Dosage & Administration
Select patients based on presence of IDH1 mutation(s). (
Select patients for the treatment of relapsed or refractory AML with REZLIDHIA based on the presence of IDH1 mutations in blood or bone marrow
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Rezlidhia Prescribing Information
REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% (25/153) of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients [see Adverse Reactions (6.1)]. 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 REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dosage interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis.
If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence
REZLIDHIA 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
Select patients for the treatment of relapsed or refractory AML with REZLIDHIA based on the presence of IDH1 mutations in blood or bone marrow
Olutasidenib is a small-molecule inhibitor of mutated isocitrate dehydrogenase-1 (IDH1). In patients with AML, susceptible IDH1 mutations are defined as those leading to increased levels of 2-hydroxyglutarate (2-HG) in the leukemia cells and where efficacy is predicted by 1) clinically meaningful remissions with the recommended dose of olutasidenib and/or 2) inhibition of mutant IDH1 enzymatic activity at concentrations of olutasidenib sustainable at the recommended dosage according to validated methods. The most common of such mutations in patients with AML are R132H and R132C substitutions.
In vitro, olutasidenib inhibited mutated IDH1 R132H, R132L, R132S, R132G, and R132C proteins; wild-type IDH1 or mutated IDH2 proteins were not inhibited. Olutasidenib inhibition of mutant IDH1 led to decreased 2-HG levels in vitro and in in vivo xenograft models.
The efficacy of REZLIDHIA was evaluated in an open-label, single-arm, multicenter clinical trial (Study 2102-HEM-101, NCT02719574) in 147 adult patients with relapsed or refractory AML with an IDH1 mutation.
IDH1 mutations in blood or bone marrow were confirmed retrospectively using the Abbott RealTi
The baseline demographic and disease characteristics are shown in Table 4.
Demographic and Disease Characteristics | REZLIDHIA (150 mg twice daily) N=147 |
Demographics | |
Age (Years) Median (Min, Max) | 71 (32, 87) |
Age Categories, n (%) | |
| <65 years | 37 (25) |
| ≥65 years to <75 years | 65 (44) |
| ≥75 years | 45 (31) |
Sex, n (%) | |
| Male | 74 (50) |
| Female | 73 (50) |
Race, n (%) | |
| White | 67 (46) |
| Black or African American | 5 (3) |
| Asian | 5 (3) |
| Native Hawaiian/Other Pacific Islander | 0 (0) |
| Other/Not provided | 70 (48) |
Disease Characteristics | |
ECOG PS, n (%) | |
| 0 | 45 (31) |
| 1 | 76 (52) |
| 2 | 23 (16) |
IDH1 Mutation, n (%)Using central IDH1 assay testing results. | |
| R132C | 85 (58) |
| R132H | 35 (24) |
| R132G | 12 (8) |
| R132S | 11 (7) |
| R132L | 4 (3) |
Type of AML, n (%) | |
| De novo AML | 97 (66) |
| Secondary AML | 50 (34) |
Cytogenetic Risk StatusCytogenetic risk categorization was investigator reported by NCCN or ELN guidelines., n (%) | |
| Favorable | 6 (4) |
| Intermediate | 107 (73) |
| Poor | 25 (17) |
| Unknown | 9 (6) |
Relapsed/Refractory Patient Category | |
| Primary Refractory | 46 (31) |
| Untreated RelapseMay be first or subsequent relapse. | 81 (55) |
| Refractory Relapse | 20 (14) |
Relapse Number | |
| 0 | 46 (31) |
| 1 | 87 (59) |
| 2 | 11 (8) |
| ≥3 | 3 (2) |
Prior Stem Cell Transplantation for AML, n (%) | 17 (12) |
Transfusion Dependent at BaselineTransfusion-Dependent at Baseline is defined as receiving a transfusion within 8 weeks prior to first dose of olutasidenib or noting transfusion dependence prior to coming on study., n (%) | 86 (59) |
Median Number of Prior Therapies (Min, Max) | 2 (1,7) |
Efficacy was established on the basis of the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to transfusion independence. The efficacy results are shown in Table 5. The median follow-up was 10.2 months (range: 0.2 to 38.1 months) and median treatment duration was 4.7 months (range: 0.1 to 26.0 months).
