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 protocol, incorporating six doses of pegaspargase 2,000 IU/m2, rationally synchronized 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2086-2094 |
| Number of pages | 9 |
| Journal | Haematologica |
| Volume | 106 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2021 |
Funding
Research support was provided by Servier Pharmaceuticals. MBG received funding from Lymphoma Research Foundation, American Society of Hematology, MSK Comedy versus Cancer Grant, Nancy and Jeffrey Heller Giving Fund; JHP received funding from Conquer Cancer Foundation of ASCO, Leukemia and Lymphoma Society Career Development Grant, The Geoffrey Beene Cancer Foundation, National Comprehensive Cancer Center Young Investigator Award, and American Society of Hematology Scholar Junior Faculty Award. MBG has received research support from Amgen; EKR sits on the advisory board of Agios, Celegne, Genetech, Pfizer and Tolero, has received travel support from Celgene, Novartis and Pfizer, has received research funding from Bristol-Myers Squibb, NS Pharma, Jazz Pharmaceuticals, Novartis, Astellas and Pfizer, consults for Celgene, Novartis, Pfizer and Incyte, is part of the speakers’ bureau of Pfizer, Novartis, Incyte and Ariad; AVR is employed by Kite; DD consults for Servier Pharmaceuticals and Amgen, is part of the speakers’ bureau of Servier Pharmaceuticals, Amgen and Adaptive Biotech, and consults for Servier Pharmaceuticals and Amgen; MST sits on the advisory board of Daiichi, Oncolyze, Tetraphase, Jazz Pharmaceuticals, Rigel, KAHR, Abbvie, Nohla, Orsenix, Delta Fly Pharma, BioLineRx and Roche, has received research funding from Cellerant, Biosight, ADC Therapeutics and Abbvie, has patents and royalties at UpToDate, and consults for Daiichi-Sankyo, Oncolyze, Tetraphase, Jazz Pharmaceuticals, Rigel, KAHR, Abbvie, Nohla, Orsenix, Delta Fly Pharma and BioLineRx; JHP has received research funding from Juno Therapeutics and Genentech/Roche, has a consultancy advisory role at Amgen and Juno Therapeutics, and consults for Kite, Incyte, GSK, Autolus, AstraZeneca, Allogene, Novartis, Takeda, Servier and Intellia.
ASJC Scopus subject areas
- Hematology
