Bortezomib Combination Therapy of Relapsed and Refractory Acute Lymphoblastic Leukemia in Children

Abstract

Background & Aims. Despite significant success in the treatment of acute lymphoblastic leukemia (ALL) in children, relapses and drug resistance to the standard therapy remain the main cause of treatment failure. The addition of bortezomib to the combination therapy of relapsed ALL to change the sensitivity of blast cells may be a perspective approach to cure patients. The aim was to evaluate the efficacy and toxicity of the anti-relapse ALL treatment protocols REZ BFM 95/96 without bortezomib and COG AALL07P1 with bortezomib in relapsed and refractory ALL in children. Materials & Methods. The study included 54 children with a confirmed ALL of various localizations. From 1995 to 2011, ALL REZ BFM 95/96 treatment without bortezomib was administered to 26 patients. From 2011 to 2016, 28 children received COG AALL07P1 combination treatment with bortezomib. Results. The immediate treatment efficacy significantly higher in patients treated with bortezomib (85.7 % vs 57.6 %) after induction chemotherapy with the ALL REZ BFM 95/96. The analysis of the long-term outcomes (disease-free, event-free, overall survival) showed no significant differences between the groups. The event-free survival of patients with isolated bone marrow relapses for a period of 2 years was 20.3 ± 17.5 %. The tolerability of the program was acceptable, complications developing during myelosuppression were not associated with the administration of bortezomib. Conclusion. The intensification of induction chemotherapy according to COG AALL07P1 protocol with the addition of bortezomib allowed to increase the number of complete remissions including MRD negative ones.

Bortezomib advanced mechanisms of action in multiple myeloma, solid and liquid tumors along with its novel therapeutic applications

“…The endpoints of standard risk (SR) and intermediate risk (IR) patients with T-ALL and T-LL treated with BTZ were successfully achieved through an improved 3-year EFS and OS. Therapy intensification allowed elimination of cranial radiation (CXRT) in the majority of patients without excessive relapse (Batmanova et al, 2017[ 11 ]). Thus, proving the importance of BTZ in standard therapy for de novo T-LL appears advantageous.…”