KEY TAKEAWAYS
- The study aimed to investigate the impact of CLO on EFS and MRD negativity in patients with ALL
- Researchers found that CLO affected intermediate states, such as going off-protocol and MRD-negativity, but didn’t impact subsequent survival estimates in adult ALL.
Sjoerd J F Hermans and the team reported the results of the prospective, open-label HOVON-100 trial, involving 334 adult patients diagnosed with acute lymphoblastic leukemia (ALL). In this trial, patients were randomized to receive first-line (1L) treatment with or without clofarabine (CLO).
Despite adding clofarabine, no improvement in event-free survival (EFS) was observed. However, a notable finding was a higher proportion of patients who received CLO achieved minimal residual disease (MRD) negativity.
They performed an inclusive analysis to evaluate clofarabine’s effects on intermediate events in the HOVON-100 trial. The first model assessed CLO’s impact on patients going off-protocol, excluding cases due to refractory disease, completion, or death, as a measure of severe treatment-related toxicity. The second model examined CLO’s influence on achieving MRD negativity. Subsequently, the impact of these intermediate events on death or relapsed/refractory disease was assessed in both models.
The 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.
The study concluded that the addition of CLO affected intermediate states, such as going off-protocol and MRD-negativity, yet these transitions did not correlate with subsequent survival estimates. This suggests relatively modest antileukemic activity in adult ALL.
No funding information was provided.
Source: https://pubmed.ncbi.nlm.nih.gov/38680089/
Hermans SJF, van Norden Y, Versluis J, et al. (2024). “Benefits and risks of clofarabine in adult acute lymphoblastic leukemia investigated in depth by multi-state modeling.” Cancer Med. 2024 May;13(9):e6756. doi: 10.1002/cam4.6756. PMID: 38680089; PMCID: PMC11056700.
