Frequently asked questions (FAQs) about TIBSOVO® in AML

TIBSOVO is a treatment option for acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 mutation. TIBSOVO is indicated in combination with azacitidine or as monotherapy for adults with newly diagnosed AML who are 75 years or older or adults who are not eligible for induction chemotherapy, and as monotherapy for adults with relapsed or refractory AML. TIBSOVO + azacitidine is proven to significantly increase overall survival (OS), with 24.0 months median OS (95% CI, 11.3-34.1) vs 7.9 months with AZA (95% CI, 4.1-11.3) in the primary OS analysis and 29.3 months median OS (95% CI, 13.2-NR) vs 7.9 months with AZA (95% CI, 4.1-11.3) in the long-term follow-up analysis.

TIBSOVO is only indicated for patients with a susceptible isocitrate dehydrogenase-1 mutation as detected by an FDA-approved test. TIBSOVO is indicated in combination with azacitidine or as monotherapy for adults with newly diagnosed AML 75 and older or who are not eligible for induction chemotherapy, and as monotherapy for adults with relapsed or refractory AML.

The NCCN Clinical Practice Guidelines in Oncology recommends ivosidenib (TIBSOVO) + azacitidine as a category 1 preferred treatment option for newly diagnosed patients with mutated isocitrate dehydrogenase-1 who are not candidates for intensive remission induction therapy.

TIBSOVO + azacitidine was studied in AGILE, a global, phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Efficacy was established on the basis of event-free survival, overall survival (OS) and rate and duration of complete remission. TIBSOVO + azacitidine significantly increased OS with 24.0 months median OS (95% CI, 11.3-34.1) in the primary OS analysis and 29.3 months median OS (95% CI, 13.2-NR) in the long-term follow-up analysis.

TIBSOVO was studied as a single agent in both the newly diagnosed and relapsed or refractory (R/R) acute myeloid leukemia settings. The pivotal trial for TIBSOVO monotherapy was an open-label, single-arm, multicenter trial. Efficacy was established on the rate of complete remission (CR) and/or CR with partial hematologic recovery (CRh), duration of CR+CRh, as well as the rate of conversion from transfusion dependence to transfusion independence. Of newly diagnosed patients, 43% of newly diagnosed patients achieved CR or CRh (95% CI, 24.5-62.8) and 33% of R/R patients achieved CR or CRh with TIBSOVO (95% CI, 25.8-40.3).

We do have long-term overall survival data for TIBSOVO + azacitidine. TIBSOVO + azacitidine is proven to significantly increase overall survival (OS), with 24.0 months median OS (95% CI, 11.3-34.1) in the primary OS analysis and 29.3 months median OS (95% CI, 13.2-NR) in the long-term follow-up analysis.

TIBSOVO + azacitidine demonstrated significantly higher rates of complete remission (CR) and CR+CR with partial hematologic recovery (CR+CRh) with azacitidine. TIBSOVO + azacitidine demonstrated 51% CR+CRh (95% CI, 39-63) vs 18% CR+CRh with azacitidine (95% CI, 10-28). Median duration of CR was not estimable (NE) as of the data cutoff in the TIBSOVO + azacitidine arm (95% CI, 13.0-NE) and was 11.2 months in the azacitidine arm (95% CI, 3.2-NE).

TIBSOVO was studied as a single agent in both the newly diagnosed and relapsed or refractory (R/R) acute myeloid leukemia settings. The pivotal trial for TIBSOVO monotherapy was an open-label, single-arm, multicenter trial. Efficacy was established on the rate of complete remission (CR) and/or CR with partial hematologic recovery (CRh), duration of CR+CRh, as well as the rate of conversion from transfusion dependence to transfusion independence. 43% of newly diagnosed patients achieved CR or CRh (95% CI, 24.5-62.8) and 33% of R/R patients achieved CR or CRh with TIBSOVO (95% CI, 25.8-40.3).

