Servier Canada
TIBSOVO®
PrTIBSOVO® (ivosidenib)

Focus on differentiation syndrome

What is differentiation syndrome?

Differentiation syndrome is a serious, potentially fatal condition that can occur in patients with AML treated with TIBSOVO®. It is associated with rapid proliferation and differentiation of myeloid cells.

Symptoms may include non-infectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome and creatinine increased.

How should differentiation syndrome be managed?

If differentiation syndrome is suspected, administer systemic corticosteroid therapy for a minimum of 3 days, and taper only after symptom resolution. Premature discontinuation may result in symptom recurrence.

If leukocytosis is observed, initiate treatment with hydroxyurea according to institutional standards of care and leukapheresis as clinically indicated.

Initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days.

Interrupt TIBSOVO® if severe signs/symptoms persist for more than 48 hours after initiation of systemic corticosteroids.

Resume treatment at 500 mg TIBSOVO® once daily, when signs/symptoms are moderate or lower, and upon improvement in clinical condition.

What should the patient do?

Please recommend to your patients taking TIBSOVO® that they read and understand the patient medication information leaflet that comes with their TIBSOVO® medication.

Patients must be informed of signs and symptoms of differentiation syndrome, be advised to contact their health professional immediately if these occur and the need to carry the Patient Alert Card with them at all times.

Consult the TIBSOVO® Product Monograph

2-HG: 2-hydroxyglutarate; α-KG: alpha-ketoglutarate; AML: acute myeloid leukemia; AZA: azacitidine; PBO: placebo; CCA: cholangiocarcinoma; CI: confidence interval; CR: complete response; CRh: complete response with partial hematologic recovery; CTCAE: Common Terminology Criteria for Adverse Events; DLCO: diffusing capacity for carbon monoxide; ECG: electrocardiogram; ECOG PS: Eastern Cooperative Oncology Group Performance Status; EFS: event-free survival; eGFR: estimated glomerular filtration rate; FEV1: forced expiratory volume in 1 second; HR: hazard ratio; IDH1: isocitrate dehydrogenase-1; IRC: Independent Radiology Centre; IV: intravenous; mIDH1: mutated isocitrate dehydrogenase-1; MOA: mechanism of action; NCCN: National Comprehensive Cancer Network; OR: odds ratio; OS: overall survival; PBO: placebo; PCR: polymerase chain reaction; PD: pharmacodynamics; PK: pharmacokinetics; QD: daily; RECIST: Response Evaluation Criteria In Solid Tumors; SC: subcutaneous.

References:

  1. TIBSOVO® Product Monograph. Servier Canada. July 19, 2024.
  2. Montesinos P, et al. N Engl J Med. 2022 Apr 21;386(16):1519–1531.
  3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Myeloid Leukemia Version 2.2025 — January 27, 2025.
  4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Biliary Duct Cancers Version 6.2024 — January 10, 2025.
  5. Abou-Alfa GK, et al. Lancet Oncol. 2020 Jun;21(6):796-807.
  6. Zhu AX, et al. JAMA Oncol. 2021 Nov 1;7(11):1669-1677.
  7. Dammacco F, Silvestris F, eds. Oncogenomics: From Basic Research to Precision Medicine. Academic Press; 2019.
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