Valeria Santini1, Antonio Almeida2, Aristoteles Giagounidis2, Stefanie Gröpper2, Anna Jonasova2, Norbert Vey2, Ghulam J Mufti2, Rena Buckstein2, Moshe Mittelman2, Uwe Platzbecker2, Ofer Shpilberg2, Ron Ram2, Consuelo Del Cañizo2, Norbert Gattermann2, Keiya Ozawa2, Alberto Risueño2, Kyle J MacBeth2, Jianhua Zhong2, Francis Séguy2, Albert Hoenekopp2, C L Beach2, Pierre Fenaux2. 1. Valeria Santini, University of Florence, Florence, Italy; Antonio Almeida, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal; Aristoteles Giagounidis and Stefanie Gröpper, Marien Hospital Düsseldorf; Norbert Gattermann, Heinrich-Heine-Universität, Düsseldorf; Uwe Platzbecker, Technical University Dresden, Dresden, Germany; Anna Jonasova, Charles University General Hospital, Prague, Czech Republic; Norbert Vey, Centre Régional de Lutte Contre le Cancer, Marseille; Pierre Fenaux, Université Paris, Paris, France; Francis Séguy and Albert Hoenekopp, Celgene International, Boudry, Switzerland; Ghulam J. Mufti, King's College Hospital, London, United Kingdom; Rena Buckstein, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Moshe Mittelman and Ron Ram, Tel Aviv University; Ofer Shpilberg, Assuta Medical Center, Tel Aviv, Israel; Consuelo del Cañizo, Hospital Universitario de Salamanca, Salamanca; Alberto Risueño, Celgene Institute for Translational Research Europe, Seville, Spain; Keiya Ozawa, The University of Tokyo, Tokyo, Japan; Kyle J. MacBeth, Celgene Corporation, San Francisco, CA; and Jianhua Zhong and C.L. Beach, Celgene Corporation, Summit, NJ. valeria.santini@unifi.it. 2. Valeria Santini, University of Florence, Florence, Italy; Antonio Almeida, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal; Aristoteles Giagounidis and Stefanie Gröpper, Marien Hospital Düsseldorf; Norbert Gattermann, Heinrich-Heine-Universität, Düsseldorf; Uwe Platzbecker, Technical University Dresden, Dresden, Germany; Anna Jonasova, Charles University General Hospital, Prague, Czech Republic; Norbert Vey, Centre Régional de Lutte Contre le Cancer, Marseille; Pierre Fenaux, Université Paris, Paris, France; Francis Séguy and Albert Hoenekopp, Celgene International, Boudry, Switzerland; Ghulam J. Mufti, King's College Hospital, London, United Kingdom; Rena Buckstein, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Moshe Mittelman and Ron Ram, Tel Aviv University; Ofer Shpilberg, Assuta Medical Center, Tel Aviv, Israel; Consuelo del Cañizo, Hospital Universitario de Salamanca, Salamanca; Alberto Risueño, Celgene Institute for Translational Research Europe, Seville, Spain; Keiya Ozawa, The University of Tokyo, Tokyo, Japan; Kyle J. MacBeth, Celgene Corporation, San Francisco, CA; and Jianhua Zhong and C.L. Beach, Celgene Corporation, Summit, NJ.
Abstract
PURPOSE: This international phase III, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of lenalidomide in RBC transfusion-dependent patients with International Prognostic Scoring System lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. PATIENTS AND METHODS: In total, 239 patients were randomly assigned (2:1) to treatment with lenalidomide (n = 160) or placebo (n = 79) once per day (on 28-day cycles). The primary end point was the rate of RBC transfusion independence (TI) ≥ 8 weeks. Secondary end points were RBC-TI ≥ 24 weeks, duration of RBC-TI, erythroid response, health-related quality of life (HRQoL), and safety. RESULTS:RBC-TI ≥ 8 weeks was achieved in 26.9% and 2.5% of patients in the lenalidomide and placebo groups, respectively (P < .001). Ninety percent of patients achieving RBC-TI responded within 16 weeks of treatment. Median duration of RBC-TI with lenalidomide was 30.9 weeks (95% CI, 20.7 to 59.1). Transfusion reduction of ≥ 4 units packed RBCs, on the basis of a 112-day assessment, was 21.8% in the lenalidomide group and 0% in the placebo group. Higher response rates were observed in patients with lower baseline endogenous erythropoietin ≤ 500 mU/mL (34.0% v 15.5% for > 500 mU/mL). At week 12, mean changes in HRQoL scores from baseline did not differ significantly between treatment groups, which suggests that lenalidomide did not adversely affect HRQoL. Achievement of RBC-TI ≥ 8 weeks was associated with significant improvements in HRQoL (P < .01). The most common treatment-emergent adverse events were neutropenia and thrombocytopenia. CONCLUSION:Lenalidomide yields sustained RBC-TI in 26.9% of RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Response to lenalidomide was associated with improved HRQoL. Treatment-emergent adverse event data were consistent with the known safety profile of lenalidomide.
