Blinatumomab added to prephase and consolidation therapy for adult B-ALL patients

During EHA 2024, Dr Anita Rijneveld, haematologist at the Erasmus Medical Center Cancer Institute in Rotterdam, presented the final results of the phase II HOVON-146 study. This study evaluated the addition of blinatumomab to the prephase and consolidation treatment of adult patients with B-cell acute lymphoblastic leukemia (B-ALL).

Despite a continuous optimization of chemotherapy regimens, the long-term prognosis for adult patients with B-ALL remains to be poor. To improve on this, several studies are evaluating the integration of novel therapeutic agents in the first line treatment of adult B-ALL patients.

In HOVON-146, 71 adult B-ALL patients were treated with a paediatric-inspired prephase and consolidation treatment protocol. After 2 cycles of blinatumomab in the prephase, already 63% of patients had a complete response (CR), with an MRD-negativity rate of 53%. Importantly, this high rate of CR after the prephase was obtained without the use of any chemotherapy. After the consolidation phase, during which patients received an additional 4 weeks of blinatumomab in conjunction with consolidation chemotherapy, the CR rate had increased to 97%, with MRD-negativity in 91% of patients.

The 4-year overall survival (OS) rate obtained with the blinatumomab-containing regimen in this study was reported at 86% in the cohorts of patients ≤40 years of age and in patients aged 40-60 years. In patients above the age of 60, the OS rate at 4 years was somewhat lower at 50%. In the subgroup of patients with Philadelphia chromosome positive (Ph+) ALL, the 4-year OS rate reached 85%. The survival rates obtained in HOVON-146 compare favourably to the results obtained in HOVON-100, a clinical trial evaluating a similar chemotherapy regimen without blinatumomab (4-year OS in patients ≤40 years: 76% [vs. 86%], >40 years: 51% [vs. 71%]).

For Dr Rijneveld, these data underscore the potential of blinatumomab in the first line treatment of adult B-ALL, especially for elderly patients and for those with Ph+ disease. To evaluate this in more detail, dedicated phase III randomized controlled trials are warranted in which blinatumomab is added to first line chemotherapy, or in which (parts of) the chemotherapy backbone are substituted for blinatumomab.