Improving Outcomes for AML Patients with Genetic Testing and Targeted Therapy

Sponsored by Servier U.S.

When I began practicing medicine as a hematologist, treatment options for patients with acute myeloid leukemia (AML) were limited to just a few types of chemotherapy. Although there are many different subtypes of AML with different prognoses, the treatment regimen remained the same for all patients. My colleagues and I were unable to tailor treatment approaches to individual patients due to limited therapeutic options.

Over the past decade, I have seen a profound shift in our ability to treat people with AML. We now have access to cutting-edge technologies and innovative methods for patient evaluation, including genetic and biomarker testing, that provide a deeper understanding of a patient’s unique disease characteristics. These developments have helped usher in a new era of targeted, personalized AML treatment options that can target specific mutations and biomarkers and help improve patient outcomes.

Patients can only benefit from a targeted therapy if appropriate testing is done to identify specific genetic mutations and then select the most appropriate therapy. AML treatment is not “one-size-fits all,” and it is crucial that genetic testing for specific mutations be included in a patient’s overall treatment plan.

Focus on IDH1 Mutations in AML

In AML, heterozygous missense mutations in isocitrate dehydrogenase (IDH) genes are present.¹ IDH1 mutations prevent blood stem cells from differentiating and can lead to proliferation of leukemic cells.²

The presence of IDH1 mutations, which are found in 6-10% of patients with AML, often leads to a poor prognosis, including shorter overall survival rates.^3,4,5 Mutant IDH1 catalyzes the production of D-2-hydroxglutarate, leading to disruption in cellular metabolism and epigenetic regulation and contributing to oncogenesis.⁶

It’s critical for patients to be tested for the presence of mutations so their physicians can select a treatment regimen that addresses the underlying biology of their disease.

Treating AML Through Targeted IDH1 Inhibition

While working as a clinician, I saw first-hand the urgent need for effective targeted therapies for patients with AML. Eventually, I decided to leave academic medicine and join the pharmaceutical industry to focus on oncology drug development to address these unmet needs.

I joined Servier to oversee the pivotal Phase 3 AGILE clinical trial evaluating TIBSOVO® (ivosidenib tablets) plus azacitidine in patients with IDH1-mutated AML.⁷ The AGILE trial was the only Phase 3 trial designed specifically for newly diagnosed patients with IDH1-mutated AML who are ineligible for intensive chemotherapy.

A first-in-class oral medicine, TIBSOVO targets and inhibits the mutant IDH1 enzyme, which can help myeloblasts grow into healthy blood cells.

See below for Important Safety Information, including the risk of Differentiation Syndrome in AML patients. Click here for Prescribing Information.

The U.S. FDA approval of TIBSOVO in May 2022 was supported by data from the global, multicenter, double-blind, randomized, placebo-controlled AGILE trial, evaluating the efficacy and safety of TIBSOVO in combination with azacitidine versus placebo plus azacitidine in adults with newly diagnosed IDH1-mutated AML who were unfit to receive intensive chemotherapy because of older age or comorbidities.⁷

Results were published in the New England Journal of Medicine and demonstrated a statistically significant improvement in event-free survival (EFS) and overall survival (OS).³ Patients treated with TIBSOVO plus azacitidine experienced a threefold improvement in median OS.³

The most common serious adverse reactions in patients who received TIBSOVO in combination with azacitidine included differentiation syndrome. Adverse reactions leading to discontinuation or dose disruption were differentiation syndrome, pulmonary embolism, neutropenia, electrocardiogram QT prolonged, and thrombocytopenia. ³

A post-hoc analysis of long-term follow-up data from the AGILE trial, which was published in Blood Advances in October 2025, confirmed the findings from the primary analysis.⁵ Results showed a sustained survival benefit and longer median OS with TIBSOVO plus azacitadine, and improved hematologic recovery.⁵ No new or unexpected safety signals were observed.⁵ 

These findings support the use of TIBSOVO plus azacitidine as a standard of care in the frontline treatment of patients with IDH1-mutated AML who are ineligible for intensive chemotherapy.⁵

With the availability of TIBSOVO, patients with IDH1-mutated AML have access to a medicine that was specifically designed to target IDH-1 mutations. Physicians should be aware of the safety profile of TIBSOVO before prescribing, including the potential risk of differentiation syndrome, which is described in more detail below.

Improving Outcomes in AML With Genetic Testing

Precision medicine has come a long way over the past decade. Today, there are multiple targeted therapies available for patients – including TIBSOVO – that can help improve patient outcomes.

Targeted oncology therapies like TIBSOVO can only benefit patients if their physicians are aware of the presence of these mutations and have the information they need to inform treatment selection. Genetic testing should be a priority for all patients with AML to ensure patients and their care teams fully understand the unique characteristics of their disease and are aware of the presence of mutations. This information is critical to guiding informed treatment decisions and disease management throughout the treatment journey, and can help make sure patients are receiving the most appropriate treatment regimen.

As science evolves, our approach to treating patients must evolve with it.

For more information, please visit www.TIBSOVOpro.com.

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 the use of intensive induction chemotherapy

Relapsed or Refractory AML

• For the treatment of adult patients with relapsed or refractory AML

IMPORTANT SAFETY INFORMATION

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 (e.g., 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

• 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.

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.

References

1. Issa GC., DiNardo CD. (2021) Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm. Blood Cancer J. https://doi.org/10.1038/s41408-021-00497-1 Accessed November 2025.
2. Grisham J. Research clarifies how IDH mutations cause cancer. Memorial Sloan Kettering Cancer Center. In the news. https://www.mskcc.org/news/research-clarifies-how-idh-mutations-cause. Accessed November 2025.
3. Montesinos, P., Recher, C., Vives S., et al. (2022) Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2117344. Accessed November 2025.
4. Thol F., Weissinger EM., Krauter J., et al. (2010) IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis. Haematologica. https://doi.org/10.3324/haematol.2010.025494. Accessed November 2025.
5. Montesinos P., Marchione, D., Recher, C., et al. (2025) Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML. Blood Advances. https://doi.org/10.1182/bloodadvances.2025016399. Accessed November 2025.
6. Ward, P. S., Patel, J., Wise, D. R., et al. (2010). The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer cell, 17(3), 225–234. https://doi.org/10.1016/j.ccr.2010.01.020.
7. U.S. National Library of Medicine. (2017). Study of AG-120 (ivosidenib) versus placebo in combination with azacitidine in patients with previously untreated IDH1 mutant acute myeloid leukemia (AGILE) (ClinicalTrials.gov Identifier No. NCT03173248). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT03173248.

US-03860 12/25