 business days
Can detect FLT3-ITD 5 Yes
Can detect FLT3-TKD 5 Yes
Can detect emergence of new mutations at relapse3 Yes

*LeukoStrat CDx FLT3 Mutation Assay is the only FDA-approved test for FLT3 mutations and the only approved companion diagnostic to XOSPATA.5,7

Due to poor outcomes associated with FLT3-ITD mutations in AML, confirming FLT3 mutation status at relapse or progression can inform a targeted treatment strategy1-3,8

Learn About XOSPATA for Relapsed
or Refractory FLT3m+ AML

AML=acute myeloid leukemia; CDx=companion diagnostic; FDA=Food and Drug Administration; FLT3=FMS-like tyrosine kinase 3; ITD=internal tandem duplication; m+=mutation-positive; PCR=polymerase chain reaction; TKD=tyrosine kinase domain.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.1.2022. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed 12-03-2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Nazha A, Cortes J, Faderl S, et al. Activating internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD) at complete response and relapse in patients with acute myeloid leukemia. Haematologica 2012;97(8):1242-5. 3. Warren M, Luthra R, Yin CC, et al. Clinical impact of change of FLT3 mutation status in acute myeloid leukemia patients. Mod Pathol 2012;25(10):1405-12. 4. Alvarado Y, Kantarjian HM, Luthra R, et al. Treatment with FLT3 inhibitor in patients with FLT3-mutated acute myeloid leukemia is associated with development of secondary FLT3-tyrosine kinase domain mutations. Cancer 2014;120(14):2142-9. 5. Invivoscribe. LeukoStrat® CDx FLT3 mutation assay. https://www.invivoscribe.com/clinical-services/leukostrat-cdx-flt3-mutation-assay. Accessed 10-21-2021. 6. Patnaik MM. The importance of FLT3 mutational analysis in acute myeloid leukemia. Leuk Lymphoma 2018;59(10):2273-86. 7. US Food and Drug Administration. List of cleared or approved companion diagnostic devices (in vitro and imaging tools) (10-25-2021). https://www.fda.gov/media/119249/download. Accessed 10-30-2021. 8. McCormick SR, McCormick MJ, Grutkoski PS, et al. FLT3 mutations at diagnosis and relapse in acute myeloid leukemia: cytogenetic and pathologic correlations, including cuplike blast morphology. Arch Pathol Lab Med 2010;134(8):1143-51.

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.

Important Safety Information

Contraindications

XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials.

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 and other clinical findings 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 1 day and up to 82 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 Interval XOSPATA 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.

Pancreatitis 4% 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 Toxicity XOSPATA 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 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 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%).

Lab Abnormalities Shifts to grades 3-4 nonhematologic laboratory abnormalities in XOSPATA treated patients included phosphate decreased (14%), alanine aminotransferase increased (13%), sodium decreased (12%), aspartate aminotransferase increased (10%), calcium decreased (6%), creatine kinase increased (6%), triglycerides increased (6%), creatinine increased (3%), and alkaline phosphatase increased (2%).

Drug Interactions

Combined P-gp and Strong CYP3A Inducers Concomitant 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 inhibitors Concomitant 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 Receptor Concomitant 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.

P-gp, BCRP, and OCT1 Substrates Based on in vitro data, gilteritinib is a P-gp, breast cancer resistant protein (BCRP), and organic cation transporter 1 (OCT1) inhibitor. Coadministration of gilteritinib may increase the exposure of P-gp, BCRP, and OCT1 substrates, which may increase the incidence and severity of adverse reactions of these substrates. For P-gp, BCRP, or OCT1 substrates where small concentration changes may lead to serious adverse reactions, decrease the dose or modify the dosing frequency of such substrate and monitor for adverse reactions as recommended in the respective prescribing information.

Specific Populations

Lactation Advise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.

Please see Full Prescribing Information including BOXED WARNING for additional safety information.