Pb1742: feasibility and efficacy of a peg-asparaginase-based treatment protocol in elderly philadelphia-negative acute lymphoblastic leukemia patients

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Treatment of elderly Acute Lymphoblastic Leukemia (ALL) (> 60 years) is a major clinical challenge. Patients do not tolerate intensive multi-agent chemotherapy with a high therapy-related mortality (~30%) mainly due to infections. To limit toxicity, elderly patients are treated with reduced-intensity protocols that however fail to provide adequate efficacy. The use of high-dose PEG-asparaginase (PEGASP) in older patients is debated, as this population has been shown to have an increased risk of complications due to the high rate of comorbidities and multiple concomitant therapies. Aims: To explore the feasibility and efficacy of reduced toxicity induction chemotherapy combined with early and intensive PEGASP administration in elderly (>60 years) patients with Philadelphia negative ALL. Methods: Patients received reduced induction chemotherapy with PEGASP administration at 2000 UI/sqmm (max 3750 UI) on day 10 and 24 (1500 UI/sqm if age> 65 yrs, 1000 UI/sqm if age> 70 yrs) followed by 8 consolidation cycles, 4 of them including PEG-ASP in association with high-dose methotrexate. Two years maintenance or stem cell transplantation (SCT) was planned according to minimal residual disease (MRD) status. MRD was assessed by flow cytometry (MFC) and RT-PCR for JH rearrangements (MOL), after induction (TP1) and before each consolidation cycle. Results: Since 2018, 11 elderly ALL patients were enrolled, 9 had B-ALL and 2 had T-ALL (one early-T phenotype). Median age was 65 years (range 53-73). Most patients had relevant comorbidities upon enrollment (10/11, 91%): cardiac in 4, active HIV infection in 2, previous HCV and HBV in 1, previous chemotherapy for solid tumor in 1 patient. Two patients died due to infections before response assessment. CR rate after cycle 1 was 8/11 (72%). MFC was negative at TP1 in 6/8 (75%) responding patients, whereas MOL was negative in 4/8 patients (50%). All except one patient were able to achieve MOL and MFC MRD negative during consolidation phases. Most responding patients were subsequently able to proceed with the planned consolidation courses, with a median of 7.5 courses administered/8 planned. Patients received a median cumulative dose of 6300 UI/sqm of PEG-ASP, with median of 4 administrations. One high risk patient proceeded to SCT at the end of the program. Overall, PEG-ASP related toxicity was acceptable, and was mostly asymptomatic increase in bilirubin (grade IV in 2 patients, grade III in 6) or liver enzymes (grade IV in 1 patient, grade III in 7). After a median follow up of 39 months (CI 95%: 23.4-46.1), one of the 8 patients relapsed and subsequently died, 4 patients died while in MRD negative remission, one due to SARS Cov-2 infection and 3 due to other infections. All other patients are alive and in a MRD negative status. 3-year OS in the whole cohort was 38% (median 21 months). Summary/Conclusion: Data from our real-life experience demonstrate the feasibility and acceptable tolerability of the intensive and early use of PEG-ASP associated to antimetabolic therapy in elderly ALL patients, despite relevant comorbidities. With the limit of the small sample size, we observed encouraging CR and MRD negativity rate at the end of induction phase. Infectious represent leading cause of death, in this view the incorporation of novel targeted drugs may further improve the outcome.Keywords: Elderly, ALL, Minimal residual disease (MRD), Asparaginase