Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1–risk myelodysplastic syndromes with karyotypes other than deletion 5q

Raza, Azra; Reeves, James A.; Feldman, Eric J.; Dewald, Gordon W.; Bennett, John M.; Deeg, H. Joachim; Dreisbach, Luke; Schiffer, Charles A.; Stone, Richard; Greenberg, Peter L.; Curtin, Peter T.; Klimek, Virginia M.; Shammo, Jamile M.; Thomas, Deborah A.; Knight, Robert D.; Schmidt, M.; Wride, Kenton; Zeldis, Jerome B.; List, Alan F.

doi:10.1182/blood-2007-01-068833

Cited by 393 publications

(286 citation statements)

References 26 publications

Supporting

Mentioning

262

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, lower response rate in patients with longer duration of MDS has also been observed after treatment with lenalidomide or immunosuppressive therapy. [22][23] Taken together, these observations support the hypothesis that TNF-α blockade alone has insufficient activity in patients with MDS. The median progression-free survival from randomization was 0.6 (95% CI, 0.5-3.0) years in the 3 mg/kg arm versus 1.6 (0.4-3.4) years in the 5 mg/kg arm ( Figure 1A), while the median survival was 2.6 (1.9-not reached) years versus 3.4 (2.2-5.3) years in the 3 mg/kg and 5 mg/kg arms, respectively (Online Supplementary Figure 2A).…”

Section: Activity and Outcomesupporting

confidence: 74%

Value of infliximab (Remicade(R)) in patients with low-risk myelodysplastic syndrome: final results of a randomized phase II trial (EORTC trial 06023) of the EORTC Leukemia Group

Baron¹,

Suciu²,

Amadori³

et al. 2011

Haematologica

View full text Add to dashboard Cite

Section: Activity and Outcomesupporting

confidence: 74%

Value of infliximab (Remicade(R)) in patients with low-risk myelodysplastic syndrome: final results of a randomized phase II trial (EORTC trial 06023) of the EORTC Leukemia Group

Baron¹,

Suciu²,

Amadori³

et al. 2011

Haematologica

View full text Add to dashboard Cite

“…These trials included patients with the del(5q) cytogenetic abnormality with or without other cytogenetic abnormalities (MDS-003) 10 and patients without del(5q) (MDS-002). 21 Study eligibility as well as definition of TI as the primary end point have been reported previously and are summarized in the Appendix (online only). 10,21…”

Section: Journal Of Clinical Oncology O R I G I N a L R E P O R T V Omentioning

confidence: 99%

“…10 In a second multicenter phase II study (MDS-002) in which lenalidomide was administered to transfusion-dependent patients with MDS without the del(5q) cytogenetic abnormality, TI was achieved in 26% of patients, and the corresponding frequency of grade 3 or 4 cytopenias was lower, occurring in 25% to 30% of patients. 21 Given the concordance between suppression of the MDS clone and TI response in patients with the del(5q) abnormality, we investigated whether lenalidomide-induced cytopenias that occur early in the treatment course serve as a surrogate marker of clonal suppression and, therefore, may be predictive of TI response. We analyzed data from the MDS-002 and MDS-003 studies to determine the relationship between treatment-related cytopenias and response to lenalidomide.…”

Section: Journal Of Clinical Oncology O R I G I N a L R E P O R T V Omentioning

confidence: 99%

Relationship of Treatment-Related Cytopenias and Response to Lenalidomide in Patients With Lower-Risk Myelodysplastic Syndromes

Sekeres

Maciejewski

Giagounidis

et al. 2008

JCO

Self Cite

103

View full text Add to dashboard Cite

A B S T R A C T PurposePatients with myelodysplastic syndromes (MDS) often require treatment with growth factors (GFs) or non-GF therapies. One non-GF drug, lenalidomide, is particularly effective at achieving transfusion independence (TI) in patients with lower-risk MDS with the del(5q) cytogenetic abnormality. However, approximately half of del(5q) patients and one quarter of non-del(5q) patients treated with lenalidomide experience significant cytopenias. Lenalidomide-induced cytopenias occurring early in treatment may serve as a surrogate marker of clonal suppression and, therefore, may be predictive of a TI response. Patients and MethodsWe analyzed 362 low-risk, transfusion-dependent patients with MDS, with or without the del(5q) abnormality, enrolled in two phase II studies (MDS-003 and MDS-002) to determine whether treatment-related cytopenias are correlated with lenalidomide response. Cytopenias were assessed during the first 8 weeks of therapy, and response was defined as TI; response predictors were explored in univariate and multivariate analyses. ResultsAmong patients with del(5q), 70% of those whose platelet count decreased by Ն 50% achieved TI, as compared with 42% of those whose platelet count remained stable or declined by less than 50% (P ϭ .01). Among patients without baseline neutropenia, 82% of those whose absolute neutrophil count (ANC) decreased by Ն 75% achieved TI, as compared with 51% whose ANC remained stable or decreased by less than 75% (P ϭ .02). These relationships were consistent in multivariate analyses. No relationship between the development of cytopenias and response could be established for lower-risk patients with MDS without del(5q). ConclusionThese findings support the hypothesis that a direct cytotoxic effect of lenalidomide specific to the del(5q) clone may be indicative of a TI response.

show abstract

“…For patients with MDS, the IPSS provides an estimated evaluation of life expectancy and transformation to AML that can vary from a few months to several years, according to the level of risk. 1 Among the current therapeutic options available for patients with lower risk MDS, it has been established that erythropoiesis-stimulating agents (ESAs), [6][7][8][9][10][11][12] immunomodulatory drugs like thalidomide and lenalidomide, [13][14][15][16][17][18][19] and immunosuppressive therapies 20,21 can at least partially restore hematopoiesis and induce transfusion independence in selected patients. However, with the possible exception of younger patients who are candidates for allogeneic stem cell transplantation, [21][22][23] transfusions and chelating therapy remain widely used treatment options for a large number patients.…”

mentioning

confidence: 99%

Azacitidine for the treatment of lower risk myelodysplastic syndromes

Musto

Maurillo

Spagnoli

et al. 2010

Cancer

View full text Add to dashboard Cite

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.

show abstract

Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1–risk myelodysplastic syndromes with karyotypes other than deletion 5q

Cited by 393 publications

References 26 publications

Value of infliximab (Remicade(R)) in patients with low-risk myelodysplastic syndrome: final results of a randomized phase II trial (EORTC trial 06023) of the EORTC Leukemia Group

Value of infliximab (Remicade(R)) in patients with low-risk myelodysplastic syndrome: final results of a randomized phase II trial (EORTC trial 06023) of the EORTC Leukemia Group

Relationship of Treatment-Related Cytopenias and Response to Lenalidomide in Patients With Lower-Risk Myelodysplastic Syndromes

Azacitidine for the treatment of lower risk myelodysplastic syndromes

Contact Info

Product

Resources

About