Poor Outcome of Patients With Myelodysplastic Syndrome After Azacitidine Treatment Failure

Duong, Vu H.; Lin, Karen; Reljic, Tea; Kumar, Amit; Ali, Najla H Al; Lancet, Jeffrey E.; List, Alan F.; Komrokji, Rami S.

doi:10.1016/j.clml.2013.07.007

Cited by 46 publications

(42 citation statements)

References 18 publications

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“…However, this agent does not provide any curative effects, and transformation of CMML into acute myeloid leukemia (AML) continues to represent a frequent occurrence and a challenging treatment concern. Indeed, several studies have reported a poor outcome of AML arising from MDS/CMML after azacitidine failure [4,5,6] as well as treatment interruption due to clinical complications other than disease progression or the ineffectiveness of this agent [7]. AML transformation may occur in MDS/CMML patients unresponsive to azacitidine (primary failure) as well as in those who previously achieved a clinical response to this agent (secondary failure).…”

Section: Tablementioning

confidence: 99%

“…Moreover, very few and selected patients are suitable for allogeneic stem cell transplantation (SCT), which represents the only true salvage treatment in this difficult setting [8]. Thus far, the severity and extent of this challenging disorder has been strongly emphasized by the proposal to consider AML arising from MDS after the failure of hypomethylating agents as an emerging entity with poor outcome for which new and effective treatments are urgently needed [5]. In order to describe our real-life experience in this setting, we retrieved the data of 26 patients (8 female) with a median age of 72 (32-82) years from our MDS/CMML database (table 1).…”

Section: Tablementioning

confidence: 99%

“…AML transformation may occur in MDS/CMML patients unresponsive to azacitidine (primary failure) as well as in those who previously achieved a clinical response to this agent (secondary failure). The clinical presentation of AML in azacitidine-failed MDS/CMML patients may be rapidly aggressive [5,6], and outcome of the affected patients is particularly poor, with a reported median survival of 21 weeks and 1- and 2-year survival rates of 19 and 8%, respectively [5], since virtually no suitable therapeutic options other than investigational agents are nowadays available [8]. Moreover, very few and selected patients are suitable for allogeneic stem cell transplantation (SCT), which represents the only true salvage treatment in this difficult setting [8].…”

Section: Tablementioning

confidence: 99%

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Dismal Outcome of Acute Myeloid Leukemia Secondary to Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia after Azacitidine Failure in a Daily-Life Setting

Niscola

Tendas²,

Cupelli³

et al. 2014

Acta Haematol

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Section: Tablementioning

confidence: 99%

Section: Tablementioning

confidence: 99%

Section: Tablementioning

confidence: 99%

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Dismal Outcome of Acute Myeloid Leukemia Secondary to Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia after Azacitidine Failure in a Daily-Life Setting

Niscola

Tendas²,

Cupelli³

et al. 2014

Acta Haematol

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“…If response is achieved, azacitidine is typically continued until disease progression, unacceptable toxicity, or definitive therapy with SCT. If no response is achieved after six cycles of azacitidine, then prognosis is generally poor [48,49]. Small case series have shown that decitabine treatment after azacitidine failure yields modest responses (ORR: 0%-28%) that are generally short lived [48,[50][51][52][53]; however, this is not currently standard treatment practice.…”

Section: Azacitidine For Injectionmentioning

confidence: 99%

“…Small case series have shown that decitabine treatment after azacitidine failure yields modest responses (ORR: 0%-28%) that are generally short lived [48,[50][51][52][53]; however, this is not currently standard treatment practice. The current standard of care for patients with MDS who have not responded after at least six cycles of azacitidine treatment is to consider clinical trials [48,49] or proceed with SCT [51].…”

Section: Azacitidine For Injectionmentioning

confidence: 99%

Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia

Cogle

Scott

Boyd³

2015

The Oncologist

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The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal myeloid malignancies characterized by multilineage cytopenias, recurrent cytogenetic abnormalities, and risk of progression to acute myeloid leukemia (AML). AML, which can occur de novo as well as secondary to MDS, is characterized by malignant clones of myeloid lineage in the bone marrow and peripheral blood, with dissemination into tissues. The cytidine nucleoside analog and epigenetic modifier azacitidine is approved in the U.S. for the treatment of all French-American-British subtypes of MDS and in many countries for the treatment of AML with 20%-30% blasts and multilineage dysplasia according to the World Health Organization classification. Benefits of azacitidine treatment of patients with AML with .30% blasts have also been shown in a recent phase III trial. Oral administration of azacitidine may enhance patient convenience, eliminate injection-site reactions, allow for alternative dosing and scheduling, and enable long-term treatment. Phase I studies with oral azacitidine (CC-486) have shown biological activity, clinical responses, and tolerability in patients with MDS and AML. Extended dosing schedules of oral azacitidine (for 14 or 21 days of 28-day cycles) are currently under investigation as frontline therapy in patients with lower risk MDS, as maintenance therapy for patients with AML not eligible for stem cell transplant, and as maintenance therapy for patients with MDS or AML following stem cell transplant. This review presents clinical data supporting the use of injectable azacitidine in MDS and AML and examines the rationale for and results of the clinical development of oral azacitidine.

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Phase II clinical study of erlotinib for treatment of myelodysplastic syndromes

Komrokji

Padron

et al. 2014

American J Hematol

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Outcome in patients with myelodysplastic syndrome (MDS) after azanucleoside failure is poor with unmet need for active novel agents. Preclinical data have suggested that erlotinib has in vivo and in vitro off epidermal growth factor receptor (EGFR)-target activity in MDS. We conducted a phase II study with single-agent erlotinib 150 mg/day orally in MDS patients following azanucleoside failure. All intermediate-2 or high-risk MDS patients by International Prognostic Scoring System and only those low/intermediate-1 patients with transfusion-dependent anemia or platelet counts <50 × 109/L or a significant clinical hemorrhage requiring platelet transfusion or ANC <1 × 109/L were eligible, with most of our patients being at high risk. In 35 eligible patients, overall best response was 14% (3 patients having marrow complete response and 2 hematological improvement). Four deaths occurred on study (sepsis, intracranial hemorrhage, sudden death, and acute myeloid leukemia (AML)). The most common observed grade 3/4 toxicities according to CTCAE v3 were diarrhea (17.1%), rash (17.1%), and infection (11.6%), accompanied by fatigue, thrombocytopenia, and anorexia at 5.7% each. Median overall survival was 6.8 months (95% CI 4.9–13.2), and leukemia-free survival was 5 months (95% CI 3.4–7.3). Erlotinib was generally well tolerated, with modest single-agent activity. Given these results and preclinical data suggesting synergistic effect with azanucleosides, the combination should be further explored.

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Poor Outcome of Patients With Myelodysplastic Syndrome After Azacitidine Treatment Failure

Cited by 46 publications

References 18 publications

Dismal Outcome of Acute Myeloid Leukemia Secondary to Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia after Azacitidine Failure in a Daily-Life Setting

Dismal Outcome of Acute Myeloid Leukemia Secondary to Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia after Azacitidine Failure in a Daily-Life Setting

Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia

Phase II clinical study of erlotinib for treatment of myelodysplastic syndromes

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