Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents

Santini, Valeria; Almeida, António; Giagounidis, Aristoteles; Gröpper, Stefanie; Jonášová, Anna; Vey, Norbert; Mufti, Ghulam J.; Buckstein, Rena; Mittelman, Moshe; Platzbecker, Uwe; Shpilberg, Ofer; Ram, Ron; Cañizo, Consuelo del; Gattermann, Norbert; Ozawa, Keiya; Risueño, Alberto; MacBeth, Kyle J.; Zhong, Jianhua; Séguy, Francis; Hoenekopp, Albert; Beach, C.L.; Fenaux, Pierre

doi:10.1200/jco.2015.66.0118

Cited by 192 publications

(160 citation statements)

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“…4) they have not been translated into an actionable test, and have not been validated in non-del(5q) cases.(ref. 5) Recently, the mechanism of action of LEN has been attributed to induction of ubiquitination and enhanced degradation of casein kinase 1A1 (CK1α) by the E3 ubiquitin ligase cereblon.(ref. 6)…”

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confidence: 99%

Molecular predictors of response in patients with myeloid neoplasms treated with lenalidomide

et al. 2016

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confidence: 99%

Molecular predictors of response in patients with myeloid neoplasms treated with lenalidomide

et al. 2016

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“…49 Transfusion independence was obtained in 26.9% of the cases. A subgroup of patients with endogenous EPO levels ,100 U/L who had received previous ESA treatment, reached transfusion independence in 42.5% of the cases.…”

Section: Mds Lower Risk Without Del5qmentioning

confidence: 95%

“…A subgroup of patients with endogenous EPO levels ,100 U/L who had received previous ESA treatment, reached transfusion independence in 42.5% of the cases. 49 These 2 simple variables, ie, previous therapies and low endogenous EPO, could be used to select patients more prone to take advantage of lenalidomide after ESA failure, whereas investigation on molecular characteristics to better identify responsive subjects are ongoing. At present, no somatic mutation predicts for response.…”

Section: Mds Lower Risk Without Del5qmentioning

confidence: 99%

“…At present, no somatic mutation predicts for response. 49 Quite interestingly, the combination of lenalidomide and ESAs has also been recently shown to have additive effects in restoring erythropoiesis when ESAs fail, 50 and the results from 2 other just completed trials are awaited (www.clinicaltrials.gov: #NCT00843882; and EudraCT: #2008-002195-10). Consistent with results obtained with the single drug lenalidomide, patients with EPO levels ,100 U/L experienced higher erythroid responses; CRBNrs1672753 polymorphism was also predictive of erythroid improvement.…”

Section: Mds Lower Risk Without Del5qmentioning

confidence: 99%

“…[48][49][50][51][52] In the end, the majority of patients with lower-risk MDS would require RBC transfusions. 17 Given their relatively long survival, this support therapy is chronic and as such may create long-term side effects, as well as a social and economic burden.…”

Section: Mds Lower Risk Without Del5qmentioning

confidence: 99%

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Treatment of low-risk myelodysplastic syndromes

