Dataset Information

Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin.

ABSTRACT:

Purpose

Impaired response to erythropoietin underlies ineffective erythropoiesis and anemia in myelodysplastic syndromes (MDS). We investigated whether treatment with lenalidomide (LEN), which augments erythropoietin receptor signaling in vitro, can restore and improve hemoglobin response to epoetin (EPO) alfa in patients with lower-risk, non-del(5q) MDS who have anemia that is refractory to or have low probability of benefit from treatment with recombinant erythropoietin.

Methods

In a phase III, US intergroup trial, we randomly assigned patients to receive either LEN and EPO alfa or LEN alone following stratification by serum erythropoietin concentration and prior erythropoietin treatment.

Results

A total of 195 evaluable patients were randomly assigned: 99 patients to the LEN-EPO alfa cohort and 96 to LEN alone. After four cycles of treatment, the primary end point of major erythroid response (MER) was significantly higher (28.3%) with the combination compared with LEN alone (11.5%) (P = .004). Among 136 patients who completed 16 weeks of study treatment, 38.9% and 15.6% achieved MER, respectively (P = .004). Additionally, minor erythroid response was achieved in 18.2% and 20.8% of patients, for an overall erythroid response rate of 46.5% versus 32.3%. Among LEN nonresponders, 38 crossed over to the addition of EPO alfa with 10 patients (26.3%) achieving a MER. Responses to the combined treatment were highly durable with a median MER duration of 23.8 months compared with 13 months with LEN alone.

Conclusion

LEN restores sensitivity to recombinant erythropoietin in growth factor-insensitive, lower-risk, non-del(5q) MDS, to yield a significantly higher rate and duration of MER compared with LEN alone (funded by the National Cancer Institute; E2905 ClinicalTrials.gov identifier: NCT02048813).

SUBMITTER: List AF

PROVIDER: S-EPMC8274743 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin.

List Alan F AF Sun Zhuoxin Z Verma Amit A Bennett John M JM Komrokji Rami S RS McGraw Kathy K Maciejewski Jaroslaw J Altman Jessica K JK Cheema Puneet S PS Claxton David F DF Luger Selina M SM Mattison Ryan J RJ Wassenaar Timothy R TR Artz Andrew S AS Schiffer Charles A CA Litzow Mark R MR Tallman Martin S MS

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20210113 9

<h4>Purpose</h4>Impaired response to erythropoietin underlies ineffective erythropoiesis and anemia in myelodysplastic syndromes (MDS). We investigated whether treatment with lenalidomide (LEN), which augments erythropoietin receptor signaling in vitro, can restore and improve hemoglobin response to epoetin (EPO) alfa in patients with lower-risk, non-del(5q) MDS who have anemia that is refractory to or have low probability of benefit from treatment with recombinant erythropoietin.<h4>Methods</h4 ...[more]

PMID: 33439748

Similar Datasets

Project description:Background and objectivesThis study was conducted to compare the safety and efficacy of intravenous epoetin alfa-epbx, an epoetin alfa biosimilar, to epoetin alfa in patients on hemodialysis with ESKD and anemia.Design, setting, participants, & measurementsIn this 24-week, multicenter, double-blind comparative efficacy and safety study, 612 patients on hemodialysis with ESKD and anemia who had stable hemoglobin and were receiving stable doses of intravenous epoetin alfa were randomized (1:1) to intravenous epoetin alfa or epoetin alfa-epbx. Dosing was adjusted according to the epoetin alfa prescribing information. The coprimary efficacy end points were the least squares mean difference between the two treatments in mean weekly hemoglobin level and mean weekly epoetin dose per kilogram of body weight during the last 4 weeks of treatment.ResultsThe least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly hemoglobin was -0.12 g/dl and the 95% confidence interval (-0.25 to 0.01) was contained within the prespecified equivalence margin (-0.5 to 0.5 g/dl). The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly epoetin dose per kilogram of body weight was 0.37 U/kg per week, and the 95% confidence interval (-10.40 to 11.13) was contained within the prespecified equivalence margin (-45 to 45 U/kg per week). Incidences of adverse events (77.1% versus 75.3%), serious adverse events (24.9% versus 27.0%), and deaths (n=5 versus 6) were similar between the epoetin alfa-epbx and epoetin alfa groups, respectively. Five patients tested positive for anti-recombinant human erythropoietin antibodies at baseline, and two additional patients (n=1 per group) developed anti-recombinant human erythropoietin antibodies while on study treatment. All patients tested negative for neutralizing antibodies, and no patient in either group experienced an event of pure red cell aplasia.ConclusionsThis 24-week, comparative, clinical trial in patients on hemodialysis with ESKD and anemia demonstrated there is no clinically meaningful difference in efficacy or safety between epoetin alfa-epbx and epoetin alfa.

Project description:BackgroundAdequately powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking.Study designObservational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis therapy in facilities (almost) exclusively using DPO versus EPO.Setting & participantsNonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure.InterventionDPO versus EPO.OutcomesAll-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke.MeasurementsUnadjusted and adjusted HRs from Cox proportional hazards regression models.ResultsOf 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9,465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99-1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94-1.16). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. We found no differences in adjusted stroke or MI rates or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96-1.25).LimitationsNonrandom treatment assignment, potential residual confounding.ConclusionsIn incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.

Dataset Information

Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin.

Purpose

Methods

Results

Conclusion

Publications

Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets