Further Analysis of Trials With Azacitidine in Patients With Myelodysplastic Syndrome: Studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B

Silverman, Lewis R.; McKenzie, David R.; Peterson, Bercedis L.; Holland, James F.; Backstrom, Jay T.; Beach, C. L.; Larson, Richard A.

doi:10.1200/jco.2005.05.4346

Cited by 525 publications

(431 citation statements)

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“…was observed in patients who were transfusion independent at baseline. In our cohort of patients with lower risk MDS, similar to what was observed in Cancer and Leukemia Group B (CALGB) Trial 9221, 34,35 which used FAB classification, the survival of patients in higher risk categories, as defined by the MDACC score, and, perhaps more noteworthy, the survival of patients in the ''very-high-risk'' category (according to the dynamic WPSS score, which permits evaluation and allows reassessment of prognosis for patients with MDS during the course of the disease) remained poorer than the survival reported in the other MDS subsets despite treatment with azacitidine. Indeed, because this was a nonrandomized, retrospective study without a control arm, we hesitate to draw conclusions about the impact of azacitidine on the OS of any single subgroup.…”

Section: Discussionsupporting

confidence: 79%

“…No specific information on the outcomes of 11 patients who had refractory anemia or refractory anemia with ringed sideroblasts from another CALGB study (the 8921 protocol) were given. 32 A reanalysis of these trials did not produce further detailed data on patients with lower risk MDS. 35 More recently, in a US community-based, multicenter patient registry study (AVIDA; currently only published in abstract form), 52 MDS patients with IPSS classified as low risk or Int-1 risk received a median of 3 cycles of azacitidine.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with higher risk MDS, azacitidine reduces transfusion dependence, delays transformation to AML, and improves quality of life. [31][32][33][34][35] Recent data also have demonstrated that azacitidine is the first agent to induce a significant survival advantage compared with conventional care regimens in patients with higher risk MDS. 36 Most previous studies of azacitidine in patients with MDS, however, included only a very small proportion of those with lower risk disease, and a specific analysis of response rates and survival based on IPSS criteria was never performed exclusively on this population of patients.…”

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confidence: 99%

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Azacitidine for the treatment of lower risk myelodysplastic syndromes

Musto

Maurillo

Spagnoli

et al. 2010

Cancer

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BACKGROUND:Azacitidine induces responses and prolongs overall survival compared with conventional care regimens in patients who have high‐risk myelodysplastic syndromes (MDS). However, limited data are available concerning the efficacy and safety of azacitidine in patients who have lower risk MDS.METHODS:The authors retrospectively evaluated 74 patients with International Prognostic Scoring System low‐risk or intermediate 1‐risk MDS, who received azacitidine on a national named patient program. At baseline, 84% of patients were transfusion‐dependent, 57% had received erythropoietin, and 51% were aged >70 years. Azacitidine was administered subcutaneously for 5 days (n = 29 patients), 7 days (n = 43 patients), or 10 days (n = 2 patients) every month at a dose of 75 mg/m2 daily (n = 45 patients) or at a fixed dose of 100 mg daily (n = 29 patients) and for a median of 7 cycles (range, 1‐30 cycles).RESULTS:According to the 2006 International Working Group criteria, overall response rate (ORR) was 45.9%, including complete responses (10.8%), partial responses (9.5%), hematologic improvements (20.3%), and bone marrow complete responses (5.4%). The ORR was 51.6% in 64 patients who completed ≥4 cycles of treatment. The median duration of response was 6 months (range, 1‐30 months). After a median follow‐up of 15 months, 71% of patients remained alive. A survival benefit was observed in responders versus nonresponders (94% vs 54% of patients projected to be alive at 2.5 years, respectively; P < .0014). The most common grade 3 or 4 adverse events were myelosuppression (21.6%) and infection (6.8%).CONCLUSIONS:The current results indicated that azacitidine may be a feasible and effective treatment for patients with lower risk MDS. Cancer 2010. © 2010 American Cancer Society.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Azacitidine for the treatment of lower risk myelodysplastic syndromes