TIBSOVO (ivosidenib tablets) has a well-characterized safety profile studied in more than 270 patients with mutated isocitrate dehydrogenase-1 acute myeloid leukemia (AML). The most common adverse reactions (≥10%) in patients with AML who received TIBSOVO + azacitidine with difference of ≥2% between arms compared with placebo + azacitidine were nausea, vomiting, electrocardiogram QT prolonged, differentiation syndrome, insomnia, hematoma, leukocytosis, hypertension, arthralgia, dyspnea, and headache.

Adverse reactions ≥10% (any grade) or ≥5% (Grade ≥3) reported in newly diagnosed patients who received TIBSOVO included diarrhea, fatigue, nausea, edema, decreased appetite, leukocytosis, differentiation syndrome, arthralgia, abdominal pain, dyspnea, electrocardiogram QT prolonged, myalgia, constipation, vomiting, mucositis, dizziness, pruritus, rash, cough, neuropathy, dyspepsia, weight decreased, and headache. Adverse reactions ≥10% (any grade) or ≥5% (Grade ≥3) reported in relapsed or refractory patients who received TIBSOVO monotherapy included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, electrocardiogram QT prolonged, rash, pyrexia, cough, constipation, differentiation syndrome, myalgia, vomiting, decreased appetite, chest pain, abdominal pain, headache, pleural effusion, neuropathy, hypotension, and tumor lysis syndrome. Refer to the TIBSOVO (ivosidenib) PI for more information on side effects.

Patients treated with TIBSOVO can develop differentiation syndrome, QTc interval prolongation, and Guillain-Barré syndrome. Proper guidance as outlined in Warnings and Precautions should be followed if patients develop signs or symptoms of a serious adverse reaction. Refer to the TIBSOVO (ivosidenib) PI for more information on side effects.

Patients treated with TIBSOVO can develop differentiation syndrome. 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. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated.

Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

Guillain-Barré syndrome can develop in patients treated with TIBSOVO. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

Refer to the TIBSOVO (ivosidenib) PI for more information on managing serious side effects.

The rate of discontinuation due to adverse events in patients treated with TIBSOVO + azacitidine was comparable to that of placebo + azacitidine (26.8% vs 26.0%). Adverse reactions leading to permanent discontinuation of TIBSOVO in ≥2% of patients were differentiation syndrome (3%) and pulmonary embolism (3%). The most common (>5%) adverse reactions leading to dose interruption of TIBSOVO were neutropenia (25%), electrocardiogram QT prolonged (7%), and thrombocytopenia (7%). Adverse reactions leading to dose reduction of TIBSOVO included electrocardiogram QT prolonged (8%), neutropenia (8%), and thrombocytopenia (1%).

In the trial that studied TIBSOVO monotherapy in the newly diagnosed setting, adverse reactions leading to discontinuation of TIBSOVO were diarrhea (4%) and PRES (4%). The most common (≥10%) adverse reactions leading to dose interruption of TIBSOVO were electrocardiogram QT prolonged (14%) and differentiation syndrome (11%). Adverse reaction leading to dose reduction of TIBSOVO was electrocardiogram QT prolonged (7%).

In the trial that studied TIBSOVO in the relapsed or refractory setting, adverse reactions leading to discontinuation of TIBSOVO were Guillain-Barré syndrome (1%), rash (1%), stomatitis (1%), and creatinine increased (1%). The most common adverse reactions leading to dose interruption of TIBSOVO were electrocardiogram QT prolonged (7%), differentiation syndrome (3%), leukocytosis (3%), and dyspnea (3%). Adverse reactions leading to dose reduction of TIBSOVO included electrocardiogram QT prolonged (1%), diarrhea (1%), nausea (1%), decreased hemoglobin (1%), and increased transaminases (1%).

The recommended dose of TIBSOVO is 500 mg taken orally once daily, until disease progression or unacceptable toxicity. No dose titration is required at treatment initiation. Start TIBSOVO administration on Cycle 1 Day 1 in combination with azacitidine 75 mg/m² subcutaneously or intravenously once daily on Days 1-7 (or Days 1-5 and 8-9) of each 28-day cycle.

