Safety and Efficacy of Ivosidenib Based Regimen in Patients with IDH1 Mutanted Acute Myeloid Leukemia: A Retrospective Case Series
Authors: Zhao Limin , Liu Ligen , Yang Li , Chen Fangli , Jiang Xuewei , Zhang Tinghua , Zhang Zhizhi , Zhou Xiang , Chang Li , Zhu Xinying , Du Chao , Ying Chunrong 
Published: December 2024

Patients with IDH1-mutated acute myeloid leukemia (AML) are associated with poor prognosis, and the administration of IDH1 inhibitors show the significant therapeutic effect in such patients. Due to the low frequency of IDH1 mutations and the late approve of ivosidenib in China, there are few real-world data about the usage of ivosidenib in Chinese IDH1-mutated AML patients. We respectively analyzed the usage of ivosidenib based regimen in four IDH1-muteted AML patients in four different scenes, all patients obtained very nice efficiency and safety.
The data of four IDH1-mutated AML patients admitted from May 2018 to May 2024 were collected retrospectively and analyzed. Prognostic stratification was conducted according to the 2022 ELN genetic risk stratification. Adverse events (AEs) were extracted from electronic medical records. Patient responses were assessed according to consensus guidelines.
Two were newly diagnosed, one with incomplete remission (CRi) and one with refractory. All patients were female. The ages at admission were 65 years-old (Patient 1, Pt 1), 59 (Pt 2), 67 (Pt 3) and 60 (Pt 4), respectively.
Two newly diagnosed patients had an ECOG performance status score of 1 and belonged to the intermediate cytogenetic risk group, IDH1 VAF were 15.7% and 42.5% respectively. There were concomitant DNMT3A and NPM1 mutations in Pt 1, FLT-3 TKD mutation in Pt 2.
Pt1 achieved CR after one cycle of 7+3 induction therapy. Ivosidenib was added on the third day following the second cycle of consolidation therapy with intermediate dose cytarabine, and the patient has continued on ivosidenib maintenance therapy. In the fifth month after the start of induction therapy, the patient achieved measurable residual disease (MRD) negative status. As of July 1, 2024, the patient's CR has lasted for over 18 months. During the treatment period, the dose of ivosidenib for the patient was reduced to 250 mg/d because of the fiery hyperplasia of widely adenopathy, and the patient's VAF value rapidly increased to 2.5%. After resuming ivosidenib at 500 mg/d, the patient's VAF value decreased to complete clearance. Pt 2, due to a lung infection at diagnosis, received ivosidenib combined with azacitidine. Fourteen days after treatment initiation, the blast count in bone marrow dropped to 4%, and the patient has maintained a CR with a response duration of 138 days. In Pt3 and Pt4, IDH1 VAFs were 33% and 44.9%, there were concomitant FLT-3 ITD, NPM1, KRAS, and DNMT3A mutations in Pt3, FLT-3 TKD, DNMT3A, PHF6, and TP53 mutations in Pt4. Pt3 received the DLAAG regimen, and a subsequent bone marrow examination showed 78% blasts. After adding gilteritinib for the FLT-3 mutation, one month later showed a reduction to 19% blasts, and then switched to a regimen of azacitidine, venetoclax, selinexor, and ivosidenib. After 30 days, the patient achieved CR with incomplete hematologic recovery, and 35 days later, the patient achieved MRD- CR. As of now (1 Jul 2024), the CR has lasted over 20 months, and the overall survival since diagnosis is over 31 months. Pt 4 achieved CRi with the DLAAG plus venetoclax regimen after relapse. Due to recurrent severe infection, the patient was switched to ivosidenib maintenance therapy. After one week, the neutrophil count was normal and patient achieved CR, and also the recurrent infection was resolved. The patient has remained on ivosidenib, with CR lasting over 65 months and overall survival since diagnosis exceeding 94 months.
Pt 1 experienced grade 4 neutropenia and grade 3 rash during ivosidenib plus cytarabine consolidation therapy, leading to temporary discontinuation of ivosidenib. During maintenance, the patient was co-administered cetirizine, with no reported AEs. Pt 2/3/4 did not report any significant AEs.
Our data show that ivosidenib-based treatment was successful in four Chinese AML patients with IDH1 mutations, demonstrating that the low toxicity allows for long-term administration. All patients achieved or maintained CR, with a favorable response and prolonged duration of remission. Further studies with larger cohorts are necessary to confirm these findings.