Outcome for Adolescents and Young Adults (AYA) with the Hyper-CVAD (with or without Rituximab) Regimens for De Novo Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma.
Authors: Thomas Deborah A. , Rytting Michael , O'Brien Susan , Faderl Stefan , Wierda William G. , Franklin Anna , Garris Rebecca , Ravandi Farhad , Cortes Jorge , Kantarjian Hagop M. 
Published: October 2019

Abstract
Abstract 3084
Poster Board III-21
AYAs aged 16–20 yrs with de novo ALL or LL have superior outcomes when treated with intensive pediatric regimens; event-free survival rates range from 60–70% compared to 30–40% after conventional adult chemotherapy [Stock W, Blood 112:1646, 2008]. This is in part attributed to higher dose intensity (and cumulative dose) of the anthracycline, vincristine [VCR], corticosteroid and asparaginase components. The intensive hyper-CVAD regimen (fractionated cyclophosphamide, VCR, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) was originally modeled after childhood therapy for Burkitt lymphoma, and had been applied as frontline adult ALL therapy without age restriction since 1992. In contrast to conventional adult or pediatric ALL regimens, asparaginase is not administered during induction or consolidation phases. Modifications to the regimen have included the addition of rituximab for CD20 positive precursor B-cell ALL owing to adverse influence of CD20 expression, particularly in the younger subgroup [Thomas D, Blood 113:6330, 2009]. An adapted augmented Berlin-Frankfurt-Munster (BFM) regimen modeled after the CCG experience was developed specifically as frontline therapy for adolescents and adults up to age 30 in lieu of the hyper-CVAD regimen at our institution; accrual is ongoing. We updated the previous comparative hyper-CVAD experience in this young adult subset. One hundred seventy-six pts aged 13 to 30 yrs (median 22 yrs) with de novo ALL (n=149) or LL (n=27) were treated with hyper-CVAD (n=96) or modified hyper-CVAD (25 with anthracycline intensification, 55 without; 32 overall with rituximab). Eighty-three (47%) were less than 21 years of age (median 19 yrs). Forty-nine (29%) were CD20 positive. Overall complete remission (CR) rate was 97%; overall 3-yr CR duration (CRD) and survival (OS) rates were 65% and 70%, respectively. Rates for 3-yr CRD and OS were 68% and 75% if age 21 yrs or less, compared with 60% and 66%, respectively, if age 22 to 30 yrs (p=NS). The addition of rituximab improved the 3-yr CRD rates from 26% to 65% (p=.001) and 3-yr OS rates from 47% to 75% (p=.05) for the CD20 positive precursor B-cell ALL subsets, partly accounting for the improvement in outcomes. There were no significant differences in outcome by regimen for the CD20 negative subsets (all 3-yr rates > 70%). Outcomes with the hyper-CVAD regimens in AYAs appear to more closely resemble those of the pediatric approaches than the conventional regimens; incorporation of pegylated asparaginase and intensification of vincristine/corticosteroids (e.g., augmented hyper-CVAD) may further improve the efficacy of this regimen in the frontline setting. Incorporation of rituximab or the novel CD20 antibodies such as ofatumumab into the pediatric regimens warrants consideration.

Disclosures
No relevant conflicts of interest to declare.