(041) Comparing the Safety and Efficacy of CALGB 10403 and Hyper-CVAD Induction for Acute Lymphoblastic Leukemia in Adults ≥ 40 Years Old

Poster Abstract:

Background:

Acute Lymphoblastic Leukemia (ALL) in older adult patients, although uncommon, can be challenging to treat given high- risk genetic alterations and presence of comorbidities. The CALGB 10403 regimen is a complex asparaginase based pediatric inspired regimen (PIR) for adolescents and young adults (AYA) (age 16 – 39) with ALL. Treatment outcomes have shown significant success in the AYA population with high survival rates from 80 – 90%. In contrast, treatment of adults over 40 years with ALL have lower survival rates of 30 – 40%, despite comparable complete remission (CR) rates > 90%. Asparaginase toxicities such as hypersensitivity, pancreatitis, liver dysfunction and thrombosis are often poorly tolerated by older patients. In contrast, hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) is better tolerated by adults, although with comparatively lower overall survival benefit. PIRs are typically avoided in the older adult population, however with careful monitoring they can be administered. Hence, this study is intended to add to the limited pool of data on the use of CALGB 10403 for adults ≥ 40 years old in comparison to hyper-CVAD.

Objective:

To compare safety and efficacy outcomes for CALGB 10403 compared to hyper-CVAD in adults ≥ 40 years with Acute Lymphoblastic Leukemia (ALL).

Methods:

This is a single center, retrospective study which includes patients ≥ 40 years old from January 2013 – December 2023, who either received CALGB 10403 or hyper-CVAD for induction regimen in previously untreated ALL. Information will be gathered on efficacy endpoints such as complete remission (CR), minimal residual disease (MRD), 30-day mortality, 90-day mortality, and relapse rate. Safety endpoints will include grading of peg-asparaginase based toxicities and other non-hematological toxicities from both treatment groups. Other exploratory outcomes will be reported based on significance and after completion of statistical analysis.

Results: Results pending

Conclusion: Conclusion pending

References (must also be included in final poster): 1. Aldoss I, Forman SJ, Pullarkat V. Acute Lymphoblastic Leukemia in the Older Adult. J Oncol Pract. 2019;15(2):67-75. doi:10.1200/JOP.18.00271

2. Stock W, Luger SM, Advani AS, et al. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403 [published correction appears in Blood. 2019 Sep 26;134(13):1111]. Blood. 2019;133(14):1548-1559. doi:10.1182/blood-2018-10-881961

3. Koprivnikar J, McCloskey J, Faderl S. Safety, efficacy, and clinical utility of asparaginase in the treatment of adult patients with acute lymphoblastic leukemia. Onco Targets Ther. 2017;10:1413-1422. Published 2017 Mar 6. doi:10.2147/OTT.S106810

4. Jessica Zalapa, Fausto Alfredo Rios Olais, Fernando Gil-Lopez, Analy Mora, Eduardo Gutiérrez-León, Roberta Demichelis; A Comparative Study of Hyper-CVAD and Modified CALGB-10403 Regimens in Adults with Philadelphia-Negative Acute Lymphoblastic Leukemia. Blood 2023; 142 (Supplement 1): 2833. doi: https://doi.org/10.1182/blood-2023-185323

5. Daley RJ, Rajeeve S, Kabel CC, et al. Tolerability and toxicity of pegaspargase in adults 40 years and older with acute lymphoblastic leukemia. Leuk Lymphoma. 2021;62(1):176-184. doi:10.1080/10428194.2020.1824068