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Letters to the Editor
including 51 in the conventional-dose group and 38 in the intermediate-dose group. There were 66 patients with FLT3-ITD mutations, regardless of NPM1 mutations, including 35 in the conventional-dose group and 31 in the intermediate-dose group. Intermediate-dose cytarabine did not increase the complete remission rate or improve RFS, EFS, or OS compared to conventional-dose cytarabine in patients with NPM1 or FLT3-ITD mutations, as shown in Online Supplementary Table S2. In patients with NPM1 mutations, the 5-year RFS, EFS, and OS rates were 68%, 63%, and 70% in the intermediate-dose cytarabine group compared to 61%, 53%, and 65% (Figure 3A-C), respec- tively, in the conventional-dose group. In patients with FLT3-ITD mutations, the 5-year RFS, EFS, and OS rates were 68%, 48%, and 58% in the intermediate-dose cytara- bine group compared to 50%, 34%, and 45% (Figure 3D- F), respectively, in the conventional-dose group. We then investigated the impact of intermediate-dose cytarabine in NPM1+/FLT3-ITD–, NPM1+/FLT3–ITD+, and NPM1–/FLT3- ITD+ subgroups. Intermediate-dose cytarabine did not increase complete remission rate or improve RFS, EFS, or OS compared to conventional-dose cytarabine in all these subgroups, as shown in Online Supplementary Table S3.
Death rates within 30 days were similar in the interme- diate- and conventional-dose cytarabine induction cohorts.2 There were no significant differences in RFS, OS, cumulative incidence of relapse or cumulative incidence of death in complete remission between the consolidation regimens even with longer follow-up (data not shown). With inclusion of the second randomization in multivariable analyses, the conclusions regarding outcomes depending on induction treatment were not modified by the second randomization, as shown in Online Supplementary Table S4, except that the OS in the intermediate cytogenetic-risk group was not significantly different, but with a trend, and no difference in EFS in the poor cytogenetic-risk group.
In this subgroup analysis with updated follow-up, we demonstrated that AML patients with CEBPAdm and RUNX1-RUNX1T1 might benefit from intermediate-dose cytarabine induction. AML patients with CEBPAdm had a more favorable RFS than others only when treated with intermediate-dose cytarabine induction. Intermediate-dose cytarabine did not, however, improve outcomes in AML patients with NPM1 or FLT3-ITD mutations. Luskin et al. suggested that anthracycline dose intensification induction conferred a favorable prognosis for AML patients with NPM1 mutations.7 These data indicate that AML patients with different mutations might benefit from intensified doses of different drugs. Recently, novel drugs, such as gemtuzumab ozogamicin, FLT3 inhibitors and so on, are being used in clinical practice. Prospective trials would be needed to confirm the benefit of induction with intermedi- ate-dose cytarabine, especially when novel drugs are used.
Hui Wei,1,2,3 Chunlin Zhou,3 Dong Lin,3 Bingcheng Liu,3 Yan Li,3 Xingli Zhao,3 Shuning Wei,3 Benfa Gong,3
Kaiqi Liu,3 Xiaoyuan Gong,3 Yuntao Liu,3 Guangji Zhang,3 Jiayuan Chen,1 Junping Zhang,3 Jingjing Jin,3 Shaowei Qiu,3 Runxia Gu,3 Ying Wang,2,3 Yingchang Mi1,2,3
and Jianxiang Wang1,2,3
1State Key laboratory of Experimental Hematology; 2National Clinical Research Center for Blood Diseases and 3Leukemia Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China
Correspondence:
JIANXIANG WANG - wangjx@ihcams.ac.cn doi:10.3324/haematol.2020.267526
Received: July 19, 2020.
Accepted: September 15, 2020. Pre-published: September 28, 2020. Disclosures: no conflicts of interest to disclose.
Contributions: JW and HW contributed to the study design;
JW, HW, and JC were involved in analyzing and interpreting the data; JW and HW wrote the report. All authors were involved in the collec- tion and assembly of clinical data. HW, DL, CZ, BL, SQ, RG, YL, XZ, SW, BG, KL, XG, YLiu, GZ, JZ, JJ, YW and YM provided the study materials or patients. All authors reviewed the report and approved the final version.
Funding: this study was supported in part by funds from: the State Key Program of National Natural Science of China (81830005) and the CAMS Innovation Fund for Medical Sciences (2019-I2M-2-009) to JW; the National Key Research and Development Program of China (2019YFC0840605) to YM; and the National Natural Science Foundation of China (81670159) and Tianjin Natural Science Foundation (18JCZDJC45000) to HW. The funders had no role in the study design, analyses, or decision to publish.
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