Benefits of hypomethylating therapy in IPSS lower-risk myelodysplastic syndrome patients: A retrospective multicenter case series study

Lee, Je‐Hwan; Kim, Yoo-Jin; Sohn, Sang Kyun; Yoon, Sung‐Soo; Kim, Hawk; Cheong, June‐Won; Lee, Won-Sik; Lee, Gyeong‐Won; Lim, Sung-Nam; Kim, Min Kyoung; Lee, Ho Sup; Kim, Hyeoung-Joon

doi:10.1016/j.leukres.2017.08.004

Cited by 8 publications

(15 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pooled analyses also showed that decitabine might be significantly more beneficial than azacitidine with respect to ORR (59.5% vs 47.5%; P < 0.001). OS and EFS were comparable in the decitabine-and azacitidine-treated groups, and this finding was consistent with that of previous studies comparing these two HMAs [17][18][19][20] .…”

Section: Discussionsupporting

confidence: 92%

“…We performed a meta-analysis using previously published data and data from our patient cohort with lower-risk MDS. For the comparison of ORR between decitabine and azacitidine, one randomised study 21 , two retrospective studies 19,20 , and our study were included (Fig. 4a).…”

Section: Meta-analysismentioning

confidence: 99%

“…The sensitivity analysis of the above studies excluding our study also showed that ORR was significantly higher in patients treated with decitabine compared to azacitidine (odds ratio, 1.809; 95% CI, 1.023-3.199; P = 0.042; three studies, random effect model). In the analysis of ORR for decitabine treatment, one randomised study 21 , three non-randomised prospective studies 10,12,13 , two retrospective studies 19,20 providing available information on lower-risk MDS (low or intermediate-1 based on IPSS), and our study were included (Fig. 4b).…”

Section: Meta-analysismentioning

confidence: 99%

“…Decitabine had an estimated pooled ORR of 59.5% based on a fixed effects model. In the analysis of ORR for azacitidine, one randomised study 21 , one non-randomised prospective study 15 , four retrospective studies 14,16,19,20 providing available information on lower-risk MDS, and our study were included (Fig. 4c).…”

Section: Meta-analysismentioning

confidence: 99%

See 3 more Smart Citations

Comparison between 5-day decitabine and 7-day azacitidine for lower-risk myelodysplastic syndromes with poor prognostic features: a retrospective multicentre cohort study

Lee

Kang

Jeon

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Numerous studies have analysed the clinical efficacies of hypomethylating agents (HMAs) in patients with myelodysplastic syndromes (MDS). However, reports that compare the two HMAs, decitabine and azacitidine, in patients with lower-risk (low and intermediate-1) MDS are limited. We compared 5-day decitabine and 7-day azacitidine regimens in terms of treatment responses, survival outcomes, and adverse events in patients with lower-risk MDS with poor prognostic features. The overall response rates (ORRs) were 67.2% and 44.0% in the patients treated with decitabine and azacitidine, respectively (P = 0.014). While the median progression-free survival (PFS) was significantly better in the patients treated with decitabine than in those treated with azacitidine (P = 0.019), no significant differences in event-free and overall survival rates were observed between the two groups. Multivariate analysis revealed that compared with azacitidine treatment, decitabine treatment is significantly associated with a higher ORR (P = 0.026) and longer PFS (P = 0.037). No significant differences were observed in the incidence of grade 3 or higher haematologic adverse events in response to the two HMAs. In conclusion, in lower-risk MDS, especially with poor prognostic features, ORR and PFS were significantly better with 5-day decitabine treatment than with 7-day azacitidine treatment, with comparable safety. Myelodysplastic syndromes (MDS) are clonal haematologic disorders characterised by ineffective and dysplastic haematopoiesis that causes cytopenia, leading to the development of acute leukaemia 1,2. Previously, MDS was generally divided into lower-risk (low and intermediate-1) and higher-risk (intermediate-2 and higher) categories on the basis of the International Prognostic Scoring System (IPSS) 3 , and treatment decisions were usually made based on the risk group. The treatment for higher-risk MDS aims to modify the natural course of the disease using hypomethylating agents (HMAs), chemotherapy, or stem cell transplantation, whereas the treatment for lower-risk MDS aims to improve cytopenia, reduce transfusion requirements, and provide the best supportive care 4. However, lower-risk MDS patients with poor prognostic features were known to be associated with progression to acute myeloid leukaemia or severe cytopenia 4. Hence, more active treatments are needed for this group of patients. Currently, two types of HMAs (decitabine or azacitidine) are available for the treatment of MDS 5. Several previous studies reported the efficacy of HMAs in different clinical settings. In higher-risk MDS, a 7-day azacitidine regimen (75 mg/m 2 daily every 4 weeks) was reported to result in higher response rates and better overall survival

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Meta-analysismentioning

confidence: 99%

Section: Meta-analysismentioning

confidence: 99%

Section: Meta-analysismentioning

confidence: 99%

See 2 more Smart Citations

Comparison between 5-day decitabine and 7-day azacitidine for lower-risk myelodysplastic syndromes with poor prognostic features: a retrospective multicentre cohort study

