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

Rijneveld, A.W.; Holt, B. van der; Weerdt, O. de; Biemond, B.J.; Loosdrecht, A.A. van de; Wagen, L.E. van der; ... ; Dutch-Belgian HOVON Cooperative Gr (2022)

Article / Letter to editor

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.

• All authors: Rijneveld, A.W.; Holt, B. van der; Weerdt, O. de; Biemond, B.J.; Loosdrecht, A.A. van de; Wagen, L.E. van der; Bellido, M.; Gelder, M. van; Velden, W.J.F.M. van der; Selleslag, D.; Lammeren-Venema, D. van; Halkes, C.J.M.; Fijnheer, R.; Havelange, V.; Sluis, G.L. van; 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.; Haas, V. de; Velden, V.H.J. van der; Cornelissen, J.J.; Dutch-Belgian HOVON Cooperative Gr
• Date: 2022-02-12
• Journal: Blood Advances
• Volume: 6
• Issue: 4
• Pages: 1115 - 1125
• DOI: doi:10.1182/bloodadvances.2021005624