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B-cell acute lymphoblastic leukemia is frequent in Hispanic adolescents and young adults. Outcomes of implementation of pediatric-inspired regimens in low-and middle-income countries are not well known.In this study we treated 94 adolescents and young adults with a local BFM regimen designed to be affordable with the use of native L-asparaginase and mitoxantrone administered in an outpatient fashion, and the of BCR/ABL and measurable residual disease (MRD) determined by high sensitivity flow cytometry for risk stratification.Induction mortality was 11%; 25% of patients had to abandon treatment or be transferred to another health system. Two-year overall (OS) and event free survival (EFS) were 61.5% and 49.8%, MRD-negative patients had a 24-month OS of 85.6% vs. 69.6% (p = .024) and EFS of 76% vs. 45.5% (p = .004). Patients older than 40 years and those who abandoned treatment had worse EFS. Overall drug costs in our regimen were 52% lower than those of CALGB10403. The treatment of AYAs with ALL with an outpatient focus was implemented successfully at a reduced cost. Genetic risk assessment, treatment abandonment and lack of access to novel therapies remain major barriers for improving outcomes.

Introduction Pediatric inspired regimens can achieve good outcomes in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) by delivering intense non-myelosuppressive chemotherapy and are considered standard. Experience with the implementation of these regimens outside of academic centers in high-income countries is limited. Furthermore, Mexican patients (with "hispanic ethnicity") have increased risk for relapse and treatment related complications. Objectives Primary objective: to determine 2-year overall survival (OS) and event-free survival (EFS). Secondary objectives: to determine the impacts of treatment abandonment and measurable residual disease (MRD) on outcomes, and to compare treatment costs with a widely used standard regimen in the United States. Patients and Methods Consecutive patients 16-45 years diagnosed with Ph-negative B-cell acute lymphoblastic leukemia after 2016 were included. The salient features of our modified-BFM regimen include the use mitoxantrone, E. coli L-asparaginase, without systemic cytarabine or high dose methotrexate designed to be delivered entirely in an outpatient basis for maximum affordability (Table 1), given that we treat an uninsured population that must cover their own treatment costs out of pocket. Genetic risk assessment was limited to BCR/ABL. Thereafter, relapse risk assessment was based exclusively on "next generation" flow cytometry measurable residual disease (MRD) after consolidation, with a planned allogeneic transplant for MRD-positive patients (≥0.001%). Treatment abandonment was defined as a missed ≥14-day period during intensive treatment or ≥1 month during maintenance. Statistical analysis was performed as intent-to-treat. Lastly, drugs included in our protocol were compared to those of CALGB 10403 with current local pricing in USD. Results Ninety-one AYAs have been treated, 47 women and 44 men, with a median age of 21 years (range, 15-45), mostly with a good functional capacity and no comorbidities (ECOG≤2: 92.1%; HCT-Ci 0-1: 97.8%); 43.8% of patients had ≥30x10 9/L white blood cells at diagnosis and 31.7% had grade ≥1 obesity. Notable grade ≥3 adverse events during induction were infections/neutropenic fever (35.6%),hepatotoxicity (11%) and thrombosis/bleeding (8.1%) with 44.3% eventually requiring hospitalization. Induction related mortality was 11%. Only n=3 were refractory to induction and the remainder assessed achieved complete remission (n=63; 95.5%) with a median follow-up of 15 months (range, 0.9-50.1). N=29 received induction and consolidation entirely on an outpatient basis, ulterior hospitalizations during therapy were rare. Treatment abandonment was common (n=24; 26.4%) usually during induction (n=8; 32%) or consolidation (n=12; 48%) and mostly related to unaffordability. For the same reason, transfers to social security healthcare systems were also frequent (n=19; 20.9%). Most patients assessed were MRD negative (n=38; 74.5%) Early relapse incidence was 32.9%; 44.4% in MRD-positive and 27.5% in MRD-negative patients (p=0.43). OS at 24 months was 61.5% (95% CI 47-73%) and EFS 49.8% (95% CI 37-62%) with excellent outcomes for MRD-negative patients (Figure 1, Panels A and B). Treatment abandonment and MRD positivity were the only independent predictors of mortality in a multivariate analysis (HR 7.8 [95% CI 2.8-21.9] and HR 4.5 [95% CI 1.4-14], respectively). Lastly, the total cumulative price for medications included in our regimen was calculated at $16,750 vs. $36,061 USD in CALGB 10403, representing a cost reduction of 53.5%. Conclusions The treatment of Hispanic ALL patients with our regimen has shown promising outcomes at a reduced cost for patients. Genetic risk assessment, induction mortality, treatment abandonment and lack of access to novel therapies for MRD positive patients remain the main barriers for improving outcomes further. Figure 1 Figure 1. Disclosures Gomez-De Leon: Novartis: Honoraria; ASH: Research Funding; Sanofi: Honoraria; Abbvie: Honoraria. González López: JANSSEN: Honoraria; AMGEN: Honoraria. Gomez-Almaguer: Roche: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau.