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Clofarabine added to intensive treatment in adult patients with newly diagnosed ALL:the HOVON-100 trial

Authors :
Rijneveld, Anita W.
van der Holt, Bronno
de Weerdt, Okke
Biemond, Bart J.
van de Loosdrecht, Arjen A.
van der Wagen, Lotte E.
Bellido, Mar
van Gelder, Michel
van der Velden, Walter J.F.M.
Selleslag, Dominik
van Lammeren-Venema, Danie€lle
Halkes, Constantijn J.M.
Fijnheer, Rob
Havelange, Violaine
van Sluis, Geerte L.
Legdeur, Marie Cecile
Deeren, Dries
Gadisseur, Alain
Sinnige, Harm A.M.
Breems, Dimitri A.
Jaspers, Aurelie
Legrand, Ollivier
Terpstra, Wim E.
Boersma, Rinske S.
Mazure, Dominiek
Triffet, Agnes
Tick, Lidwine W.
Beel, Karolien
Maertens, Johan A.
Beverloo, H. Berna
Bakkus, Marleen
Homburg, Christa H.E.
de Haas, Valerie
van der Velden, Vincent H.J.
Cornelissen, Jan J.
Rijneveld, Anita W.
van der Holt, Bronno
de Weerdt, Okke
Biemond, Bart J.
van de Loosdrecht, Arjen A.
van der Wagen, Lotte E.
Bellido, Mar
van Gelder, Michel
van der Velden, Walter J.F.M.
Selleslag, Dominik
van Lammeren-Venema, Danie€lle
Halkes, Constantijn J.M.
Fijnheer, Rob
Havelange, Violaine
van Sluis, Geerte L.
Legdeur, Marie Cecile
Deeren, Dries
Gadisseur, Alain
Sinnige, Harm A.M.
Breems, Dimitri A.
Jaspers, Aurelie
Legrand, Ollivier
Terpstra, Wim E.
Boersma, Rinske S.
Mazure, Dominiek
Triffet, Agnes
Tick, Lidwine W.
Beel, Karolien
Maertens, Johan A.
Beverloo, H. Berna
Bakkus, Marleen
Homburg, Christa H.E.
de Haas, Valerie
van der Velden, Vincent H.J.
Cornelissen, Jan J.
Source :
Rijneveld , A W , van der Holt , B , the Dutch-Belgian HOVON Cooperative group , de Weerdt , O , Biemond , B J , van de Loosdrecht , A A , van der Wagen , L E , Bellido , M , van Gelder , M , van der Velden , W J F M , Selleslag , D , van Lammeren-Venema , D , Halkes , C J M , Fijnheer , R , Havelange , V , van Sluis , G L , Legdeur , M C , Deeren , D , Gadisseur , A , Sinnige , H A M , Breems , D A , Jaspers , A , Legrand , O , Terpstra , W E , Boersma , R S , Mazure , D , Triffet , A , Tick , L W , Beel , K , Maertens , J A , Beverloo , H B , Bakkus , M , Homburg , C H E , de Haas , V , van der Velden , V H J & Cornelissen , J J 2022 , ' Clofarabine added to intensive treatment in adult patients with newly diagnosed ALL : the HOVON-100 trial ' , Blood advances , vol. 6 , no. 4 , pp. 1115-1125 .
Publication Year :
2022

Abstract

Clofarabine (CLO) is a nucleoside analog with efficacy in relapsed/refractory acute lymphoblastic leukemia (ALL). This randomized phase 3 study aimed to evaluate whether CLO added to induction and whether consolidation would improve outcome in adults with newly diagnosed ALL. Treatment of younger (18-40 years) patients consisted of a pediatric-inspired protocol, and for older patients (41-70 years), a semi-intensive protocol was used. Three hundred and forty patients were randomized. After a median follow-up of 70 months, 5-year event-free survival (EFS) was 50% and 53% for arm A and B (CLO arm). For patients #40 years, EFS was 58% vs 65% in arm A vs B, whereas in patients .40 years, EFS was 43% in both arms. Complete remission (CR) rate was 89% in both arms and similar in younger and older patients. Minimal residual disease (MRD) was assessed in 200 patients (60%). Fifty-four of 76 evaluable patients (71%) were MRD2 after consolidation 1 in arm A vs 75/81 (93%) in arm B (P 5 .001). Seventy (42%) patients proceeded to allogeneic hematopoietic stem cell transplantation in both arms. Five-year overall survival (OS) was similar in both arms: 60% vs 61%. Among patients achieving CR, relapse rates were 28% and 24%, and nonrelapse mortality was 16% vs 17% after CR. CLO-treated patients experienced more serious adverse events, more infections, and more often went off protocol. This was most pronounced in older patients. We conclude that, despite a higher rate of MRD negativity, addition of CLO does not improve outcome in adults with ALL, which might be due to increased toxicity.

Details

Database :
OAIster
Journal :
Rijneveld , A W , van der Holt , B , the Dutch-Belgian HOVON Cooperative group , de Weerdt , O , Biemond , B J , van de Loosdrecht , A A , van der Wagen , L E , Bellido , M , van Gelder , M , van der Velden , W J F M , Selleslag , D , van Lammeren-Venema , D , Halkes , C J M , Fijnheer , R , Havelange , V , van Sluis , G L , Legdeur , M C , Deeren , D , Gadisseur , A , Sinnige , H A M , Breems , D A , Jaspers , A , Legrand , O , Terpstra , W E , Boersma , R S , Mazure , D , Triffet , A , Tick , L W , Beel , K , Maertens , J A , Beverloo , H B , Bakkus , M , Homburg , C H E , de Haas , V , van der Velden , V H J & Cornelissen , J J 2022 , ' Clofarabine added to intensive treatment in adult patients with newly diagnosed ALL : the HOVON-100 trial ' , Blood advances , vol. 6 , no. 4 , pp. 1115-1125 .
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1376785145
Document Type :
Electronic Resource