Carfilzomib plus induction chemotherapy for children with relapsed or refractory acute lymphoblastic leukemia

Abstract We report outcomes of the phase 2 study combining carfilzomib (CFZ) and VXLD (vincristine, dexamethasone, asparaginase, and daunorubicin; CFZ-VXLD) in heavily pretreated, pediatric patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). We investigated whether postinduction complete remission (CR) rates after CFZ-VXLD induction are superior to an external real-world control (EC). Patients aged ≥1 month to <21 years with R/R ALL received CFZ-VXLD induction, followed by optional consolidation (experimental arm). The EC arm included similar patients receiving real-world, curative-intent regimens at Therapeutic Advances in Childhood Leukemia sites between 2000 and 2023. The primary end point was CR after induction; overall response rate (ORR; CR/CR with partial/incomplete hematologic recovery/CR without platelet recovery) was a secondary end point. Comparative analyses used inverse probability of treatment weighting. Experimental and EC arms included 105 and 140 patients, respectively. CR rates after induction were 14.8% vs 7.8% (odds ratio [OR], 2.04; 95% confidence interval [CI], 0.54-7.66) in patients with B-cell ALL (B-ALL) and 13.6% vs 9.1% (OR, 1.58; 95% CI, 0.47-5.31) in patients with T-cell ALL. There was no statistically significant increase in postinduction CR for the CFZ-VXLD arm vs the EC arm and the study did not meet its primary end point. In patients with B-ALL, ORR was 42.6% vs 26.3%, favoring the CFZ-VXLD arm vs the EC arm. Adverse event rates with CFZ were consistent with previous reports. Overall, the CFZ-VXLD regimen may be an option for some selected pediatric patients with R/R ALL, and this study highlights that novel treatments for R/R ALL remain an area of unmet medical need. This trial was registered at www.clinicaltrials.gov as NCT02303821.