InO, an anti-CD22 antibody-calicheamicin conjugate, has shown activity in relapsed and refractory acute lymphoblastic leukemia (ALL) in an ongoing phase 3 trial (INO-VATE). This assessment demonstrates that InO is highly effective in older patients with relapsed/refractory ALL for whom treatment options are currently limited. Remission rates and duration of response are similar when comparing age groups, whereas minimal residual disease–negativity rates among responders are numerically higher in older patients. Safety of InO is generally similar for older patients versus younger patients.
Ponatinib is a multitargeted tyrosine kinase inhibitor (TKI) that potently inhibits BCR-ABL1 compared with previous generations of TKIs. Results of this large meta-analysis show that ponatinib combined with chemotherapy is associated with superior efficacy in newly diagnosed Philadelphia-positive ALL compared with combinations that include first- and second-generation TKIs. Specifically, ponatinib demonstrated a significant 9-fold increase in the odds of complete morphologic response.
In this study, data were collected for 1509 adults and children with Philadelphia-negative ALL who were treated according to the NOPHO ALL2008 protocol. Patients were registered in a database upon diagnosis and subsequently followed systematically every 3 months. Event-free survival for adult patients with ALL improved markedly after NOPHO ALL2008 treatment compared with historical data. Although adult patients are more likely to have higher-risk ALL, their overall cure rates approach those of children with ALL when stratified by risk group.
Achievement of complete response (CR) in relapsed and refractory pediatric ALL is relatively rare, especially after multiple relapses. Bortezomib, a proteasome inhibitor approved for use in multiple myeloma and relapsed non-Hodgkin lymphoma, has activity against ALL blasts. This study evaluated bortezomib combined with vincristine, dexamethasone, pegylated asparaginase, and doxorubicin as a salvage treatment in 24 children with B-cell precursor and 7 children with T-cell ALL. Twenty of these 31 patients achieved CR, including 10 with minimal residual disease <0.1%, leading to a 65% overall response rate. Intensive antibacterial and antifungal prophylaxis are recommended.
