P-159 Lenalidomide performance in the real world: Patterns of utilization and effectiveness in a Medicare population with myelodysplastic syndromes

Zeidan, Amer M.; Gore, S.D.; McNally, Diane; Hendrick, Franklin; Mahmoud, Dalia; Davidoff, A.

doi:10.1016/s0145-2126(13)70207-8

Cited by 4 publications

(4 citation statements)

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“…Another early phase study of sequential azacitidine–lenalidomide in HR-MDS and AML with del5q reported a lower ORR (26%) [41]. It is noteworthy that real-life analyses using US Medicare claims data of MDS patients showed that lenalidomide is frequently used in the community concurrently with other agents including erythropoiesis-stimulating agents (ESA) and azacitidine [43]. …”

Section: Combination Strategiesmentioning

confidence: 99%

Beyond hypomethylating agents failure in patients with myelodysplastic syndromes

Zeidan

Kharfan‐Dabaja

Komrokji

2014

Current Opinion in Hematology

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Purpose of review Although hypomethylating agents (HMAs) significantly improve outcomes in myelodysplastic syndromes (MDS), only half the patients achieve objective responses, and most responders lose response within 1–2 years. Azacitidine prolongs survival by a median of only 9.5 months. Failure of HMA therapy is associated with a very dismal prognosis. Therefore, novel therapeutic approaches are clearly needed. Recent findings The sequential use of the alternative HMA after failure of first line HMA is associated with modest efficacy. The improved understanding of the biologic underpinnings of the disease have opened the door to study investigational agents that target disrupted molecular pathways critical to the pathogenesis of MDS. Combination treatment strategies using an azacitidine backbone are demonstrating promising early results. Expanding the applicability of allogeneic stem cell transplantation (alloSCT), the only curative modality, by reducing toxicity and relapse rates is another area of active research. Summary Sequential switching to the alternative HMA, clinical trials of novel targeted therapies, azacitidine-based combination therapeutic strategies, and improvements in the alloSCT platform are the main directions in improving outcomes of MDS post HMA failure.

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Section: Combination Strategiesmentioning

confidence: 99%

Beyond hypomethylating agents failure in patients with myelodysplastic syndromes

Zeidan

Kharfan‐Dabaja

Komrokji

2014

Current Opinion in Hematology

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“…Lenalidomide is classically described as an immunomodulatory agent, but high impact discoveries continue to shed light on previously unrecognized aspects of the pleiotropic effects of the drug that appear to be disease-, karyotype-and potentially dosedependent in different settings (Zeidan et al, 2015b;Abou Zahr et al, 2016). In LR-MDS for example, lenalidomide has clear differential clinical activity with transfusion-independence rates of 56-67% and a median response duration of 2Á2 years among patients with del5q compared to 25% response rate and a median duration of 33-41 weeks among those without del5q (List et al, 2006(List et al, , 2014Raza et al, 2008;Fenaux et al, 2011;Zeidan et al, 2013b;Santini et al, 2016). Lenalidomide affects karyotype-dependent pathways by impacting haplosufficient genes in del5q patients such as the casein kinase 1a (CSNK1A1) while it exerts karyotype-independent pathways in non-del5q patients by potentially impacting immune function, microenvironment, erythroid differentiation genes, and angiogenesis (Kronke et al, 2015;Abou Zahr et al, 2016).…”

mentioning

confidence: 99%

A phase 2 trial of high dose lenalidomide in patients with relapsed/refractory higher‐risk myelodysplastic syndromes and acute myeloid leukaemia with trilineage dysplasia

et al. 2016

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Limited therapies exist for patients with refractory and relapsed (RR) higher-risk myelodysplastic syndromes (HR-MDS) and acute myeloid leukaemia with trilineage dysplasia (AML-TD). High dose (HD) lenalidomide (50 mg) has activity as frontline therapy in elderly AML but there is limited data in the RR setting. This phase II trial included patients with RR HR-MDS or AML-TD at 2 doses of lenalidomide (15 or 50 mg) on days 1-28 of 42-day cycles. The primary endpoint was response rate using the 2006 International Working Group criteria. Overall survival (OS) was estimated by Kaplan-Meier methods. Of 27 patients enrolled, 59% had HR-MDS and 31% AML-TD. No patient had isolated del5q; 41% had poor-risk karyotype. Of 9 patients treated at 15 mg, 56% completed ≥2 cycles with no responses. Of 18 patients treated at 50 mg, 39% completed ≥2 cycles and 11% responded but all experienced grade 3/4 neutropenic fever/infection. The 60-day mortality rate was 30%. Median OS was 114 days with 19% surviving ≥1 year. The study was terminated due to lack of robust clinical activity. In conclusion, lenalidomide at 15 mg is ineffective in RR myeloid malignancies. Continous high dosing schedules are poorly tolerated and minimally active. Further evaluation should be considered in upfront intensive chemotherapy-ineligible patients.

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“…Azacitidine‐based combination approaches (e.g. with lenalidomide) for MDS remain investigational (Zeidan et al , ,f). Baseline biomarkers or clinical variables that consistently predict clinical benefit from azacitidine therapy in patients with MDS have not been identified despite extensive investigation (Steensma, ).…”

Section: Discussionmentioning

confidence: 99%

Platelet count doubling after the first cycle of azacitidine therapy predicts eventual response and survival in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukaemia but does not add to prognostic utility of the revised IPSS

et al. 2014

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Summary Reliable clinical or molecular predictors of benefit from azacitidine therapy in patients with myelodysplastic syndromes (MDS) are not defined. Doubling of platelet count at start of second cycle of azacitidine therapy compared to baseline has been associated with achieving response and survival advantage in a Dutch cohort. To validate this observation, we analyzed a larger cohort of North American patients whose data was collected in a prospective clinical trial with a longer median follow-up. We found a significant association between platelet count doubling after first cycle of azacitidine therapy and probability of achieving objective response. Among patients with MDS or oligoblastic acute myeloid leukemia (<30% bone marrow blasts, n=102), there was a statistically significant reduction in risk of death for patients who achieved platelet count doubling (n=23, median OS, 21.0 months) compared to those who did not (n=79, median OS, 16.7 months, adjusted HR (no/yes)=1.88, 95% CI, 1.03-3.40, P=0.04). Nonetheless, the addition of this platelet count doubling variable did not improve the survival prediction provided by the revised International Prognostic Scoring System or the French Prognostic Scoring System. Identification of reliable and consistent predictors for clinical benefit for azacitidine therapy remains an unmet medical need and a top research priority.

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P-159 Lenalidomide performance in the real world: Patterns of utilization and effectiveness in a Medicare population with myelodysplastic syndromes

Cited by 4 publications

References 0 publications

Beyond hypomethylating agents failure in patients with myelodysplastic syndromes

Beyond hypomethylating agents failure in patients with myelodysplastic syndromes

A phase 2 trial of high dose lenalidomide in patients with relapsed/refractory higher‐risk myelodysplastic syndromes and acute myeloid leukaemia with trilineage dysplasia

Platelet count doubling after the first cycle of azacitidine therapy predicts eventual response and survival in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukaemia but does not add to prognostic utility of the revised IPSS

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