Santini

2016

Hematology

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The majority of myelodysplastic syndrome (MDS) patients belong to the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R) lower-risk categories. Their precise diagnostics and prognostic stratification is often a challenge, but may ensure the optimization of therapy. The availability of diverse treatment options has significantly improved the quality of life and survival of this group of patients. Anemia is the most relevant cytopenia in terms of frequency and symptoms in lower-risk MDS, and may be treated successfully with erythropoietic stimulating agents, provided a careful selection is performed on the basis of IPSS-R, endogenous erythropoietin levels, and transfusion independence. Doses and duration of therapy of erythropoietic-stimulating agents (ESAs) are critical to determine efficacy. In case a patient fails ESA treatment, the available options may include lenalidomide (approved for del5q positive cases), hypomethylating agents, and a rather large number of experimental agents, whose clinical trials should be offered to a larger number of MDS patients. The choice for second-line treatment must take into account biologic, cytogenetic, and molecular-identified characteristics of individual patients, as well as frailty and comorbidities. Other cytopenias are less frequently presenting as isolated. Specific therapy for thrombocytopenia has been proposed in experimental clinical trials with thrombomimetic agents that have shown good efficacy, but raised some safety concern. Although neutropenia is targeted symptomatically with growth factor supportive care, the immunosuppressive treatments are indicated mainly for pancytopenic, hypoplastic lower-risk MDS; they are not widely used because of their toxicity, despite the fact that they may induce responses. Finally, hematopoietic stem cell transplant is the curative option also for lower-risk MDS and timing should be carefully evaluated, balancing toxicity and the possibility of survival advantage. Finally, even when considered suitable for lower-risk MDS, transplant application is limited to the rarer fit and younger MDS patient.

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Patient Experience Captured by Quality-of-Life Measurement in Oncology Clinical Trials

et al. 2020

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IMPORTANCE Quality of life (QoL) is an important consideration in cancer medicine, especially because drugs are becoming more costly and may only result in modest gains in overall survival.However, there has been no descriptive analysis for the points at which QoL is measured in cancer trials.OBJECTIVE To estimate the prevalence of studies that measure QoL at different points and see how many studies measure QoL for the entirety of a patient's life. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional analysis includes all articles ononcology clinical trials in the 3 highest-impact oncology journals, published between July 2015 and June 2018, that reported QoL outcomes. MAIN OUTCOMES AND MEASURESData were abstracted on when QoL was assessed and the characteristics of these studies. RESULTSFor all 149 studies that met inclusion criteria, QoL assessment was high during treatment (104 articles [69.8%]), during follow-up (81 articles [54.4%]), and after the end of the intervention (68 articles [45.6%]). In 5 of the 149 studies (3.4%), QoL was assessed until death, including in only 1 of the 74 studies on metastatic or incurable cancers. Among these 5 studies, only 1 (20%) used a drug intervention, 1 (20%) used a behavioral intervention, and 2 (40%) used a radiation intervention; only 1 of 5 was in the metastatic setting. The number of studies that reported a positive QoL outcome (ie, QoL outcome was more favorable in the intervention group than in the control group) was between 42 of 81 articles (51.9%) and 16 of 28 articles (57.1%) for most QoL assessment points but only 1 of 5 articles (20%) for studies measuring QoL until death. CONCLUSIONS AND RELEVANCEThis study found that most clinical trials assessed QoL during the treatment or intervention and often during a given amount of follow-up but infrequently assessed QoL on disease progression and rarely followed QoL until the end of the patient's life. Most studies reporting QoL until the end of life reported worse QoL outcomes for the intervention group than the control group. Future research and policy recommendations should consider not just short-term QoL outcomes but QoL outcomes throughout the patient's cancer care. Question How often do oncology studies assess quality of life (QoL) throughout a patient's disease course? Findings This cross-sectional analysis of 149 oncology studies published in highimpact medical and oncology journals found that most studies (69.8%) assessed QoL during the intervention, whereas only 3.4% of studies assessed QoL until the time of death. Meaning These findings suggest that many oncology studies only assess QoL during the intervention; future research should consider the long-term outcomes throughout the patient's life.Oncology, and JAMA Oncology. For each of the journals, we searched for the term quality of life on the journal's website, and we limited the search to research articles only. Selected articles needed to (1) be an RCT, (2) have performed the analysis in the originally randomized groups, (3) have evaluated QoL in ...

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Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents

Cited by 192 publications

References 30 publications

Molecular predictors of response in patients with myeloid neoplasms treated with lenalidomide

Molecular predictors of response in patients with myeloid neoplasms treated with lenalidomide

Treatment of low-risk myelodysplastic syndromes

Patient Experience Captured by Quality-of-Life Measurement in Oncology Clinical Trials

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