AML MDS
IMPORTANT SAFETY INFORMATION PRESCRIBING INFORMATION REFERENCES

In IC-ineligible patients with newly diagnosed AML TIBSOVO HAS A WELL-CHARACTERIZED
SAFETY PROFILE

Adverse reactions (≥10%) in patients with AML who received TIBSOVO + AZA with a difference of ≥2%
between arms compared with PBO + AZA1

TIBSOVO + AZA was associated with a lower rate of infection of any grade compared with PBO + AZA (28% vs 49%)4
TIBSOVO + AZA was associated with fewer severe cytopenias compared with PBO + AZA1,4
aDifferentiation syndrome can be associated with other commonly reported events such as peripheral edema, leukocytosis, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonia, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased.1
AZA, azacitidine; ECG, electrocardiogram; IC, induction chemotherapy; PBO, placebo.
Please see Important Safety Information and Full Prescribing Information, including BOXED WARNING for AML patients.
OVERALL
SURVIVAL
REMISSION
HEMATOLOGIC
RECOVERY
TRANSFUSION
INDEPENDENCE
EFS
RWE
SAFETY
TIBSOVO + AZA
NEWLY DIAGNOSED MONOTHERAPY
NEWLY DIAGNOSED RELAPSED/
REFRACTORY DOSING mIDH1 / MOA GUIDELINES SUMMARY

Adverse reactions (≥10%) in patients with AML who received TIBSOVO + AZA with a
difference of ≥2% between arms compared with PBO + AZA1

TIBSOVO + AZA was associated with a lower rate of infection of any grade compared with PBO + AZA (28% vs 49%)4

aDifferentiation syndrome can be associated with other commonly reported events such as peripheral edema, leukocytosis, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonia, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased.1
AZA, azacitidine; ECG, electrocardiogram; PBO, placebo.

Select laboratory abnormalities (≥10%) that worsened from baseline in patients with newly diagnosed AML who received TIBSOVO + AZA1,a,b

TIBSOVO + AZA was associated with fewer severe cytopenias compared with PBO + AZA1,4

aLaboratory abnormality was defined as new or worsened by at least one grade from baseline or if baseline was unknown.1
bThe denominator used to calculate percentages was the number of treated patients who could be evaluated for Common Terminology Criteria for Adverse Events (CTCAE) for each parameter in each arm.1
AZA, azacitidine; PBO, placebo.

Dose modifications seen with TIBSOVO + AZA

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

REFERENCES

1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2023.
2. de Botton S, Montesinos P, Vives Polo S, et al. Updated efficacy and safety data from the AGILE study in patients with newly-diagnosed acute myeloid leukemia treated with ivosidenib + azacitidine compared to placebo + azacitidine. Poster presented at: 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, IL.
3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia Version 2.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed March 12, 2025. 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.
4. Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med. 2022;386(16):1519-1531. doi:10.1056/NEJMoa2117344
5. Data on file. Servier Pharmaceuticals LLC.
6. Fathi AT, Douglas Smith B, Angiolillo A, et al. Time to resolution of myelosuppression and associated hospitalization in patients with newly diagnosed acute myeloid leukemia treated with ivosidenib+azacitidine compared with azacitidine+placebo. Poster presented at: Eleventh Annual Meeting of the Society of Hematologic Oncology (SOHO 2023); September 6-9, 2023; Houston, TX. Poster AML-446.
7. Smith BD, Lachowiez CA, Ambinder AJ, et al. A comparison of acute myeloid leukemia (AML) regimens: hypomethylating agents combined with ivosidenib or venetoclax in newly diagnosed patients with IDH1 mutations: a real-world evidence study. Poster presented at: 65th Congress of the American Society of Hematology (ASH) Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA.
8. Roboz GJ, DiNardo CD, Stein EM, et al. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood. 2020;135(7):463-471. doi:10.1182/blood.2019002140
9. DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378(25):2386-2398. doi:10.1056/NEJMoa1716984
10. Molenaar RJ, Maciejewski JP, Wilmink JW, van Noorden CJF. Wild-type and mutated IDH1/2 enzymes and therapy responses. Oncogene. 2018;37(15):1949-1960. doi:10.1038/s41388-017-0077-z
11. Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553-567. doi:10.1016/j.ccr.2010.11.015
12. DiNardo CD, Ravandi F, Agresta S, et al. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. Am J Hematol. 2015;90(8):732-736. doi:10.1002/ajh.24072
13. Xu Q, Li Y, Lv N, et al. Correlation between isocitrate dehydrogenase gene aberrations and prognosis of patients with acute myeloid leukemia: a systemic review and meta-analysis. Clin Cancer Res. 2017;23(15):4511-4522. doi:10.1158/1078-0432.CCR-16-2628
14. Bataller A, Kantarjian H, Bazinet A, et al. Outcomes and genetic dynamics of acute myeloid leukemia at first relapse. Haematologica. 2024;109(11):3543-3556. doi:10.3324/haematol.2024.285057
15. Arber DA, Borowitz MJ, Cessna M, et al. Initial diagnostic workup of acute leukemia: Guideline from the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017;141(10):1342-1393. doi:10.5858/arpa.2016-0504-CP
16. Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377. doi:10.1182/blood.2022016867
17. Baden D, Zukunft S, Hernandez G, et al. Time from diagnosis to treatment has no impact on survival in newly diagnosed acute myeloid leukemia treated with venetoclax-based regimens. Haematologica. 2024;109(8):2469-2477. doi:10.3324/haematol.2024.285225
18. Röllig C, Kramer M, Schliemann C, et al. Does time from diagnosis to treatment affect the prognosis of patients with newly diagnosed acute myeloid leukemia? Blood. 2020;136(7):823-830. doi:10.1182/blood.2019004583
19. Döhner H, DiNardo CD, Wei AH, et al. Genetic risk classification for adults with AML receiving less-intensive therapies: the 2024 ELN recommendations. Blood. 2024;144(21):2169-2173. doi:10.1182/blood.2024025409

INDICATIONS &
IMPORTANT SAFETY INFORMATION

INDICATIONS

TIBSOVO is indicated for patients with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test with:

Newly Diagnosed Acute Myeloid Leukemia (AML)

In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy

Relapsed or Refractory AML

For the treatment of adult patients with relapsed or refractory AML

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN AML
Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
WARNINGS AND PRECAUTIONS

Differentiation Syndrome in AML: Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome and creatinine increased.

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. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.

QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (eg, anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.

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: Guillain-Barré syndrome can develop in patients treated with TIBSOVO. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

ADVERSE REACTIONS

The most common adverse reactions including laboratory abnormalities (≥25%) are leukocytes decreased, diarrhea, hemoglobin decreased, platelets decreased, glucose increased, fatigue, alkaline phosphatase increased, edema, potassium decreased, nausea, vomiting, phosphate decreased, decreased appetite, sodium decreased, leukocytosis, magnesium decreased, aspartate aminotransferase increased, arthralgia, dyspnea, uric acid increased, abdominal pain, creatinine increased, mucositis, rash, electrocardiogram QT prolonged, differentiation syndrome, calcium decreased, neutrophils decreased, and myalgia.

DRUG INTERACTIONS

Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.

Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.

Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.

QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.

LACTATION

Advise women not to breastfeed.

Please see Full Prescribing Information, including BOXED WARNING for AML patients.