The recommended dose for TIBSOVO is 500 mg taken orally, once daily, until disease progression or unacceptable toxicity. TIBSOVO is supplied in two, 250-mg film-coated tablets.

TIBSOVO can be taken with or without food, but should not be administered with a high-fat meal. TIBSOVO tablets should not be split, crushed, or chewed. TIBSOVO should be administered orally about the same time each day. If a dose of TIBSOVO is vomited, a replacement dose should not be administered; patients should wait until the next scheduled dose is due.

If a dose is missed or not taken at the usual time, patients should take the missed dose as soon as possible and at least 12 hours prior to the next scheduled dose. They should return to the normal schedule the following day. They should not take 2 doses within 12 hours. If a dose is vomited, patients should not take a replacement dose; they should wait until the next scheduled dose is due.

Prior to initiating treatment with TIBSOVO, obtain an electrocardiogram (ECG). Monitor ECGs at least once weekly for the first 3 weeks of therapy and then at least once monthly for the duration of therapy. Manage any abnormalities promptly. Assess blood counts and blood chemistries prior to the initiation of TIBSOVO, at least once weekly for the first month, once every other week for the second month, and once monthly for the duration of therapy. Monitor blood creatine phosphokinase weekly for the first month of therapy.

IDH1 mutations are driver mutations that occur in up to 6%-16% of patients with AML. Several studies suggested that mutated IDH1 AML is associated with a poor prognosis. Waiting for genetic and laboratory test results prior to initiating treatment can ensure that patients are given the best treatment option.

Patients with AML should be tested at diagnosis for IDH1 mutations. Waiting for genetic and laboratory test results prior to initiating treatment can ensure that patients are given the best treatment option. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend repeating molecular testing at each relapse or progression.

IDH1 mutations are considered driver mutations in AML and are associated with a poor prognosis. In newly diagnosed AML patients, evidence shows that time from diagnosis to treatment does not affect long-term survival. Waiting for genetic and laboratory test results prior to initiating treatment may ensure that patients are given the best treatment option.

In acute myeloid leukemia (AML), molecular profiling is frequently performed using bone marrow or peripheral blood samples. Polymerase chain reaction (PCR)-based single-gene tests identify genetic mutations such as IDH1. PCR tests are more sensitive, have higher resolution, a more rapid turnaround time, and are associated with lower costs. Next generation sequencing (NGS) allows for parallel sequencing of multiple genes in a single test. In recent years, the use of unique molecular identification in NGS has led to improved sensitivity with reduced sequencing error and noise background. However, turnaround time for NGS is still slower compared with single-gene tests such as PCR.

TIBSOVO targets the mutant isocitrate dehydrogenase-1 (IDH1) enzyme 2-HG to restore myeloid differentiation. In blood samples from patients with AML with mutated IDH1, TIBSOVO decreased 2-HG levels ex vivo, reduced blast counts, and increased percentages of mature myeloid cells.

Resources such as the TIBSOVO + Azacitidine Brochure, the TIBSOVO Dosing Guide, and the TIBSOVO + Azacitidine Long-term Data Brochure are available to download for healthcare professionals.

Resources such as the TIBSOVO Patient Brochure for AML, the Differentiation Syndrome Reference Card, and the TIBSOVO Medication Guide are available. These resources may be useful to patients and caregivers throughout treatment for AML with TIBSOVO.

ServierONE is the Servier Patient Services program. ServierONE Patient Support Services for TIBSOVO offers support with insurance coverage and reimbursement, financial assistance to help patients pay for TIBSOVO, and prescription fulfillment through our network of specialty pharmacies and distributors. For more information visit ServierONE.com or call 1-800-813-5905.

TIBSOVO is only available through our specialty distributors and network specialty pharmacies. TIBSOVO is available through specialty distributors for shipment directly to office- or hospital-based pharmacies and can also ship directly from the specialty pharmacy to your patient’s home or preferred location.

A registration form is available on our website to schedule a visit with a TIBSOVO representative. After you have submitted this registration form, a TIBSOVO sales representative will contact you to schedule your appointment.