pixel
✕

You are now leaving the
TIBSOVO® healthcare professional website.

Return to TibsovoPro.com ›
Continue

TIBSOVO helps fill an important treatment gap in R/R MDS1,2

First-line therapies for MDS often result in relapse or a lack of response and historically, patients with R/R MDS have had limited therapeutic options3,4

Supportive care agents
  • ESAs and EMAs are used to treat anemia in MDS, but primary resistance to ESA is common, and 70% of patients relapse4
  • ~90% of MDS patients develop chronic anemia and may require long-term transfusion dependence, which can lead to long-term complications such as iron toxicity5-7
HMA therapy
  • Although HMAs are widely used in MDS, patients rarely achieve CR and most experience HMA failure2,8
  • Outcomes for patients after HMA failure are poor, with a median survival of less than 6 months9
HCT
  • HCT is the only curative option for MDS, but only around one-third of higher-risk patients are eligible2,10
  • Relapse occurs in 20% to 50% of patients11

CR, complete remission; EMA, erythroid maturation agent; ESA, erythropoiesis-stimulating agent; HCT, hematopoietic cell transplantation; HMA, hypomethylating agent; R/R, relapsed or refractory.

TIBSOVO is the first and only FDA-approved therapy to target mIDH1 in R/R MDS1,12

IDH1 mutations are considered early drivers in the progression of MDS13,14

IDH1 mutations block normal differentiation of myeloblasts1,15,16

IDH1 Mutations Blocking Differentiation of Myeloblasts
IDH1 Mutations Blocking Differentiation of Myeloblasts
  • IDH1 mutations are recurring molecular abnormalities associated with poor prognosis in both MDS and AML15,17-19
  • Up to 4% of MDS patients harbor IDH1 mutations, and the mutation rate may double in patients who progress to AML2,17
    • Up to 40% of MDS patients progress to AML20
    • Progression to AML occurs more frequently and rapidly in patients with high-risk MDS20
  • mIDH1 MDS is associated with a higher incidence of neutropenia, higher rate of transformation to AML, and poorer overall and leukemia-free survival17,21,22
    • 2-year survival rate for patients with mIDH1 MDS was 14% compared to 52% for patients with wtIDH1 MDS17
    • 67% of patients with mIDH1 MDS transformed to AML compared to 28% of patients with wtIDH1 MDS17

2-HG, 2-hydroxyglutarate; AML, acute myeloid leukemia; HCT, hematopoietic cell transplantation; HMA, hypomethylating agent; IDH1, isocitrate dehydrogenase-1; mIDH1, mutated IDH1; R/R, relapsed or refractory; wtIDH1, wild-type IDH1.

The importance of retesting for IDH1 mutations2

Patients should be retested at the first suspicion of clinical change, as IDH1 mutations can arise anytime during the course of MDS2

  • Initial molecular testing should always be performed at diagnosis, but the molecular profile of patients with MDS can change over time2
  • The number of genetic mutations affects risk stratification of patients with MDS, as a higher number of DNA alterations is associated with worse outcomes23
  • Retest your patients for IDH1 mutations after disease progression or relapse2

IDH1, isocitrate dehydrogenase-1.

Consider TIBSOVO for patients with mIDH1 MDS experiencing their first relapse1

TIBSOVO is a recommended treatment option for MDS24

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommends ivosidenib (TIBSOVO) as a targeted treatment option for certain patients with refractory MDS with IDH1 mutations.9,a

TIBSOVO can be used to treat both lower- and higher-risk MDSb

  • NCCN Guidelines® recommend ivosidenib (TIBSOVO) as an option for certain patients for the management of24:
Lower-risk MDS with
IDH1 mutationsa
Lower risk-MDS with
symptomatic anemia
with IDH1 mutations
Higher-risk MDS with
IDH1 mutationsa
  • NCCN Guidelines recommend genetic testing for somatic mutations (ie, acquired mutations) in genes associated with MDS

aCategory 2A recommendation for lower-risk disease, including for patients with symptomatic anemia, and higher-risk disease. To view the most recent and complete version of the guidelines, visit NCCN.org.

bNCCN guidelines to treat certain patients with MDS is based on risk stratification at diagnosis using IPSS-R.

IDH1, isocitrate dehydrogenase-1; NCCN, National Comprehensive Cancer Network® (NCCN®).

TIBSOVO is the first-in-class differentiation therapy to target mIDH1 in R/R MDS1,12

TIBSOVO restores differentiation of myeloblasts1,25,26

TIBSOVO® Restoring Differentiation of Myeloblasts
TIBSOVO® Restoring Differentiation of Myeloblasts
  • TIBSOVO inhibits mutant IDH1 proteins and subsequently reduces 2-HG levels by >95%, releasing the block on myeloblast differentiation and helping to restore normal cell function25
  • TIBSOVO is a differentiation therapy that includes cellular differentiation; a minimum of 6 months of treatment may be required to see a clinical response1

2-HG, 2-hydroxyglutarate; IDH1, isocitrate dehydrogenase-1; R/R, relapsed or refractory.

Learn about MDS & AML

References: 1. Tibsovo. Package insert. Servier Pharmaceuticals LLC; 2023. 2. 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 3. 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 4. 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 5. 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 6. 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 7. 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 8. Gangat N, Komrokji RS, Tefferi A. Venetoclax and hypomethylating agent therapy in myelodysplastic syndromes: big picture perspective. Am J Hematol. 2023;98(2):225-228. doi:10.1002/ajh.26781 9. Steensma DP. Myelodysplastic syndromes current treatment algorithm 2018. Blood Cancer J. 2018;8(5):47. doi:10.1038/s41408-018-0085-4 10. Bhatt VR, Steensma DP. Hematopoietic cell transplantation for myelodysplastic syndromes. J Oncol Pract. 2016;12(9):786-792. doi:10.1200/jop.2016.015214 11. 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 12. 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. Published October 24, 2023. Accessed March 16, 2024. 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/ 13. 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 14. 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 15. Nakajima H. Molecular pathogenesis and treatment of myelodysplastic syndromes. Intern Med. 2021;60(1):15-23. doi:10.2169/internalmedicine.4214-19 16. Raineri S, Mellor J. IDH1: linking metabolism and epigenetics. Front Genet. 2018;9:493. doi:10.3389/fgene.2018.00493 17. 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 18. Xu Q, Li Y, Lv N, et al. Correlation between isocitrate dehydrogenase gene aberrations and prognosis of patients with acute myeloid leukemia: a systematic review and meta-analysis. Clin Cancer Res. 2017;23(15):4511-4522. doi:10.1158/1078-0432.CCR-16-2628 19. 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 20. Bănescu C, Tripon F, Muntean C. The genetic landscape of myelodysplastic neoplasm progression to acute myeloid leukemia. Int J Mol Sci. 2023;24(6):5734. doi:10.3390/ijms24065734 21. 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 22. 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 23. Bernard E, Tuechler H, Greenberg PL, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evid. 2022;1(7):EVIDoa2200008. doi:10.1056/EVIDoa2200008 24. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myelodysplastic Syndromes V.1.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed February 20, 2024. 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 25. Data on file. Servier Pharmaceuticals LLC. 26. 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

 

Indication

TIBSOVO is indicated for the treatment of adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN 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 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

The most common adverse reactions including laboratory abnormalities (≥25%) in patients with relapsed or refractory MDS 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 MDS patients.

pixel pixel
 

INDICATION

TIBSOVO is indicated for the treatment of adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

Indication & Important Safety Information

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME IN 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.