Dataset Information

Decitabine in patients with myelodysplastic syndromes: A multi-center, open-label, dose comparison trial.

ABSTRACT:

Background

The hypomethylating agent decitabine is the standard therapy for intermediate or high risk myelodysplastic syndrome (MDS).

Methods

In this trial, 191 adult patients with intermediate/high risk MDS (IPSS score ≥ 0.5) randomly received decitabine using a standard regimen (20 mg/m² /day for 5 consecutive days; n = 94) or an extended regimen with lower daily dose (12 mg/m² /day for 8 consecutive days; n = 97) every 4 weeks, for a total of 4 cycles.

Results

The median follow-up was 14 months (range 2-36). The primary end point of overall response rate in the intent-to-treat analysis was 41.5% and 38.1% in the standard and extended dosing arms, respectively (p = 0.660). Complete remission and marrow complete remission also did not differ between the two arms. Cytopenia was the most frequent adverse event (76.4%). The median duration of neutropenia per cycle did not differ between the two arms during the first two cycles, but significantly shorter in the extended dosing arm in the third cycle (8.5 vs. 15.5 days, p = 0.049) and in the fourth cycle (8 vs. 14 days, p = 0.294).

Conclusion

The 5-day 20-mg/m² /day and 8-day 12-mg/m² /day decitabine regimens have similar efficacy and safety in patients with intermediate or high risk MDS.

SUBMITTER: Liu H

PROVIDER: S-EPMC10358210 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Decitabine in patients with myelodysplastic syndromes: A multi-center, open-label, dose comparison trial.

Liu Hui H Jiang Hao H Tong Hongyan H Xia Ruixiang R Yang Linhua L Zhao Hongguo H Ouyang Jian J Bai Hai H Sun Hui H Hou Li L Jiang Ming M Zeng Yun Y Liu Zhuogang Z Liang Aibin A Xie Yinghua Y Yu Kang K Zhai Zhimin Z Liu Li L Jia Jinsong J Fu Rong R Shao Zonghong Z

Cancer medicine 20230623 13

<h4>Background</h4>The hypomethylating agent decitabine is the standard therapy for intermediate or high risk myelodysplastic syndrome (MDS).<h4>Methods</h4>In this trial, 191 adult patients with intermediate/high risk MDS (IPSS score ≥ 0.5) randomly received decitabine using a standard regimen (20 mg/m<sup>2</sup> /day for 5 consecutive days; n = 94) or an extended regimen with lower daily dose (12 mg/m<sup>2</sup> /day for 8 consecutive days; n = 97) every 4 weeks, for a total of 4 cycles.<h4> ...[more]

PMID: 37350499

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Project description:IntroductionThe objective of this study was to evaluate the efficacy and safety of decitabine in Chinese patients with myelodysplastic syndrome (MDS).MethodsPatients (≥18 years) who had a de novo or secondary MDS diagnosis according to French-American-British classification and an International Prognostic Scoring System score ≥0.5 were enrolled and randomized (1:1) to one of two decitabine regimens: 3-day treatment (3-h intravenous infusion of 15 mg/m(2) given every 8 h for three consecutive days/cycle/6 weeks) or 5-day treatment (1-h intravenous infusion of 20 mg/m(2) once daily on days 1-5/cycle/4 weeks). After a minimum of 30 patients were assigned to 3-day schedule, the remaining were assigned to the 5-day schedule. The primary efficacy endpoint was the overall response rate (ORR). Secondary outcome measures included hematologic improvement (HI), cytogenetic response rate, the time to acute myeloid leukemia (AML) progression, and overall survival (OS).ResultsIn total, 132 of 135 enrolled patients (3-day treatment, n = 36; 5-day treatment, n = 99) discontinued treatment (major reasons included patient withdrawal/lack of efficacy, n = 48; adverse events, n = 23; and disease progression, n = 22). During the study, 35 of 132 (26.5%) patients from the intent-to-treat (ITT) group achieved significant (P < 0.001) ORR [3-day group (n = 10, 29.4%), P = 0.003; 5-day group (n = 25, 25.5%), P < 0.001]. The HI rate was similar between the 3-day (47.1%) and 5-day groups (48.0%). Cytogenetic response was achieved in 20 of the 30 (66.7%) patients who had a baseline cytogenetic abnormality. Fifty-three (40.2%) AML transformations or deaths occurred and the median AML-free survival time was 23.8 months for all patients from the ITT set; 24-month OS rate was 48.9%. Adverse events of myelosuppression-related disorders (85.6%) and infections (43.2%) were commonly reported.ConclusionDecitabine treatment was efficacious in Chinese patients with MDS with its safety profile comparable to the global studies of decitabine conducted to date.FundingXian-Janssen Pharmaceutical Ltd. China (a company of Johnson & Johnson).Trial registrationClinicalTrials.gov identifier, NCT01751867.

Project description:BackgroundThe molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are unclear.MethodsWe enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses. Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles. We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients. An extension cohort included 32 additional patients who received decitabine in different protocols.ResultsOf the 116 patients, 53 (46%) had bone marrow blast clearance (<5% blasts). Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile (29 of 43 patients [67%] vs. 24 of 71 patients [34%], P<0.001) and among patients with TP53 mutations than among patients with wild-type TP53 (21 of 21 [100%] vs. 32 of 78 [41%], P<0.001). Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes. However, in this study of 10-day courses of decitabine, neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles.ConclusionsPatients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk, TP53 mutations, or both had favorable clinical responses and robust (but incomplete) mutation clearance after receiving serial 10-day courses of decitabine. Although these responses were not durable, they resulted in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT01687400 .).

Dataset Information

Decitabine in patients with myelodysplastic syndromes: A multi-center, open-label, dose comparison trial.

Background

Methods

Results

Conclusion

Publications

Decitabine in patients with myelodysplastic syndromes: A multi-center, open-label, dose comparison trial.

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