Endpoint | REZLIDHIA (150 mg twice daily) N=147 |
CR+CRhCR (complete remission) was defined as <5% blasts in the bone marrow, no blasts with Auer rods, no extramedullary disease, and full recovery of peripheral blood counts (platelets >100,000/microliter and absolute neutrophil counts [ANC] >1,000/microliter); CRh (complete remission with partial hematologic recovery) was defined as <5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).,CR+CRh rate was consistent across all baseline demographic and baseline disease characteristic subgroups with the exception of IDH1 R132H mutation (CR+CRh 17%).n (%) | 51 (35) |
95% CI | (27, 43) |
Median DOCR+CRhDuration of response is defined as the time from the date of the first response to the date of the relapse or death. Patients who did not relapse were censored at the date of last response assessment. + indicates censored observation.(months) | 25.9 |
95% CI | (13.5, NR) |
CRn (%) | 47 (32) |
95% CI | (25, 40) |
Median DOCR(months) | 28.1 |
95% CI | (13.8, NR) |
CRhn (%) | 4 (2.7) |
95% CI | (0.7, 6.8) |
Observed DOCRh(months) | 1.8, 5.6, 13.5, 28.5+ |
| CI: confidence interval; NR = not reached | |
Of the patients who achieved a CR or CRh, the median time to CR or CRh was 1.9 months (range: 0.9 to 5.6 months). All patients that achieved a best response of CR or CRh did so within 5.6 months of initiating REZLIDHIA.
Overall, among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion independent during any 56-day post- baseline period.
Select patients based on presence of IDH1 mutation(s). (
Select patients for the treatment of relapsed or refractory AML with REZLIDHIA based on the presence of IDH1 mutations in blood or bone marrow
- Recommended dosage: 150 mg orally twice daily, until disease
progression or unacceptable toxicity. ()2.2 Recommended DosageThe recommended dosage of REZLIDHIA is 150 mg taken orally twice daily until disease progression or unacceptable toxicity. Administer REZLIDHIA capsules orally about the same time each day. Do not administer 2 doses within 8 hours. Take on an empty stomach at least 1 hour before or 2 hours after a meal
[see Clinical Pharmacology ]. For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response.Swallow REZLIDHIA capsules whole. Do not break, open, or chew the capsules. If a dose of REZLIDHIA is vomited, do not administer a replacement dose; wait until the next scheduled dose is due. If a dose of REZLIDHIA is missed or not taken at the usual time, administer the dose as soon as possible and at least 8 hours prior to the next scheduled dose. Return to the normal schedule the following day.
- Take on an empty stomach at least 1 hour before or 2 hours after a
meal. ()2.2 Recommended DosageThe recommended dosage of REZLIDHIA is 150 mg taken orally twice daily until disease progression or unacceptable toxicity. Administer REZLIDHIA capsules orally about the same time each day. Do not administer 2 doses within 8 hours. Take on an empty stomach at least 1 hour before or 2 hours after a meal
[see Clinical Pharmacology ]. For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response.Swallow REZLIDHIA capsules whole. Do not break, open, or chew the capsules. If a dose of REZLIDHIA is vomited, do not administer a replacement dose; wait until the next scheduled dose is due. If a dose of REZLIDHIA is missed or not taken at the usual time, administer the dose as soon as possible and at least 8 hours prior to the next scheduled dose. Return to the normal schedule the following day.
Capsules: 150 mg opaque white capsules imprinted with "OLU 150".
Lactation: Advise not to breastfeed. (
There are no data on the presence of olutasidenib or its metabolites in human milk, the effects on the breastfed child, or milk production. Because many drugs are excreted in human milk, and due to the potential for adverse reactions in a breastfed child, advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.
None.