The efficacy of bortezomib during induction therapy in patients with high-risk acute lymphoblastic leukemia

Camila Terreros-Palacios, Department of Hematology. Mexico
Daniela Pérez-Sámano, Department of Hematology. Mexico
Adán G. Gallardo-Rodríguez, Department of Hematology, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico
Irma Olarte-Carrillo, Molecular Biology Laboratory, Department of Hematology, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico
Carlos Martínez-Murillo, Department of Hematology, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico
Gilberto I. Barranco-Lampon, Hematology Service, Hospital General de México “Dr. Eduardo Liceaga”, Mexico City, Mexico
Christian O. Ramos-Peñafiel, Department of Hematology, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico

Introduction: Acute lymphoblastic leukemia (ALL) is characterized by the uncontrolled proliferation of lymphoid precursor cells, most from the B phenotype, which is the result of various cytogenetic mutations and alterations involved in cell division and survival. Objective: To evaluate the efficacy of bortezomib in patients with ALL through the measurable residual disease (MRD) outcome at 6 weeks (day +45) and response to induction therapy with chemotherapy in combination with a first-generation proteasome inhibitor. Material and methods: This was cross-sectional, observational, retrospective, and analytical study based on clinical records of patients diagnosed with ALL who received induction therapy plus bortezomib, from January 1, 2019, to May 31, 2024, and comparing it to a historic group. Results: Twenty patients were included, 60% (n = 12) of whom were male, with an average age of 26 years (range 18-61 years). All cases corresponded to the B phenotype, 85% were negative for BCR: ABL1, without central nervous system infiltration (CNS). After treatment initiation, the most common adverse event was anemia and thrombocytopenia (GIII-GIV) and 30% experienced grade I-II peripheral neuropathy. When compared to the historical record, the odds ratio (OR) to evaluate the treatment response with early response variables, there was no difference (confidence interval [CI] = 0.173-1.630, p = 0.206). In overall survival, there were no statistically significant differences when compared with the historical cohort, OR of 1.538 (CI = 0.502-4.748, p = 0.319). Conclusion: The addition of bortezomib to the induction chemotherapy did not show a benefit in the percentage of remissions or the proportion of MRD. It is important to continue exploring new options that can be added to this high-risk group of patients to reduce refractoriness and the proportion of early relapses.

Keywords: Acute lymphoblastic leukemia. Bortezomib. Measurable residual disease. Complete remission. Overall survival.