NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend ivosidenib (TIBSOVO®) in R/R AML with an IDH1 mutation1

TIBSOVO® was studied as a single agent in patients with R/R AML with an IDH1 mutation1

TIBSOVO is a first-in-class agent that inhibits the mutant IDH1 enzyme to induce myeloid differentiation1

  • The pivotal trial for TIBSOVO was an open-label, single-arm, multicenter trial1
  • IDH1 mutations were identified by a local or central diagnostic test and confirmed retrospectively using the Abbott RealTime™ IDH1 Assay, which is the FDA-approved test for selection of patients with R/R AML for treatment with TIBSOVO1
Patients with R/R AML and an IDH1 mutation were assigned a starting dose of TIBSOVO 500 mg daily and received treatment until disease progression, development of unacceptable toxicity, or undergoing hematopoietic stem cell transplantation.1

Efficacy was established based on the rate and duration of CR+CRh, as well as on the rate of conversion from transfusion dependence to transfusion independence1

CR, complete remission; CRh, complete remission with partial hematological recovery; R/R, relapsed or refractory.

TIBSOVO was studied in a patient population with difficult to treat disease1

Patient characteristics were reflective of those seen in clinical practice

Selected baseline demographic and disease characteristics (N=174)1
Median age (years) (min, max) 67 (18,87)
ECOG PS
0 21%
1 56%
2 22%
3 1%
Cytogenetic risk status
Intermediate 60%
Poor 27%
Missing/unknown 13%
IDH1 mutation
R132C 59%
R132H 25%
R132G 7%
R132S 6%
R132L 4%
Transfusion dependent at baselinea 63%
aPatients were defined as transfusion dependent at baseline if they received any transfusion occurring within 56 days prior to the first dose of TIBSOVO.1
ECOG PS, Eastern Cooperative Oncology Group Performance Status.
63

Patients were refractory to therapy1

  • 37% were primary refractory
  • 26% were refractory in relapse
58

Patients had ≥2 prior anticancer therapies2

  • Median number of prior therapies (min, max): 2 (1, 6)1
23

Prior stem cell transplantation for AML1

33

Patients had secondary AML1

TIBSOVO delivered strong and durable responses as a single agent1

In a population with difficult-to-treat R/R AML with an IDH1 mutation (N=174)1:
33% of patients (57/174) achieved CR or CRh (95% CI, 25.8-40.3)1
  • 24.7% CR rate (43/174) (95% CI, 18.5-31.8);
    8.0% CRh rate (14/174) (95% CI, 4.5-13.1)1
  • CR+CRh rate appeared to be consistent across all baseline demographic and baseline disease characteristics with the exception of number of prior regimens1
47.3% of patients who had received 1 prior regimen (35/74) achieved CR or CRh (95% CI, 35.6-59.3)2

Complete remission (CR) was defined as1:

  • <5% blasts in the bone marrow
  • No evidence of disease
  • Full recovery of peripheral blood counts
    • Platelets >100,000/microliter and absolute neutrophil counts >1000/microliter

Complete remission with partial hematological recovery (CRh) was defined as1:

  • <5% blasts in the bone marrow
  • No evidence of disease
  • Partial recovery of peripheral blood counts
    • Platelets >50,000/microliter and absolute neutrophil counts >500/microliter
Medium Duration of Response, Graph
  • Median treatment duration: 4.1 months (range, 0.1-39.5 months)1
  • Median follow-up: 8.3 months (range, 0.2-39.5 months)1
aDuration of response was defined as time since first response of CR or CRh to relapse or death, whichever is earlier.1

Transfusion independence was seen in some patients who received TIBSOVO1

37% of patients who were transfusion dependent at baseline (41/110) became transfusion independent1
  • 20.0% (22/110)2

    Patients who achieved CR or CRh

  • 17.3% (19/110)2

    Patients who did not achieve CR or CRh

  • 59% of patients who were transfusion independent at baseline (38/64) remained so1

Patients were defined as transfusion dependent at baseline if they received any RBC or platelet transfusions within 56 days prior to the first dose of TIBSOVO. Patients were defined as transfusion independent postbaseline if they received no RBC or platelet transfusions during any 56-consecutive day period during treatment with TIBSOVO.1

12% of patients (21/174) went on to receive a stem cell transplant following treatment with TIBSOVO1
RBC, red blood cell.

Patients should remain on TIBSOVO until disease progression or unacceptable toxicity1

For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response1

Time to CR or CRh, Graph
  • For patients who achieved a CR or CRh, median time to CR or CRh: 2 months (range, 0.9-5.6 months)1
References: 1. TIBSOVO [package insert]. Cambridge, MA: Agios Pharmaceuticals, Inc.; 2018. 2. Data on file. Agios Pharmaceuticals, Inc.
 
 

INDICATION

TIBSOVO® (ivosidenib) is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) 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

Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. 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.