TIBSOVO (ivosidenib tablets) monotherapy was studied in a patient population reflective of that seen in clinical practice1
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% |
IDH1 mutation | |
R132C | 59% |
R132H | 25% |
R132G | 7% |
R132S | 6% |
R132L | 4% |
Cytogenetic risk status | |
Intermediate | 60% |
Poor | 27% |
Missing/unknown | 13% |
Relapse type | |
Primary refractory | 37% |
Refractory relapse | 26% |
Untreated relapse | 37% |
Prior stem cell transplantation for AML | 23% |
Transfusion dependent at baselinea | 63% |
Type of AML | |
De novo AML | 67% |
Secondary AML | 33% |
AML, acute myeloid leukemia; ECOG PS, Eastern Cooperative Oncology Group Performance Status; IDH1, isocitrate dehydrogenase-1; RBC, red blood cell.
aPatients were defined as transfusion dependent at baseline if they received any RBC or platelet transfusion occurring within 56 days prior to the first dose of TIBSOVO.1
Many patients in the study had challenging disease characteristics1,2

63% of patients (109/174) were refractory to therapy1
58% of patients had ≥2 prior anticancer therapies2
- Median number of prior therapies (min, max): 2 (1, 6)1
33% of patients had secondary AML1
23% of patients had prior stem cell transplantation for AML1
87% of patients had intermediate or poor cytogenic risk status1
TIBSOVO monotherapy delivered strong responses as a once-daily oral treatment in a difficult-to-treat disease1

33% of patients (57/174) achieved CR or CRh (95% CI, 25.8‑40.3)1
- CR+CRh rate appeared to be consistent across all baseline demographic and baseline disease characteristics with the exception of number of prior regimens1
AML, acute myeloid leukemia.
Patients achieved CR or CRh after receiving 1 or more prior regimens2

47% of R/R patients who had received 1 prior regimen (35/74) achieved CR or CRh (95% CI, 35.6-59.3)2

30% of R/R patients who had received 2 prior regimens (15/50) achieved CR or CRh (95% CI, 17.9-44.6)2

15% of R/R patients who had received ≥3 prior regimens (7/48) achieved CR or CRh (95% CI, 6.1-27.8)2
CR, complete remission, defined as <5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets >100,000/µL and absolute neutrophil counts >1000/µL)2; CRh, complete remission with partial hematological recovery, defined as <5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/µL and absolute neutrophil counts >500/µL)2; R/R. relapsed or refractory.
TIBSOVO monotherapy provided durable responses1


bDuration of CR and CR+CRh were defined as time since first response of CR or CR/CRh, respectively, to relapse or death, whichever was earlier.1
36% of patients who achieved CR or CRh had ongoing responses with TIBSOVO at 12 months based on Kaplan-Meier estimation2
- Median treatment duration: 4.1 months (range, 0.1-39.5)1
- Median follow-up: 8.3 months (range, 0.2-39.5)1
TIBSOVO monotherapy enabled strong and rapid responses1,3
Time to response in patients who achieved CR or CRh


TIME (MONTHS)
Median time to first response: 1.9 months (range, 0.8‑4.7)3
Median time to CR or CRh: 2 months (range, 0.9‑5.6)1
Latest CR or CRh was achieved: 5.6 months1
~1 month
Decrease in bone marrow blasts and increase in neutrophil counts3
Earliest CR or CRh was achieved: 0.9 months1
- 100% of patients taking TIBSOVO who achieved CR or CRh reached this milestone within 6 months1
- For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response1
Transfusion independence was seen in 37% of transfusion-dependent patients who received TIBSOVO monotherapy1

37% of patients who were transfusion dependent at baseline (41/110) became transfusion independent1
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 red blood cell or platelet transfusions within 56 days prior to the first dose of TIBSOVO. Patients were defined as transfusion independent if they became independent of transfusions during any 56-consecutive day postbaseline period.1
TIBSOVO monotherapy enabled improvements in key hematologic parameters3
TIBSOVO demonstrated an improvement in hematologic variables together with a reduction in bone marrow blasts
INCREASE IN MEAN PLATELET COUNT AND MEAN ABSOLUTE NEUTROPHIL COUNTS


INCREASE IN MEAN HEMOGLOBIN LEVEL, DECREASE IN MEAN BONE MARROW BLASTS


Adapted with permission from DiNardo et al.3
Data are mean values with standard deviations.
12% of patients (21/174) went on to receive a stem cell transplant following treatment with TIBSOVO1
TIBSOVO® was studied as a single agent in both the newly diagnosed and R/R AML settings1
TIBSOVO is a first-in-class agent that inhibits the mutant IDH1 enzyme to induce myeloid differentiation1,2
- The pivotal trial for TIBSOVO monotherapy 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 RealTimeTM IDH1 assay, which is the FDA-approved test for selection of patients with AML for treatment with TIBSOVO1,3
- 28 IC-ineligible patients with newly diagnosed AML were evaluated for safety and efficacy
- 179 patients were evaluated for safety and 174 for efficacy in the R/R AML population
Efficacy was established based on the rate of CR and/or CRh, duration of CR+CRh, as well as the rate of conversion from transfusion dependence to transfusion independence1
INDICATIONS
TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for patients with a susceptible 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
- Adult patients with relapsed or refractory AML.
IMPORTANT SAFETY INFORMATION
WARNING: DIFFERENTIATION SYNDROME IN AML
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.