Novel therapies for myelodysplastic syndromes

Faderl, Stefan; Kantarjian, Hagop M.

doi:10.1002/cncr.20381

Cited by 47 publications

(28 citation statements)

References 111 publications

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“…Because Thal and especially lenalidomide have been reported to exhibit clinical activity in patients diagnosed with myelodysplastic syndrome (MDS), 19,20 we examined whether there were differences in the development of MDS-associated cytogenetic abnormalities (MDS-CA) between the 2 study arms. 21 The 5-year cumulative frequency of MDS-CA was identical at 4% in both arms, indicating that Thal provided no protective effect against the development of therapy-related myelodysplastic syndrome (t-MDS).…”

Section: Implications Of Randomization To Thalidomide On Mri-defined mentioning

confidence: 99%

Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities

Barlogie

Pineda‐Roman

Rhee

et al. 2008

Blood

216

171

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Total Therapy 2 examined the clinical benefit of adding thalidomide up-front to a tandem transplant regimen for newly diagnosed patients with multiple myeloma. When initially reported with a median follow-up of 42 months, complete response rate and event-free survival were superior among the 323 patients randomized to thalidomide, whereas overall survival was indistinguishable from that of the 345 patients treated on the control arm. With further follow-up currently at a median of 72 months, survival plots segregated 5 years after initiation of therapy in favor of thalidomide (P ‫؍‬ .09), reaching statistical significance for the one third of patients exhibiting cytogenetic abnormalities (CAs; P ‫؍‬ .02), a wellrecognized adverse prognostic feature. The duration of complete remission was also superior in the cohort presenting with CAs such that, at 7 years from onset of complete remission, 45% remained relapse-free as opposed to 20% on the control arm (P ‫؍‬ .05). These observations were confirmed when examined by multivariate analysis demonstrating that thalidomide reduced the hazard of death by 41% among patients with CA-positive disease (P ‫؍‬ .008). Because two thirds of patients without CAs have remained alive at 7 years, the presently emerging separation in favor of thalidomide may eventually reach statistical significance as well. (Blood. 2008;112:3115-3121)

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Section: Implications Of Randomization To Thalidomide On Mri-defined mentioning

confidence: 99%

Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities

Barlogie

Pineda‐Roman

Rhee

et al. 2008

Blood

216

171

View full text Add to dashboard Cite

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“…[1][2][3][4] Older patients, which constitute the large majority, generally receive supportive care only, low-dose chemotherapy or investigational agents. The United States Food and Drug Administration (FDA) recently approved 5-azacytidine (Vidaza, Pharmion, Boulder, CO), lenalidomide (Revlimid, Celgene, Summit, NJ), and decitabine (Dacogen, MGI Pharma, Bloomington, MN; SuperGen, Dublin, CA; Johnson & Johnson Pharmaceutical Research and Development LLC, Raritan, NJ) as new therapeutic options for patients with MDS, but treatments with improved safety, especially those that target new disease-related growth pathways, are needed to improve patient outcomes.…”

Section: Introductionmentioning

confidence: 99%

A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome

Fenaux

Raza

Mufti

et al. 2007

Blood

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“…1,2 Several prognostic models, including the International Prognostic Scoring System (IPSS), have been proposed to account for the heterogeneity in MDS. [3][4][5] Prognostic factors include the percent of bone marrow blasts, cytogenetic abnormalities, the degree and number of cytopenias (according to the IPSS), and others.…”

mentioning

confidence: 99%

Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome

Kantarjian

O’Brien

Huang

et al. 2007

Cancer

Self Cite

166

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BACKGROUNDDecitabine, a hypomethylating agent, is active and has been approved for the treatment of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia. Intensive chemotherapy is an accepted form of therapy for patients with higher risk MDS. The comparative efficacy of these 2 forms of treatment in MDS is unknown. The objective of the current study was to compare the efficacy and toxicity profiles of decitabine and intensive chemotherapy in MDS.METHODSThe authors compared lower intensity decitabine therapy (n = 115 patients) with intensive chemotherapy (as it is used in acute myeloid leukemia [AML]) in patients with higher risk MDS. Two comparisons were made with a cohort of 376 historic patients (from 1995 to 2005): The first comparison included a subcohort of 115 patients (Group A) who matched the 115 decitabine study patients according to age, International Prognostic Scoring System, and cytogenetics; and the second comparison included the whole cohort of 376 patients without matching (Group B). A multivariate analysis was performed for outcome.RESULTSThe complete remission (CR) rate according to AML criteria was 43% with decitabine, 46% with intensive chemotherapy in Group A, and 52% with intensive chemotherapy in Group B. Compared with Group A, mortality at 6 weeks was 3% with decitabine versus 13% with intensive chemotherapy (P = .006) and, at 3 months, 7% with decitabine versus 23% with intensive chemotherapy (P = .001). Survival was better with decitabine versus intensive chemotherapy in Group A (median survival: 22 months vs 12 months; P < .001). A multivariate analysis of survival in all 491 patients who received decitabine or intensive chemotherapy (Group B) selected decitabine as an independent, favorable prognostic factor for survival (P = .006; hazard ratio, 0.74) after accounting for the independent prognostic effect of pretreatment factors.CONCLUSIONSIn this analysis, decitabine was associated with a survival advantage compared with intensive chemotherapy in patients with higher risk MDS. Future studies should evaluate prospectively the results of decitabine versus intensive chemotherapy in this setting. Cancer 2007 © 2007 American Cancer Society.

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Novel therapies for myelodysplastic syndromes

Cited by 47 publications

References 111 publications

Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities

Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities

A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome

Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome

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