On May 25, 2022, Servier announced that the U.S. FDA had approved ivosidenib (Tibsovo) in combination with azacitidine for the treatment of newly diagnosed IDH1-mutant acute myeloid leukemia (AML) patients aged 75 years or older, or patients with comorbidities excluding those who have received intensive induction chemotherapy.
Results from the Phase 3 AGILE trial supported the expanded approval, demonstrating that ivosidenib in combination with azacitidine significantly improved event-free survival (EFS) compared to azacitidine alone (HR, 0.35; 95% CI, 0.17–0.72; two-sided P = .0038). Compared with azacitidine monotherapy, the addition of iverinib improved median overall survival (OS) to 24.0 months (95% CI, 11.3–34.1) and 7.9 months (95% CI, 4.1–11.3) (HR, 0.44; 95% CI, 0.27–0.73; P = .001).
It is worth noting that Tibsovo (ivosidenib) is an oral targeted inhibitor of isocitrate dehydrogenase 1 (IDH1), which has been approved by the FDA for adult patients with relapsed or refractory acute myeloid leukemia (R/RAML) confirmed by a assay (Abbott RealTime IDH1 companion diagnostic kit) to have a susceptible isocitrate dehydrogenase-1 (IDH1) mutation. It is the first and only drug approved by the FDA for the treatment of IDH1-mutant R/RAML.
A global, double-blind, placebo-controlled, phase 3 trial enrolled previously untreated, centrally diagnosed patients with IDH1-mutant AML who were ineligible for intensive chemotherapy.
As of the data cutoff date of March 18, 2021, 39 patients had received treatment; 38% were in the study group and 16% in the control group.
Other data published in the New England Journal of Medicine showed a complete response (CR) rate of 47% (95% CI, 35%–59%) in the ivevitinib group and 15% (95% CI, 8%–25%) in the azacitidine monotherapy group (P < .001). The median duration of CR in the ivevitinib group had not yet been reached, compared to 11.2 months in the azacitidine monotherapy group.
Among those patients who achieved complete remission, the estimated probability of maintaining complete remission within 1 year was 88% in the study group and 36% in the control group. The median time to complete remission (CR) was 4.3 months (range 1.7–9.2) in the ivosidenib/azacitidine group and 3.8 months (range 1.9–8.5) in the azacitidine monotherapy group. In the study group and control group, CR or partial hematologic recovery was observed in 53% (95% CI, 41%–65%) and 18% (95% CI, 10%–28%) of patients, respectively.
Furthermore, 62% (95% CI, 50%–74%) of patients treated with ivevitinib/azacitidine achieved an objective response, compared to 19% (95% CI, 11%–30%) of patients treated with azacitidine alone (P<.001). The median duration of response was 22.1 months (95% CI 13.0–unpredictable) and 9.2 months (95% CI 6.6–14.1), respectively.
The safety profile of this combination was consistent with previously published findings. The most common toxicities observed in newly diagnosed AML patients receiving this regimen included nausea, vomiting, QT prolongation on ECG, insomnia, dysphagia, leukocytosis, hematoma, hypertension, arthralgia, dyspnea, and headache.
In August 2021, Tibsovo (ivosidenib) received FDA approval for the treatment of cholangiocarcinoma. In China, it was approved in February of this year for the treatment of adult patients with relapsed or refractory AML harboring IDH1 mutations.
