The combination of bortezomib with chemotherapy to treat relapsed/refractory acute lymphoblastic leukaemia of childhood

The combination of bortezomib with chemotherapy to treat relapsed/refractory acute lymphoblastic leukaemia of childhood
Previous Phase I and II studies have shown that bortezomib, a proteasome inhibitor, has acceptable toxicities and a therapeutic effect in patients with relapsed ALL. This study describes the results of a single centre study which looked at the rate of CR in patients with relapsed/refractory ALL who received a combination of bortezomib and standard salvage chemotherapies.
37 pediatric patients (30 with relapsed/refractory B ALL and 7 with relapsed/refractory T ALL), were enrolled in the study. Bortezomib was administered four times in the first month of treatment, in combination with a standard salvage therapy, including dexamethasone, doxorubicin, vincristine, PEG-asparaginase and IT methotrexate. Response to treatment was assessed morphology, cytogenetics and immunophenotyping on day 29.
Twenty-two of 30 B-ALL patients (73%) and five of seven T-ALL patients (71%) achieved CR with the addition of bortezomib to their chemotherapy regimen. Fourteen of the 37 patients had a negative MRD at the end of therapy resulting in a higher 2-year OS of 68.4%. The MRD positive group had dismal survival.
The main limitations of this study include the small sample size, involvement of a single centre and lack of head to head comparison via a randomized control trial.
Bortezomib has been shown to be safe in combination with standard salvage chemotherapy. Where cytotoxic agents such as bortezomib fit in the treatment of relapsed/refractory ALL in the age of immunotherapy is not clear.