AML MDS
IMPORTANT SAFETY INFORMATION PRESCRIBING INFORMATION REFERENCES

TIBSOVO IS NONMYELOSUPPRESSIVE,
WITH A WELL-CHARACTERIZED SAFETY PROFILE

Adverse reactions ≥10% in patients with R/R MDS1

The majority of adverse reactions with TIBSOVO were Grades 1 or 21
Serious adverse reactions in ≥5% of patients included differentiation syndrome (11%), fatigue (5%), and rash (5%)1
Differentiation syndrome was resolved in all patients treated with TIBSOVO5
R/R, relapsed or refractory.
Please see Important Safety Information and Full Prescribing Information, including BOXED WARNING for AML and MDS patients.
EFFICACY SAFETY DOSING mIDH1/MOA NCCN
GUIDELINES® MDS & AML SUMMARY

REFERENCES

1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2023.
2. Servier announces FDA approval of TIBSOVO® (ivosidenib tablets) for the treatment of IDH1-mutated relapsed or refractory (R/R) myelodysplastic syndromes (MDS). Servier Pharmaceuticals LLC. 2023. Accessed March 31, 2025. https://servier.us/blog/servier-announces-fda-approval-of-tibsovo-ivosidenib-tablets-for-the-treatment-of-idh1-mutated-relapsed-or-refractory-r-r-myelodysplastic-syndromes-mds/
3. Data on file. Servier Pharmaceuticals LLC.
4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myelodysplastic Syndromes Version 2.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed March 31, 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.
5. DiNardo CD, Roboz GJ, Watts JM, et al. Final phase I substudy results of ivosidenib in patients with mutant IDH1 relapsed/refractory myelodysplastic syndrome. Blood Adv. 2024;8(15):4209-4220. doi:10.1182/bloodadvances.2023012302
6. Platzbecker U, Kubasch AS, Homer-Bouthiette C, Prebet T. Current challenges and unmet medical needs in myelodysplastic syndromes. Leukemia. 2021;35(8):2182-2198. doi:10.1038/s41375-021-01265-7
7. Rodriguez-Sevilla JJ, Adema V, Garcia-Manero G, Colla S. Emerging treatments for myelodysplastic syndromes: biological rationales and clinical translation. Cell Rep Med. 2023;4(2):100940. doi:10.1016/j.xcrm.2023.100940
8. Kubasch AS, Platzbecker U. Setting fire to ESA and EMA resistance: new targeted treatment options in lower risk myelodysplastic syndromes. Int J Mol Sci. 2019;20(16):3853. doi:10.3390/ijms20163853
9. Gangat N, Patnaik MM, Tefferi A. Myelodysplastic syndromes: contemporary review and how we treat. Am J Hematol. 2016;91(1):76-89. doi:10.1002/ajh.24253
10. Balducci L. Transfusion independence in patients with myelodysplastic syndromes: impact on outcomes and quality of life. Cancer. 2006;106(10):2087-2094. doi:10.1002/cncr.21860
11. Germing U, Oliva EN, Hiwase D, Almeida A. Treatment of anemia in transfusion-dependent and non-transfusion-dependent lower-risk MDS: current and emerging strategies. Hemasphere. 2019;3(6):e314 doi:10.1097/HS9.0000000000000314
12. Gangat N, Begna KH, Al-Kali A, et al. Predictors of anemia response to momelotinib therapy in myelofibrosis and impact on survival. Am J Hematol. 2023;98(2):282-289. doi:10.1002/ajh.26778
13. Steensma DP. Myelodysplastic syndromes current treatment algorithm 2018. Blood Cancer J. 2018;8(5):47. doi:10.1038/s41408-018-0085-4
14. Bhatt VR, Steensma DP. Hematopoietic cell transplantation for myelodysplastic syndromes. J Oncol Pract. 2016;12(9):786-792. doi:10.1200/JOP.2016.015214
15. Courville EL, Griffith M, Ustun C, Yohe S, Warlick E. Impending relapse of myelodysplastic syndrome after allogeneic transplant is difficult to diagnose and requires a multi-modal approach. BMC Clin Pathol. 2017;17:28. doi:10.1186/s12907-017-0066-8
16. Nakajima H. Molecular pathogenesis and treatment of myelodysplastic syndromes. Intern Med. 2021;60(1):15-23. doi:10.2169/internalmedicine.4214-19
17. Raineri S, Mellor J. IDH1: linking metabolism and epigenetics. Front Genet. 2018;9:493. doi:10.3389/fgene.2018.00493
18. Thol F, Weissinger EM, Krauter J, et al. IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis. Haematologica. 2010;95(10):1668-1674. doi:10.3324/haematol.2010.025494
19. Jin J, Hu C, Yu M, et al. Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis. PLoS One. 2014;9(6):e100206. doi:10.1371/journal.pone.0100206
20. Komrokji R, Al Ali N, Chan O, et al. IDH mutations are enriched in myelodysplastic syndrome patients with severe neutropenia and can be a potential for targeted therapy. Haematologica. 2023;108(4):1168-1172. doi:10.3324/haematol.2022.281607
21. Guess T, Potts CR, Bhat P, et al. Distinct patterns of clonal evolution drive myelodysplastic syndrome progression to secondary acute myeloid leukemia. Blood Cancer Discov. 2022;3(4):316-329. doi:10.1158/2643-3230.BCD-21-0128
22. DiNardo CD, Jabbour E, Ravandi F, et al. IDH1 and IDH2 mutations in myelodysplastic syndromes and role in disease progression. Leukemia. 2016;30(4):980-984. doi:10.1038/leu.2015.211
23. Molenaar RJ, Wilmink JW. IDH1/2 mutations in cancer stem cells and their implications for differentiation therapy. J Histochem Cytochem. 2022;70(1):83-97. doi:10.1369/00221554211062499
24. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36(7):1703-1719. doi:10.1038/s41375-022-01613-1
25. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140(11):1200-1228. doi:10.1182/blood.2022015850

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

Relapsed or Refractory Myelodysplastic Syndromes (MDS)

For the treatment of adult patients with relapsed or refractory MDS

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN AML AND MDS
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 and MDS: 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, electrolyte abnormalities, or 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
In patients with AML, 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
In patients with MDS, the most common adverse reactions including laboratory abnormalities (≥25%) are creatinine increased, hemoglobin decreased, arthralgia, albumin decreased, aspartate aminotransferase increased, fatigue, diarrhea, cough, sodium decreased, mucositis, decreased appetite, myalgia, phosphate decreased, pruritus, and rash
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 and MDS patients.

Adverse reactions ≥10% in patients with R/R MDS1

R/R, relapsed or refractory.

Select laboratory abnormalities (≥15%) that worsened from baseline in patients with R/R MDS1,a

aLaboratory abnormality is defined as new or worsened by at least one grade from baseline, or if baseline is unknown.1
R/R, relapsed or refractory.

Dose modifications seen with TIBSOVO1

Permanent discontinuation of TIBSOVO due to an adverse reaction occurred in 1 (5%) patient. The adverse reaction that resulted in permanent discontinuation was fatigue
Adverse reactions leading to dose interruption of TIBSOVO occurred in 16% of patients. Adverse reactions that required dose interruption in ≥5% were differentiation syndrome, leukocytosis, and rash
Dose reductions of TIBSOVO due to an adverse reaction occurred in 16% of patients. Adverse reactions that required a dose reduction in ≥5% included differentiation syndrome, fatigue, and rash

Identifying and managing differentiation syndrome1

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
IV, intravenous.