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Ferrata Storti Foundation
Haematologica 2021 Volume 106(8):2086-2094
Acute Lymphoblastic Leukemia
Pediatric-inspired chemotherapy incorporating pegaspargase is safe and results in high rates of minimal residual disease negativity in adults up to the age of 60 years with Philadelphia chromosome-negative acute
lymphoblastic leukemia
Mark B. Geyer,1,2 Ellen K. Ritchie,3 Arati V. Rao,4 Shreya Vemuri,5 Jessica Flynn,6 Meier Hsu6, Sean M. Devlin,6 Mikhail Roshal,7 Qi Gao,7 Madhulika Shukla,1 Jose M. Salcedo,1 Peter Maslak,1 Martin S. Tallman,1 Dan Douer1 and Jae H. Park1,2
1Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; 2Center for Cell Engineering, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; 3Weill Cornell Medical College, Hematology and Medical Oncology, Joan and Sanford I. Weill Department of Medicine, New York, NY; 4Kite-A Gilead Company, Foster City, CA; 5Sloan Kettering Institute, New York, NY; 6Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY and 7Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
ABSTRACT
Administration of pediatric-inspired chemotherapy to adults up to age 60 with acute lymphoblastic leukemia (ALL) is challenging in part due to toxicities of asparaginase as well as myelosuppression. We conducted a multi-center phase II clinical trial (clinicaltrials gov. Identifier: NCT01920737) investigating a pediatric-inspired regimen, based on the augmented arm of the Children’s Cancer Group 1882 proto- col, incorporating six doses of pegaspargase 2,000 IU/m2, rationally syn- chronized to avoid overlapping toxicity with other agents. We treated 39 adults aged 20-60 years (median age 38 years) with newly-diagnosed ALL (n=31) or lymphoblastic lymphoma (n=8). Grade 3-4 hyperbilirubinemia occurred frequently and at higher rates in patients aged 40-60 years (n=18) versus 18-39 years (n=21) (44% vs. 10%, P=0.025). However, eight of nine patients rechallenged with pegaspargase did not experience recurrent grade 3-4 hyperbilirubinemia. Grade 3-4 hypertriglyceridemia and hypofibrinogenemia were common (each 59%). Asparaginase activity at 7 days post-infusion reflected levels associated with adequate asparagine depletion, even among those with antibodies to pegaspargase. Complete response (CR)/CR with incomplete hematologic recovery was observed post-induction in 38 of 39 (97%) patients. Among patients with ALL, rates of minimal residual disease negativity by multi-parameter flow cytometry were 33% and 83% following induction phase I and phase II, respectively. Event-free and overall survival at 3 years (67.8% and 76.4%) compare favorably to outcomes observed in other series. These results demonstrate pegaspargase can be administered in the context of intensive multi-agent chemotherapy to adults aged ≤60 years with manageable toxicity. This regimen may serve as an effective backbone into which novel agents may be incorporated in future frontline studies. Trial registration: https://clini- caltrials.gov/ct2/show/NCT01920737
Introduction
Treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in children represents one of the greatest success stories in hematologic oncology and >85% of pediatric patients with ALL are ultimately cured.1
Correspondence:
JAE H. PARK
parkj6@mskcc.org
Received: March 23 2020. Accepted: September 25, 2020. Pre-published: October13,2020.
https://doi.org/10.3324/haematol.2020.251686
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