NEWLY APPROVED DRUGS
The Year in FDA Approvals
In the past year, the U.S. Food and Drug Administration
(FDA) approved several therapies for the treatment of
myeloid malignancies, including the first treatment
approved for blastic plasmacytoid dendritic cell neoplasm
(BPDCN). Here, we review the regulatory approvals since
our last “Focus on Myeloid Malignancies” special edition
published in May 2018.
The most common adverse events (AEs; occurring in ≥20%
of patients) associated with ivosidenib included fatigue, leuko-
cytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis,
prolonged electrocardiogram QT interval, rash, pyrexia, cough,
and constipation.
Ivosidenib was approved through the priority-review
pathway and with fast-track and orphan-product designations.
Studies of ivosidenib in combination with other therapies and in
newly diagnosed AML are ongoing.
Ivosidenib
On July 20, 2018, the FDA approved ivosidenib, a small-molecule
IDH1 inhibitor, for the treatment of adult patients with relapsed or
refractory acute myeloid leukemia (AML) and an IDH1 mutation.
This is the first IDH1 inhibitor approved for this indication, and the
agent was approved simultaneously with the RealTime IDH1 assay,
a companion diagnostic designed to detect the IDH1 mutation.
The FDA based its approval decision on data from a single-
arm study that evaluated the efficacy of ivosidenib in 174 pa-
tients with relapsed or refractory IDH1-mutated AML. After a
median follow-up of 8.3 months (range = 0.2-39.5 months), 32.8
percent of patients experienced complete remission (CR) or CR
with partial hematologic recovery (CRh). The median time to re-
sponse was 2.0 months (range = 0.9-5.6 months), and responses
lasted for a median of 8.2 months (range = 5.6-12 months).
In addition, of the 110 participants who were red blood
cell (RBC) or platelet transfusion–dependent at baseline, 41
(37.3%) went at least 56 days without requiring a transfusion
after ivosidenib treatment.
Glasdegib
On November 23, 2018, the FDA approved glasdegib, in combina-
tion with low-dose cytarabine, for patients with newly diagnosed
AML who are age 75 or older or who have comorbidities that
preclude the use of intensive induction chemotherapy.
The agency’s decision was based on results from the multi-
center, open-label BRIGHT AML 1003 study, which included
115 patients with AML who met at least one of the following
criteria: aged 75 years or older, severe cardiac disease, Eastern
Cooperative Oncology Group performance status score of 2, or
baseline serum creatinine >1.3 mg/dL.
Patients were randomized 2:1 to receive glasdegib 100 mg/day
with low-dose cytarabine (20 mg subcutaneously twice daily on
days 1-10 of a 28-day cycle; n=77) or low-dose cytarabine alone
(n=38).
With a median follow-up of 20 months (range not reported),
median overall survival was 8.3 months (range = 4.4-12.2 months)
May 2019
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