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

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 MRD- after consolidation 1 in arm A vs 75/81 (93%) in arm B (P = .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. This trial was registered at www.trialregister.nl as #NTR2004.

• Authors: Anita W Rijneveld, Bronno van der Holt, Okke de Weerdt, Bart J Biemond, Arjen A van de Loosdrecht, Lotte E van der Wagen, Mar Bellido, Michel van Gelder, Walter J F M van der Velden, Dominik Selleslag, Daniëlle van Lammeren-Venema, Constantijn J M Halkes, Rob Fijnheer, Violaine Havelange, Geerte L van Sluis, Marie-Cecile Legdeur, Dries Deeren, Alain Gadisseur, Harm A M Sinnige, Dimitri A Breems, Aurélie Jaspers, Ollivier Legrand, Wim E Terpstra, Rinske S Boersma, Dominiek Mazure, Agnes Triffet, Lidwine W Tick, Karolien Beel, Johan A Maertens, H Berna Beverloo, Marleen Bakkus, Christa H E Homburg, Valerie de Haas, Vincent H J van der Velden, Jan J Cornelissen, Dutch-Belgian HOVON Cooperative group
• Journal: Blood advances (Blood Adv) Vol. 6 Issue 4 Pg. 1115-1125 (02 22 2022) ISSN: 2473-9537 [Electronic] United States
• PMID: 34883506 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• Clofarabine

Topics

• Adult
• Aged
• Child
• Clofarabine
• Hematopoietic Stem Cell Transplantation
• Humans
• Neoplasm, Residual
• Recurrence
• Remission Induction