Musto

Maurillo

Spagnoli

et al. 2010

Cancer

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“…Indeed, Azacitidine (AZA) has demonstrated a survival benefit over conventional care regimens [best supportive care (BSC), low-dose cytarabine, or intensive chemotherapy] in higher risk MDS (including AML with 20 to 30% blasts) and has become the standard of care in MDS patients not eligible for allogeneic stem cell transplantation (allo-SCT) [17,18]. Note worthily, AZA can trigger responses in patients with poor chances of response to conventional treatment as patients with monosomy 7 [19].…”

Section: Introductionmentioning

confidence: 99%

Azacitidine treatment for patients with myelodysplastic syndrome and acute myeloid leukemia with chromosome 3q abnormalities

et al. 2015

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Acute Myeloid Leukemia (AML) and myelodysplasia (MDS) with chromosome 3q abnormalities have a dismal outcome either untreated or with conventional treatments. Azacitidine (AZA) is now considered as the standard of care in high-risk MDS and oligoblastic AML patients. The objective of this study was to evaluate the impact of azacitine treatment in this cytogenetic subgroup. We report here a multicentre retrospective study of 157 patients treated with AZA for AML/MDS with chromosome 3q abnormalities and 27 patients with isolated EVI-1 overexpression. Median age was 65 years, 40 patients (25%) had inv(3)(q21q26.2) or t(3;3)(q21;q26.2), 36 patients (23%) had other balanced 3q26 rearrangements, 8 patients (5%) had balanced 3q21 rearrangements and 73 patients (46%) had other 3q abnormalities. The overall response rate was 50% (29% CR). Median overall survival was 10.6 months. By multivariate analysis, patients with lower bone marrow blast counts, higher platelet counts, non-complex cytogenetics, and absence of prior treatment with intensive chemotherapy had a better outcome. 27 patients were allo-transplanted and achieved a 21-month median OS. Balanced 3q21 translocations were associated with a better response rate and overall survival. Outcome of patients with isolated EVI-1 overexpression was comparable to that of patients with chromosome 3q lesions. Thus, AML/MDS patients with 3q abnormalities appear to be a heterogeneous group in their response to AZA, and AZA may represent a suitable option in particular as a bridge to allogeneic transplantation.

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“…Fenaux et al observed that older patients with MDS (FAB) and 20-30 % BM blasts who received azacitidine had longer OS than those receiving BSC only [6]. Such an effect of azacitidine had been also suggested in a previous pooled analysis of various studies [14]. A comparable effect of decitabine in this patient group has not yet been established.…”

Section: Survival In Subgroups Of Raebt Patientsmentioning

confidence: 96%

Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG)

et al. 2015

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In the European Organisation for Research and Treatment of Cancer (EORTC)/GMDSSG phase III trial 06011, we compared decitabine (15 mg/m 2 every 8 h for 3 days) with best supportive care (BSC) in patients ≥60 years with myelodysplastic syndromes (MDS) by FrenchAmerican-British (FAB) criteria. Here, we reinvestigate trial 06011 for the activity and efficacy specifically in patients with refractory anemia with excess blasts in transformation (RAEBt). Response rates in the decitabine arm (N=40) were as follows: complete or partial remission, 15 %; hematologic improvement, 15 %; resistant disease, 30 %. RAEBt patients in the decitabine arm had longer progression-free survival (PFS; hazard ratio (HR) 0.30, 95 % confidence interval (CI) 0.18-0.51; median, 6.2 vs 2.8 months) and overall survival (OS; HR 0.68, 95 % CI 0.42-1.11; median, 8.0 vs 6.0 months) than in the BSC arm (N=35). Censoring at allogeneic hematopoietic stem cell transplantation, the OS difference between the treatment groups increased, particularly among patients Electronic supplementary material The online version of this article (doi:10.1007/s00277-015-2489-6) contains supplementary material, which is available to authorized users.

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Further Analysis of Trials With Azacitidine in Patients With Myelodysplastic Syndrome: Studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B

Abstract: Azacitidine provides important clinical benefits for patients with high-risk MDS.

Cited by 525 publications

References 10 publications

Azacitidine for the treatment of lower risk myelodysplastic syndromes

Azacitidine for the treatment of lower risk myelodysplastic syndromes

Azacitidine treatment for patients with myelodysplastic syndrome and acute myeloid leukemia with chromosome 3q abnormalities

Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG)

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