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

Anita W Rijneveld*, Bronno van der Holt, Okke de Weerdt, Bart J Biemond, Arjan 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 van Sluis, Marie-Cecile J C Legdeur, Dries H Deeren, Alain Pa Gadisseur, Harm A M Sinnige, Dimitri BreemsAurélie Jaspers, Ollivier Legrand, Wim E Terpstra, Rinske Boersma, Dominiek Mazure, Agnes Triffet, Lidwine Tick, Karolien Anne Beel, Johan A Maertens, H Berna Beverloo, Marleen H Bakkus, Christa Homburg, Valerie de Haas, Vincent H J van der Velden, Jan J Cornelissen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Clofarabine (CLO) is a nucleoside analogue with efficacy in relapsed/refractory acute lymphoblastic leukemia (ALL). This randomized phase III study aimed to evaluate whether CLO added to induction and consolidation would improve outcome in adults with newly diagnosed ALL. Treatment for younger (18-40 years) patients consisted of a pediatric inspired protocol and for older patients (41-70 years) of a semi-intensive protocol was used. 340 patients were randomized. After a median follow up of 70 months, 5-year 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, while in patients >40 years EFS was 43% in both arms. 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 negative after consolidation 1 in arm A vs 75/81 (93%) in arm B (p=0.001). Seventy (42%) patients proceeded to allogeneic hematopoietic stem cell transplantation in both arms. Five years OS was similar in both arms, 60% vs 61%. Among patients achieving CR, relapse rates were 28% and 24%, and non-relapse 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. The trial is registered at www.trialregister.nl as NTR2004.

Original languageEnglish
Pages (from-to)1115–1125
Number of pages11
JournalBlood advances
Volume6
Issue number4
Early online date9 Dec 2021
DOIs
Publication statusPublished - 22 Feb 2022

Keywords

  • ACUTE LYMPHOBLASTIC-LEUKEMIA
  • MINIMAL RESIDUAL DISEASE
  • STEM-CELL TRANSPLANTATION
  • PEDIATRIC-PATIENTS
  • CLINICAL-SIGNIFICANCE
  • ONCOLOGY-GROUP
  • STANDARD-RISK
  • PHASE-II
  • CYCLOPHOSPHAMIDE
  • CHEMOTHERAPY

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