Pediatric-Inspired Chemotherapy Incorporating Pegaspargase Is Safe and Results in High Rates of MRD Negativity in Adults Ages 18-60 with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Introduction: Among adolescents and young adults with (w/) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL), treatment using a pediatric (vs. adult) regimen appears to achieve superior event-free (EFS) and overall survival (OS); this observation has driven increased interest in adapting pediatric regimens for middle-aged adults w/ ALL/LBL. However, greater risk of toxicities associated w/ asparaginase complicates administration of pediatric-inspired regimens in adults. We therefore designed a pediatric-inspired chemotherapy regimen w/ doses of pegaspargase (PEG) rationally synchronized to limit overlapping toxicities w/ other chemotherapeutic agents. Methods: We conducted a phase II multi-center trial in adults ages 18-60 w/ newly-diagnosed Philadelphia chromosome-negative (Ph-) ALL/LBL (NCT01920737). Pts w/ Ph+ ALL or Burkitt-type ALL were ineligible. The treatment regimen consisted of 2-phase induction (I-1, I-2), followed by consolidation w/ 2 courses of alternating high-dose methotrexate-based intensification and reinduction, followed by 3 years of maintenance (Figure 1). PEG 2000 IU/m2 was administered in each of the 6 intensive courses of induction/consolidation at intervals of ≥4 weeks. Minimal residual disease (MRD) was assessed in bone marrow (BM) by multiparameter flow cytometry (FACS) on day (d) 15 of I1 and following I-1 and I-2. Any detectable MRD (even