Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome

Kantarjian, Hagop M.; O’Brien, Susan; Shan, Jianqin; Aribi, Ahmed; Garcia-Manero, G.; Jabbour, Elias; Ravandi, Farhad; Cortés, Jorge E.; Davisson, Jan; Issa, Jean–Pierre J.

doi:10.1002/cncr.22376

Cited by 102 publications

(66 citation statements)

References 63 publications

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“…2 Overall survival of responders and non-responders survival, respectively; P=.047) as well as a favorable response duration of 64 weeks. The observed median overall survival of 74 weeks in the group of responding patients corresponds well with the survival rates from the randomized phase II/III trials published for 5-AZA as well as decitabine [8,10,13,14,19], most of which had a higher number of treatment cycles. Therefore, our results suggest that even a limited number of treatment cycles may be beneficial for patients.…”

Section: Discussionsupporting

confidence: 82%

“…For responding patients, the median time to AML progression was 45 weeks (95% CI 22-68), while the median time to AML in non-responders was 14 weeks (95% CI [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. This difference was significant (P=0.038).…”

Section: Time To Aml and Overall Survivalmentioning

confidence: 99%

“…Several randomized trials with either 5-AZA or decitabine in patients with MDS have shown an overall response rate between 40% and 60%, an improved quality of life, a reduced risk of transformation to AML, and a trend toward longer overall survival compared to best supportive care [8][9][10][11][12][13][14]. In these trials, treatment was continued indefinitely until disease progression occurred.…”

Section: Introductionmentioning

confidence: 99%

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A limited number of 5-azacitidine cycles can be effective treatment in MDS

et al. 2008

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International audienceHypomethylating agents, such as 5-azacitidine (5-AZA) and 5-aza-2'-deoxycytidine (decitabine), have recently been approved for the treatment of myelodysplastic syndromes (MDS). Several randomized trials have shown favorable results concerning response rate, survival, transformation to acute leukemia, and quality of life. In these trials, treatment was administered continuously until progression. In the retrospective study presented here, we evaluated the outcome of patients with higher risk MDS or secondary acute myeloid leukemia (sAML) treated with a limited number of 5-AZA cycles. A total of 32 patients received 5-AZA alone ( = 30) or in combination with valproic acid and all-trans retinoic acid ( = 2). 5-AZA was administered subcutaneously at a fixed dose of 75 mg/m daily for 7 days and repeated every 28 days. 5-AZA was given for a median of four courses. Treatment was continued for two more cycles as consolidation in patients who had achieved complete remission (CR), marrow CR, or stable disease with hematologic improvement. The overall response rate was 50% according to the modified International Working Group criteria. Complete remissions were achieved in 15.6% and stable disease in 34.4% of patients. Peripheral blood counts normalized in 6.3% of patients while hematologic improvement was achieved in 25%. The median time to AML in responding patients was 45 weeks, while AML occurred after a median of 14 weeks in non-responding patients ( = .038). The median survival of all patients was 60 weeks; the median survival of responders was 74 weeks compared with 26 weeks in non-responders ( = .047). In this retrospective analysis, 5-AZA was associated with a survival advantage in responding patients with higher risk MDS or sAML. These favorable results suggest that patients may benefit even from a limited number of courses of 5-AZA. A randomized controlled clinical trial is required to prospectively validate these findings

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Section: Discussionsupporting

confidence: 82%

Section: Time To Aml and Overall Survivalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A limited number of 5-azacitidine cycles can be effective treatment in MDS

et al. 2008

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“…The multivariate analysis predicted shorter response duration and OS in the presence of a complex karyotype at baseline [4]. Our results are indeed similar to previous data by the MDACC (MD Anderson Cancer Center), who reported that chromosome 5 and 7 abnormalities were associated to shorter survival but not to the achievement of best response [5]. This patient group was similar, in terms of frequency of high-risk cytogenetic abnormalities (26%) and OS (median 20 months) to the series of patients enrolled in the AZA001 trial (high-risk cytogenetic abnormalities: 28% and median OS 24.4 months) [2].…”

supporting

confidence: 90%

Real‐life experience with azacitidine in myelodysplastic syndromes according to IPSS cytogenetic profile

