Real-world survival of IDH-mutant patients in China before IDH-inhibitor era: A multicenter retrospective study from anhui cooperative hematology group(ACHG) Free

The impact of IDH mutations on the survival of AML patients is unclear. Since the VIALE-A study shows improved survival for patients with IDH mutations, many patients have received azacitidine plus venetoclax treatment before the approval of the IDH inhibitor in China. Here, we aim to show the survival of IDH mutated patients in China without IDH inhibitors.

From January 2017 to December 2024, 726 patients were diagnosed with de novo AML at three medical centers in Anhui Province, China (the First Affiliated Hospital of Anhui Medical University, First Affiliated Hospital of Bengbu Medical University, the First Affiliated Hospital of Wannan Medical College) with available next-generation sequencing results, and did not received treatment including IDH inhibitor. A total of 619 patients have been identified as wild-type IDH (IDH^wt), 42 patients have been identified as IDH1 mutation (IDH1^mut), and 65 patients have been identified as IDH2 mutation (IDH2^mut). The median age of IDH1^mut and IDH2^mut patients at the time of diagnosis is 59.2 and 59.5 years, respectively, which was statistically older to IDH^wt patients (50.9 years, p<0.05).

After the first induction therapy, which mainly include cytarabine based intensive chemotherapy and azacitidine plus venetoclax treatment, 64.8%, 52.4%, and 55.4% of patients in the IDH^wt, IDH1^mut, and IDH2^mut groups, respectively, have achieved complete remission (CR). The median overall survival (OS) of the IDH^wt group is 19.1 months, which is between the IDH2^mut group (38.9 months, p=0.736) and the IDH1^mut group (7.6 months, p=0.155).

There are 354 IDH^wt, 16 IDH1^mut and 33 IDH2^mut patients who received intensive cytarabine- based chemotherapy without venetoclax. The IDH2^mut group shows a similar long-term survival to the IDH^wt group (median OS, 38.9 vs. 37.1 months, p=0.275). However, the median OS of the IDH1^mut group is only 9.8 months, which is significantly worse than the IDH^wt group (p=0.036).

After the approval of venetoclax for AML in China, 110 IDH^wt patients, 14 IDH1^mut patients and 17 IDH2^mut patients received azacitidine plus venetoclax treatment. The median OS of these IDH1^mut patients unfit for intensive chemotherapy is 13.3 months, same as other IDH2^mut and IDH^wt patients who received azacitidine plus venetoclax treatment (median OS, IDH2^mut not reached, IDH^wt 13.1 months). These findings suggest that venetoclax treatment prolonged survival in “unfit” IDH1^mut patients compared to intensive chemotherapy.

Our multicenter study shows that the real-world survival of IDH1^mut patients is significantly shorter than that of other patients with IDH2^mut and IDH^wt when receiving intensive cytarabine-based chemotherapy without venetoclax. Azacitidine plus venetoclax treatment improve the survival of IDH1^mut patients to the same level as other patients with IDH2^mut and IDH^wt. Given the AGILE study of azacitidine plus ivosidenib in newly diagnosed IDH1-mutated AML shows a longer median OS (29.3 months), we recommend that IDH1^mut patients who are unable to access IDH1 inhibitors consider venetoclax-based treatment as a potential strategy to enhance survival outcomes.