RCT Entities:
PURPOSE: This international phase III, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of lenalidomide in RBC transfusion-dependent patients with International Prognostic Scoring System lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. PATIENTS AND METHODS: In total, 239 patients were randomly assigned (2:1) to treatment with lenalidomide (n = 160) or placebo (n = 79) once per day (on 28-day cycles). The primary end point was the rate of RBC transfusion independence (TI) ≥ 8 weeks. Secondary end points were RBC-TI ≥ 24 weeks, duration of RBC-TI, erythroid response, health-related quality of life (HRQoL), and safety. RESULTS: RBC-TI ≥ 8 weeks was achieved in 26.9% and 2.5% of patients in the lenalidomide and placebo groups, respectively (P < .001). Ninety percent of patients achieving RBC-TI responded within 16 weeks of treatment. Median duration of RBC-TI with lenalidomide was 30.9 weeks (95% CI, 20.7 to 59.1). Transfusion reduction of ≥ 4 units packed RBCs, on the basis of a 112-day assessment, was 21.8% in the lenalidomide group and 0% in the placebo group. Higher response rates were observed in patients with lower baseline endogenous erythropoietin ≤ 500 mU/mL (34.0% v 15.5% for > 500 mU/mL). At week 12, mean changes in HRQoL scores from baseline did not differ significantly between treatment groups, which suggests that lenalidomide did not adversely affect HRQoL. Achievement of RBC-TI ≥ 8 weeks was associated with significant improvements in HRQoL (P < .01). The most common treatment-emergent adverse events were neutropenia and thrombocytopenia. CONCLUSION:Lenalidomide yields sustained RBC-TI in 26.9% of RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Response to lenalidomide was associated with improved HRQoL. Treatment-emergent adverse event data were consistent with the known safety profile of lenalidomide.
Authors: U Platzbecker; P Fenaux; L Adès; A Giagounidis; V Santini; A A van de Loosdrecht; D Bowen; T de Witte; G Garcia-Manero; E Hellström-Lindberg; U Germing; R Stauder; L Malcovati; Mikkael A Sekeres; David P Steensma; S Gloaguen Journal: Blood Date: 2018-11-07 Impact factor: 22.113
Authors: G Kerdivel; V Chesnais; E Becht; A Toma; N Cagnard; F Dumont; A Rousseau; P Fenaux; S Chevret; N Chapuis; V Boeva; W H Fridman; M Fontenay; O Kosmider Journal: Leukemia Date: 2017-10-03 Impact factor: 11.528
Authors: Maximilian Stahl; Michelle DeVeaux; Theo de Witte; Judith Neukirchen; Mikkael A Sekeres; Andrew M Brunner; Gail J Roboz; David P Steensma; Vijaya R Bhatt; Uwe Platzbecker; Thomas Cluzeau; Pedro H Prata; Raphaël Itzykson; Pierre Fenaux; Amir T Fathi; Alexandra Smith; Ulrich Germing; Ellen K Ritchie; Vivek Verma; Aziz Nazha; Jaroslaw P Maciejewski; Nikolai A Podoltsev; Thomas Prebet; Valeria Santini; Steven D Gore; Rami S Komrokji; Amer M Zeidan Journal: Blood Adv Date: 2018-07-24
Authors: Rami Komrokji; Arlene S Swern; David Grinblatt; Roger M Lyons; Magnus Tobiasson; Lewis R Silverman; Hamid Sayar; Ravi Vij; Albert Fliss; Nora Tu; Mary M Sugrue Journal: Oncologist Date: 2017-11-08