Augmented Hyper-CVAD in Adult ALL Salvage Therapy: The MDACC Experience of Hyper-CVAD Using Dose-Intense Vincristine, Dexamethasone, and Pegaspargase.
Authors: Ayoubi Mohamad , Thomas Deborah A. , Kantarjian Hagop , O'Brien Susan , Ravandi Farhad , Garcia-Manero Guillermo , Verstovsek Srdan , Rytting Michael , Borthakur Gautam , Kadia Tapan , Kornblau Steven M. , Andreeff Michael , Feliu Jenny , Faderl Stefan 
Published: October 2019

Abstract
Abstract 2031
Poster Board II-8
Adult patients (pts) with ALL have inferior outcome compared children with a higher relapse rate and shorter disease-free survival. The prognosis remains especially poor for adults with relapsed or refractory disease. Recent studies in adolescents and young adults demonstrated better outcome when postremission therapies were intensified. Following this lead and based on our experience with hyper-CVAD (up to 8 cycles of fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine followed by maintenance therapy) we designed an augmented version of hyper-CVAD including intensified doses of vincristine, dexamethasone, and asparaginase. We have previously reported experience in 55 pts treated with augmented hyper-CVAD using L-asparaginase (Faderl et al. Blood 2007; 110: 149b). In the current extension of the trial we replaced L-asparaginase with pegaspargase, a long-acting formulation of asparaginase, which has been reported to be at least as effective and less immunogenic than L-asparaginase. With each course of hyper-CVAD and methotrexate/cytarabine, pts received vincristine 2 mg iv x 3, dexamethasone 80 mg iv/po on days 1-4 and 15-18, and pegaspargase 2,500 units/m2 iv x 1. From September 2008 until July 1009, 24 pts with relapsed/refractory ALL have been enrolled. Median age was 31 yrs (range 20-61). Nineteen pts (79%) had pre-B ALL, 4 (17%) pre-T ALL, and one pt had biphenotypic leukemia. Median number of prior regimens was 1 (range 1-4). Two pts relapsed from prior stem cell transplant (SCT). Two pts had primary refractory disease. Median remission duration to the initial induction regimen of the remainder of the pts was 37 months (range 2-78). Cytogenetics were diploid in 9 pts (38%), abnormal in 7 (29%), and not available in 8. Twenty pts are evaluable for response. Nine (45%) pts achieved CR and 7 (35%) CRp for an OR rate of 80%. Median time to CR was 34 days (range 20-80). Among the 9 CR pts, median CR duration is 3.4 months (0.4+-6.7+), CR is ongoing in 5 patients, and 6 were referred to SCT. Three pts (15%) died while on study from sepsis and myelosuppression-related complications. Neutropenic fever was common. Common non-hematologic adverse events included elevations of bilirubin and transaminases. Pegaspargase was well tolerated and had to be omitted in only 2 pts due to elevation of transaminases. No anaphylactic reactions occurred. Augmented hyper-CVAD has activity in adult patients with relapsed ALL. Pegaspargase appears to have comparable activity and less toxicity than L-asparaginase. Further studies in an adult frontline population should be considered.

Disclosures:
Faderl: Enzon: Research Funding.