TY - JOUR
T1 - Clofarabine added to intensive treatment in adult patients with newly diagnosed ALL
T2 - the HOVON-100 trial
AU - Rijneveld, Anita W.
AU - van der Holt, Bronno
AU - the Dutch-Belgian HOVON Cooperative group
AU - de Weerdt, Okke
AU - Biemond, Bart J.
AU - van de Loosdrecht, Arjen A.
AU - van der Wagen, Lotte E.
AU - Bellido, Mar
AU - van Gelder, Michel
AU - van der Velden, Walter J.F.M.
AU - Selleslag, Dominik
AU - van Lammeren-Venema, Danie€lle
AU - Halkes, Constantijn J.M.
AU - Fijnheer, Rob
AU - Havelange, Violaine
AU - van Sluis, Geerte L.
AU - Legdeur, Marie Cecile
AU - Deeren, Dries
AU - Gadisseur, Alain
AU - Sinnige, Harm A.M.
AU - Breems, Dimitri A.
AU - Jaspers, Aurelie
AU - Legrand, Ollivier
AU - Terpstra, Wim E.
AU - Boersma, Rinske S.
AU - Mazure, Dominiek
AU - Triffet, Agnes
AU - Tick, Lidwine W.
AU - Beel, Karolien
AU - Maertens, Johan A.
AU - Beverloo, H. Berna
AU - Bakkus, Marleen
AU - Homburg, Christa H.E.
AU - de Haas, Valerie
AU - van der Velden, Vincent H.J.
AU - Cornelissen, Jan J.
N1 - Funding Information: The authors would like to thank all laboratory technicians at Erasmus MC in Rotterdam, Sanquin in Amsterdam, VUB in Brussels, and SKION in Utrecht, all in the Netherlands. They would also like to thank the local institutional data managers as well as the HOVON Data Center Trial team for their support. The authors would also like to thank the members of the Data Safety and Monitoring Board: R. Pieters (Utrecht, The Netherlands), N. Gokbuget € (Frankfurt, Germany), and V. Levy (Paris, France). The authors thank The Dutch Cancer Foundation for financial support (grant 2008-4330). This investigator-sponsored trial was financially supported by Sanofi-Genzyme, and the drug clofarabine was provided free of charge.
Publisher Copyright: © 2022 by The American Society of Hematology.
PY - 2022/2/22
Y1 - 2022/2/22
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85125346233
U2 - 10.1182/bloodadvances.2021005624
DO - 10.1182/bloodadvances.2021005624
M3 - Article
C2 - 34883506
AN - SCOPUS:85125346233
SN - 2473-9529
VL - 6
SP - 1115
EP - 1125
JO - Blood advances
JF - Blood advances
IS - 4
ER -