Blinatumomab in the Treatment of Pediatric B-Cell Acute Lymphoblastic Leukemia Patients: Real World Experience from Mexico
Authors: Urbalejo Ceniceros Victor Itaí , Tavera Rodriguez Gabriela , Fernandez Vargas Omar Eduardo , Lopez Hernandez Gerardo , Olaya Vargas Alberto , Salazar Rosales Haydeé del Pilar , Ramirez Uribe Rosa María Nideshda , González Pedroza María de Lourdes , López-Santiago Norma , Galindo Delgado Patricia , Colunga-Pedraza Julia Esther , Cruz Garcia Carolina , Torres Girón Yessica 
Published: December 2024

Introduction
Blinatumomab, a bispecific T-cell engager antibody, has revolutionized the treatment of B-cell acute lymphoblastic leukemia (B-ALL) by targeting CD19 and CD3, triggering the death of leukemic cells. In pediatric patients, its efficacy has been demonstrated in several trials, including RIALTO and AALL1331 for relapsed/refractory (R/R) B-ALL, the AIEOP-BFM ALL 2017 trial as post-induction therapy, and a post-hoc study that explored its role in inducing measurable residual disease (MRD) negativity.
Despite these promising results, the use of blinatumomab in low- and middle-income countries (LMIC) is limited due to cost and access issues. Pediatric patients in Latin America (LATAM) also often have less favorable cytogenetic profiles, complicating treatment. Current data from LATAM are mostly from small series, underscoring the need for more comprehensive studies. To address this, we conducted a nationwide study in Mexico's main public pediatric oncology hospitals to evaluate blinatumomab use in our population.
Methods
This nationwide study included pediatric patients (aged 0-16 years) with B-ALL treated with blinatumomab. Baseline characteristics, indications, and outcomes were analyzed, with overall survival (OS) and response rates by blinatumomab indication as primary endpoints.
Results
The study included 45 pediatric B-ALL patients, with a median age at diagnosis of 5 years. Of these, 34 (75.6%) were under 10 years old, and 28 (62.2%) were male. At diagnosis, the mean hemoglobin was 7.7 g/dL, median leukocyte count was 42.75 x10^9/L, and median platelet count was 34 x10^9/L. Hypoalbuminemia was present in 30 patients, and 77.7% had elevated lactic dehydrogenase levels. Immunophenotyping showed 33.3% were CD20+, 15.6% were BCR/ABL-positive, and 4.4% had central nervous system involvement.
Induction therapy varied: 36 patients received BFM regimen, 4 St. Jude XV regimen, and 5 other regimens. Post-induction, 46.7% achieved MRD-negativity. Blinatumomab was used for R/R B-ALL in 28 patients (62.2%), for MRD-positive disease in 14 (31.1%), and in 3 (6.7%) who were MRD-negative.
Adverse events (AEs) related to blinatumomab were mainly infections, present in 42.2% of patients, including central catheter-related infections in 6 patients and neutropenic colitis in 5. Intensive care was needed for 5 patients due to cytokine release syndrome (CRS) (n=2), immune effector cell-associated neurotoxicity syndrome (ICANS) (n=2), or septic shock (n=1). CRS was reported in 53.3%, and ICANS in 11.1%, with severe (GIII/IV) cases in 3 patients each.
MRD-negativity was maintained in all initially MRD-negative patients, and achieved in 71.4% of those treated for R/R B-ALL (20 patients) or MRD-positive disease (10 patients), after a median of 2 cycles (range 1-4) of blinatumomab.
Hematopoietic stem cell transplantation (HSCT) was performed in 23 (51.1%) following blinatumomab, with 19 relapsing, including 6 post-HSCT. The median follow-up was 37 months, with 28 deaths, mainly due to progressive disease (n=18) and infections (n=9). OS at 37 months was 71%, with OS rates of 58%, 92%, and 100% for R/R, MRD-positive, and MRD-negative indications, respectively, though differences were not statistically significant (p=0.071).
Conclusions: Our study underscores blinatumomab effectivity in pediatric B-ALL patients in a LMIC setting, more commonly employed for R/R and MRD+ve disease, showing an overall MRD-negativity achievement in almost 3 of every 4 patients, even with a limited number of cycles. However, the high incidence of adverse events like CRS and ICANS requires careful management. Further research is needed to enhance safety and long-term efficacy of this novel therapy.