臨床研究等提出・公開システム

VANFLYTA Tablet Post-marketing Surveillance Study

VANFLYTA Tablet Post-marketing Surveillance Study

126

The safety analysis dataset consisted of 126 patients. The median age was 63.0 years, and patients aged >=65 years accounted for 46.8% (59/126). Male patients accounted for 54.0% (68/126). An ECOG performance status of 2-4 was reported in 23.8% (30/126). Regarding relapsed or refractory status, relapsed AML was reported in 43.7% (55/126) and refractory AML in 56.3% (71/126). For AML mode of onset, secondary AML was reported in 11.1% (14/126). CNS involvement was reported in 4.8% (6/126). History of previous HSCT was reported in 29.4% (37/126). Previous use of other FLT3 inhibitors was reported in 63.5% (80/126). The median duration of quizartinib treatment was 71.0 days.

Between October 10, 2019 and December 31, 2021, 259 patients with relapsed or refractory FLT3 ITD-positive acute myeloid leukemia were treated with quizartinib at 229 institutions in Japan. Case report forms were collected from 256 patients. After exclusion of 10 patients who were duplicates (double registered at different institutions) and one patient who did not receive quizartinib, the overall safety analysis population included 245 patients. Among these, consent for publication of the results of this post marketing surveillance was obtained from 126 patients, who comprised the safety analysis dataset for publication. For the effectiveness evaluation, one patient was excluded from the safety analysis dataset due to discontinuation of quizartinib without a positive FLT3 ITD mutation test after treatment initiation; therefore, effectiveness was evaluated in 125 patients.

A total of 68 patients (54.0%) developed an ADR; 44 (34.9%) had a grade >= 3 ADR, 20 (15.9%) had a serious ADR, and 20 (15.9%) had an ADR leading to discontinuation of quizartinib. The most common ADRs of any grade were neutrophil count decreased, platelet count decreased, QT interval prolongation, anemia, and white blood cell count decreased. Grade >= 3 ADRs reported in >= 2 patients included neutrophil count decreased (n = 16; 12.7%), platelet count decreased (n = 14; 11.1%), white blood cell count decreased (n = 8; 6.3%), anemia (n = 7; 5.6%), febrile neutropenia (n = 4; 3.2%), and QT interval prolongation and hepatic function abnormal (n = 2 patients each; 1.6%). Serious ADRs that occurred in >= 2 patients were neutrophil count decreased and platelet count decreased (n = 6 patients each; 4.8%), anemia and white blood cell count decreased (n = 3 patients each; 2.4%), and febrile neutropenia (n = 2; 1.6%). ADRs leading to quizartinib discontinuation in >= 2 patients were neutrophil count decreased (n = 8; 6.3%), platelet count decreased (n = 5; 4.0%), and nausea (n = 3; 2.4%).

Safety specifications: Among 124 patients who underwent post-baseline ECG, 18 (14.5%) experienced an ADR of QT interval prolongation. These events included ECG QT prolonged in 17 patients (13.7%) and long QT syndrome in one patient (0.8%). The severity of QT interval prolongation was mostly grade 1 or 2; grade 3 prolongation was less frequent. No patients experienced clinical symptoms associated with QT interval prolongation (i.e., grade 4). The first QT interval prolongation event most commonly occurred < 30 days after quizartinib administration (8.9%), followed by 30 to < 60 days, and 150 to < 180 days (2.4% each). One patient discontinued treatment due to a quizartinib treatment-related QT interval prolongation event. According to the attending physician, all 18 patients had recovered or were recovering. The mean duration from onset of QT interval prolongation to the date of recovery or outcome assessment in all 18 patients was 24.0 +/- 27.7 days. Other safety specification events included four differentiation syndrome-like symptoms in three patients (2.4%; fever [n = 2], edema [n = 1], and rash [n = 1]), and acute kidney injury in one patient. No events related to myocardial infarction or interstitial lung disease were reported.

Effectiveness: Six months after the start of treatment, the best antitumor response was CR in 17 patients (13.6%), CRp in five patients (4.0%), and CRi in 11 patients (8.8%), for a CRc rate of 26.4%. In subgroup analyses, the CRc rate was lower in patients with prior FLT3 inhibitor therapy (15.2%) than in those without prior FLT3 inhibitor therapy (45.7%). In a post-hoc analysis, of 23 patients who discontinued other FLT3 inhibitors due to AEs, six (26.1%) achieved CRc, and of 52 patients who discontinued due to resistance to other FLT3 inhibitors, five (9.6%) achieved CRc. Hematopoietic stem cell transplantation: In the 6 months after the start of quizartinib treatment, 35 patients (28.0%) underwent allogeneic HSCT without other AML therapy. Of these, CRc was achieved by 15 patients (45.5%) and not achieved by 20 patients (21.7%).

The results of this PMS suggest that the safety profile of quizartinib in patients with R/R FLT3-ITD-positive AML treated in routine clinical practice in Japan did not differ from the known safety profile of quizartinib, especially with regard to QT interval prolongation. No new safety concerns were identified. QT interval prolongation in patients treated with quizartinib can be managed with current risk minimization measures.

Feb. 26, 2026

https://doi.org/10.1007/s12185-026-04181-7

No

Tanabe Hirokazu

DAIICHI SANKYO CO., LTD.

3-5-1,Nihonbashi Honcho,Chuo-ku,Tokyo

contact_gpsp_jp@daiichisankyo.com

Contact for GPSP

DAIICHI SANKYO CO., LTD.

3-5-1,Nihonbashi Honcho,Chuo-ku,Tokyo

+81-3-6225-1059

contact_gpsp_jp@daiichisankyo.com

completed

Oct. 10, 2019

Observational

Observational surveillance (Post-marketing surveillance)

other

N/A

All patients who start receiving VANFLYTA Tablet during the registration period.

Patients with a previous history of hypersensitivity to the ingredients of VANFLYTA.

Both

Relapsed or refractory acute myeloid leukemia with FLT3-ITD mutation positive

safety
Information about the adverse events that have occurred, by adverse reaction/infection category.
Information about the safety specifications concerns that have occurred.

efficacy
Best antitumor response