Lee

Kang

Jeon

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Furthermore, response rates to AZA‐5 were hardly affected by poor karyotypes based on IPSS (Good vs Int + Poor, P = .1602) or IPSS‐R (Good vs Int + Poor + Very Poor, P = .2588). These results indicate that AZA‐7 is superior to AZA‐5 in lower‐risk MDS with poor karyotype based on IPSS or IPSS‐R…”

Section: Discussionmentioning

confidence: 77%

Five‐day regimen of azacitidine for lower‐risk myelodysplastic syndromes (refractory anemia or refractory anemia with ringed sideroblasts): A prospective single‐arm phase 2 trial

et al. 2018

View full text Add to dashboard Cite

Although azacitidine is the first‐line drug for higher‐risk myelodysplastic syndrome (MDS) patients, its efficacy for lower‐risk MDS remains unestablished. Therefore, we conducted a prospective study to examine the efficacy and safety of a 5‐day regimen of azacitidine (AZA‐5) for lower‐risk MDS. The primary endpoint was hematological improvement (HI) after 4 courses of therapy. A total of 51 patients with lower‐risk MDS based on the French‐American‐British (FAB) classification (44 patients with refractory anemia [RA] and 7 patients with refractory anemia with ringed sideroblasts [RARS]) were enrolled from 6 centers in Japan. The median age was 75 years (range: 51‐88). These patients received AZA‐5 (75 mg/m2; once daily for 5 sequential days). The median number of AZA‐5 courses was 8 (range: 1‐57), and 45 patients (88.2%) received more than 4 courses. HI and transfusion independency were seen in 24 patients (47.1%) and 11 patients (39.2%), respectively. A total of 11 patients (21.6%) achieved complete remission or marrow remission. WT1 mRNA levels were not significantly correlated with therapy response. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 26 (51.0%) and 11 (21.5%) patients, respectively. Nonhematological grade 3 or 4 adverse events were observed in 9 patients (17.6%). Together, these results indicate that AZA‐5 is feasible and effective for lower‐risk MDS patients as well as for higher‐risk MDS patients.

show abstract

Five‐day versus 7‐day treatment regimen with azacitidine in lower risk myelodysplastic syndrome: A phase 2, multicenter, randomized trial

Park

Lee

et al. 2022

Cancer

View full text Add to dashboard Cite

Background Low‐dose azacitidine (AZA) regimens, primarily 5‐day AZA, have been used in lower risk myelodysplastic syndrome (LrMDS) but they have yet to be directly compared to the standard 7‐day, uninterrupted dosing schedule. Method In this phase 2, multicenter, randomized trial, 55 patients with adult LrMDS (low and intermediate‐1 risk by international prognostic scoring system [IPSS]) were randomly assigned and received either 5‐day (n = 26) or 7‐day (n = 29) AZA between March 2012 and August 2020. The trial was stopped prematurely because of the slow accrual of patients. The primary end point was the overall response rate (ORR) of the 5‐day AZA as compared to that of the 7‐day regimen. Results Median patient age was 59 years, and IPSS intermediate‐1 risk comprised the majority (81.8%). The median number of cycles in both arms was six. In the ITT subset (n = 53), in each of the 5‐day and 7‐day arms, the ORR of 48.0% and 39.3%, hematologic improvement of 44.0% and 39.3%, and RBC transfusion independence of 35.3% and 40.0% were observed respectively, and none of these findings were significantly different between the two arms. A cytogenetic response rate was significantly higher in the 7‐day arm (8.3% and 53.8%, p = .027). Survival and adverse events were similar between the groups, although gastrointestinal toxicities, grade ≥3 thrombocytopenia, and febrile neutropenia were less frequent in the 5‐day arm. Conclusion The 5‐day AZA in LrMDS showed comparable efficacy to a 7‐day regimen in terms of similar overall response and other outcomes, despite significantly higher rates of cytogenetic responses in the 7‐day regimen. Lay summary Azacitidine (75 mg/m2/day for 7 consecutive days per 28‐day cycle) has shown survival benefit in patients with higher risk myelodysplastic syndrome (MDS). Although the use of azacitidine is less‐well studied for lower risk MDS, it is generally accepted as a feasible option for lower risk MDS (LrMDS).

show abstract

Benefits of hypomethylating therapy in IPSS lower-risk myelodysplastic syndrome patients: A retrospective multicenter case series study

Cited by 8 publications

References 23 publications

Comparison between 5-day decitabine and 7-day azacitidine for lower-risk myelodysplastic syndromes with poor prognostic features: a retrospective multicentre cohort study

Comparison between 5-day decitabine and 7-day azacitidine for lower-risk myelodysplastic syndromes with poor prognostic features: a retrospective multicentre cohort study

Five‐day regimen of azacitidine for lower‐risk myelodysplastic syndromes (refractory anemia or refractory anemia with ringed sideroblasts): A prospective single‐arm phase 2 trial

Five‐day versus 7‐day treatment regimen with azacitidine in lower risk myelodysplastic syndrome: A phase 2, multicenter, randomized trial

Contact Info

Product

Resources

About