Benefits and risks of clofarabine in adult acute lymphoblastic leukemia investigated in depth by multi-state modeling.
Cancer Med
; 13(9): e6756, 2024 May.
Article
de En
| MEDLINE
| ID: mdl-38680089
ABSTRACT
BACKGROUND:
We recently reported results of the prospective, open-label HOVON-100 trial in 334 adult patients with acute lymphoblastic leukemia (ALL) randomized to first-line treatment with or without clofarabine (CLO). No improvement of event-free survival (EFS) was observed, while a higher proportion of patients receiving CLO obtained minimal residual disease (MRD) negativity.AIM:
In order to investigate the effects of CLO in more depth, two multi-state models were developed to identify why CLO did not show a long-term survival benefit despite more MRD-negativity.METHODS:
The first model evaluated the effect of CLO on going off-protocol (not due to refractory disease/relapse, completion or death) as a proxy of severe treatment-related toxicity, while the second model evaluated the effect of CLO on obtaining MRD negativity. The subsequent impact of these intermediate events on death or relapsed/refractory disease was assessed in both models.RESULTS:
Overall, patients receiving CLO went off-protocol more frequently than control patients (35/168 [21%] vs. 18/166 [11%], p = 0.019; HR 2.00 [1.13-3.52], p = 0.02), especially during maintenance (13/44 [30%] vs. 6/56 [11%]; HR 2.85 [95%CI 1.08-7.50], p = 0.035). Going off-protocol was, however, not associated with more relapse or death. Patients in the CLO arm showed a trend towards an increased rate of MRD-negativity compared with control patients (HR MRD-negativity 1.35 [0.95-1.91], p = 0.10), which did not translate into a significant survival benefit.CONCLUSION:
We conclude that the intermediate states, i.e., going off-protocol and MRD-negativity, were affected by adding CLO, but these transitions were not associated with subsequent survival estimates, suggesting relatively modest antileukemic activity in ALL.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladie résiduelle
/
Leucémie-lymphome lymphoblastique à précurseurs B et T
/
Clofarabine
Limites:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Cancer Med
Année:
2024
Type de document:
Article
Pays d'affiliation:
Pays-Bas
Pays de publication:
États-Unis d'Amérique