TIBSOVO® safety profile in R/R mIDH1 MDS

TIBSOVO is nonmyelosuppressive, with a well-characterized safety profile^1,2

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

	TIBSOVO (500 mg daily) (N=19)
Body system Adverse reaction	All grades	Grade 3 or 4
Musculoskeletal and connective tissue disorders
Arthralgiaa	42%	16%
Myalgiab	26%	0
General disorders and administration site conditions
Fatiguec	37%	11%
Respiratory, thoracic, and mediastinal disorders
Cough	32%	0
Dyspnead	21%	0
Gastrointestinal disorders
Diarrhea	32%	0
Mucositise	26%	5%
Constipation	16%	0
Nausea	16%	0
Metabolism and nutrition disorders
Decreased appetite	26%	0
Skin and subcutaneous tissue disorders
Pruritus	26%	0
Rashf	26%	0
Blood system and lymphatic system disorders
Leukocytosisg	16%	5%
Differentiation syndrome	11%	0
Nervous system disorders
Headache	16%	0
Vascular disorders
Hypertension	16%	16%
Investigations
Electrocardiogram QT prolonged	11%	0

^aGrouped term includes arthralgia, back pain, pain in extremity, flank pain, joint swelling, and neck pain.

^bGrouped term includes myalgia, muscle spasms, muscle discomfort, and musculoskeletal chest pain.

^cGrouped term includes fatigue and asthenia.

^dGrouped term includes dyspnea and dyspnea exertional.

^eGrouped term includes oropharyngeal pain, gingivitis, mouth ulceration, stomatitis.

^fGrouped term includes rash, catheter site erythema, and urticaria.

^gGrouped term includes leukocytosis, hyperleukocytosis, and white blood cell count increased.

• 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 TIBSOVO²

mIDH1, mutated IDH1; QTc, corrected QT interval; R/R, relapsed or refractory.

Laboratory abnormalities¹

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

	TIBSOVO (500 mg daily) (N=19)
Parameter	All grades	Grade 3 or 4
Creatinine increased	95%	5%
Hemoglobin decreased	42%	32%
Albumin decreased	37%	0
Aspartate aminotransferase increased	37%	5%
Sodium decreased	32%	5%
Phosphate decreased	26%	5%
Alanine aminotransferase increased	21%	5%
Bilirubin increased	21%	0
Magnesium decreased	21%	0
Alkaline phosphatase increased	16%	0
Potassium increased	16%	0

^aLaboratory abnormality was defined as new or worsened by at least one grade from baseline or if baseline was unknown.

Dose modifications¹

Dose discontinuations, interruptions, and reductions

• Permanent discontinuation of TIBSOVO due to an adverse reaction occurred in one (5%) patient. The adverse reaction that resulted in permanent discontinuation of TIBSOVO 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

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