et al. 2014

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agents became the mainstay of therapy for myelodysplastic syndromes (MDS) patients with bad prognostic features, treatment was usually support for older patients, and chemotherapy followed by transplant procedures for younger patients [1]. Rates of response and overall survival (OS) were low, even though patients were selected to receive intensive chemotherapy. The introduction of azacitidine changed therapeutic strategies and allowed treatment also of elderly patients. The AZA-001 trial, an international randomized phase III study of azacitidine (75 mg/m 2 /day for 7 days every 28-day), compared the drug with the three most common conventional regimens (CCR, i.e., best supportive care, low-dose cytarabine, and intensive chemotherapy) in IPSS (International Prognostic Scoring System) intermediate-2-and high-risk MDS [2]. Treatment was chosen according to physician preselection, based on age, comorbidities, performance status, and patient preferences. After a median follow up of 21 months, median OS was significantly longer in the azacitidine arm compared with the combined CCR group (24.5 vs 15 months, respectively) and 2-year OS was also significantly longer for azacitidine (50.8 vs 26.2%).OS was superior with azacitidine independently from IPSS cytogenetic subgroups: in particular, in patients with 27/del (7q), median OS was 13 months compared to 4.6 months for patients included in the CCR cohort [2].Aim of our study was to assess azacitidine efficacy according to cytogenetic risk at baseline in a large group of intermediate/high-risk MDS patients treated outside clinical trials. One hundred and sixty-six patients with primary or secondary MDS [chronic myelomonocytic leukemia (CMML) were excluded] were diagnosed and treated with azacitidine at six different Italian hematology units. Patients were recruited consecutively, based on physician's perspective and decision. All patients received azacitidine at the dose of 75 mg/mq with a schedule of 5 1 2 1 2 or of 7 consecutive days every 28 days, until disease progression or unacceptable toxicity. For all patients, clinical parameters such as age, sex, WHO classification, IPSS, and baseline cytogenetic evaluation were retrospectively collected. Responses were evaluated according to 2006 IWG criteria in an intention to treat basis [3]. Of 166 patients recruited, 103 were males and 63 females; median age was 69.5 years (range 49-89). A median of eight cycles was performed (range 1-60). According to IPSS stratification, there were 29 patients with intermediate-1 risk, 118 patients with intermediate-2, and 15 with high-risk MDS (seven patients not determined). According to the WHO classification, 37 patients were diagnosed as having RAEB-1, 101 patients as RAEB-2, and 28 patients as RCMD. According to IPSS cytogenetic risk stratification, 88 patients were in the good risk, 22 patients were in the intermediate risk, and 39 in the poor risk. The most frequent cytogenetic aberration, aside normal karyotype (48%), was 27 or del(7q) as isolated aberration in 9.4% of patients...

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“…Using a modification of an initial decitabine dosing regimen, two non-randomized studies in lower and higher and lower risk patients have demonstrated similar responses and survival duration to those with azaC (Kantarjian et al, 2007b;Steensma et al, 2009). The former single centre trial with 85% either higher risk or secondary MDS patients had an overall survival of 20 months, with a 2-year survival of 41%.…”

Section: Management Of Higher Risk Diseasementioning

confidence: 99%

Current therapeutic approaches for patients with myelodysplastic syndromes

Greenberg

2010

Br J Haematol

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SummaryThe myelodysplastic syndromes (MDS) are a heterogeneous spectrum of disorders requiring selective therapy based on patients' specific clinical features, predominantly their prognostic subgroups, age and performance status. Guidelines for management of patients with MDS have been generated by a number of national panels. This review focuses on evidencebased data supporting therapeutic approaches, which have also been recommended by the US National Comprehensive Cancer Network MDS Panel, with discussion of accessibility of recommended drugs in the US and in other countries. For lower risk disease (International Prognostic Scoring System Low and Intermediate-1) therapy is aimed at haematological improvement whereas for higher risk disease (Intermediate-2 and High) treatment focuses on altering disease natural history. Recent information regarding additional clinical and biological features has provided useful parameters for assessing disease prognosis that aid risk-based management decisions. The rationale for use of low versus high intensity therapies with these agents, including allogeneic haematopoietic stem cell transplantation, is discussed in detail.

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Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome

Cited by 102 publications

References 63 publications

A limited number of 5-azacitidine cycles can be effective treatment in MDS

A limited number of 5-azacitidine cycles can be effective treatment in MDS

Real‐life experience with azacitidine in myelodysplastic syndromes according to IPSS cytogenetic profile

Current therapeutic approaches for patients with myelodysplastic syndromes

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