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Pediatric-inspired ALL therapy in adults age 18-60
components of frontline therapy for B-cell ALL/LBL and may facilitate faster achievement of MRD negativity.36,37 Incorporating other new agents, such as venetoclax, into this therapeutic backbone may further enhance efficacy and increase rates of MRD negativity post-induction I.
This study has several limitations, foremost being its small size. Samples for central MRD review were avail- able for most, but not all patients, and local MRD was not considered in the primary analysis herein. While stan- dardized criteria for pegaspargase toxicity monitoring and management were provided, institutional practices in this multi-center study likely varied slightly nonetheless. During the conduct of this study, comprehensive genom- ic profiling of ALL at time of diagnosis, including assess- ment for targetable alterations characteristic of “Ph-like” ALL, became more common practice.38 Such profiling was performed inconsistently in the course of this study, lim- iting our ability to define the incidence of Ph-like ALL or overall mutational landscape in this cohort. While FACS is a powerful tool for MRD assessment with rapid results, monitoring for the malignant clonal T-cell receptor or immunoglobulin heavy chain re-arrangement by next- generation sequencing may have provided even more sensitive detection of MRD. Finally, long-term follow-up remains limited.
In summary, a pediatric-inspired regimen including pegaspargase 2,000 IU/m2 in each of six blocks of inten- sive therapy, timed to avoid overlapping toxicities, and omitting two myelosuppressive courses of consolidation, resulted in manageable toxicity, high rates of MRD nega- tivity following two-phase induction, and promising long-term efficacy in adults up to aged 60 years with newly-diagnosed ALL/LBL. The addition of active novel agents to such a regimen may increase rates of early MRD negativity and reduce rates of relapse.
Disclosures
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 fund- ing 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.
Contributions
MBG performed the research, including providing care for patients enrolled to the study, analyzed the results, and wrote the paper; EKR, AVR and PM performed the research, including providing care for patients enrolled to the study; SV, MS, and JMS gathered and managed the data; MR and QG performed the research and analyzed the results; JF, MH and SMD ana- lyzed the results; MST, DD and JHP designed and performed the research, including providing care for patients enrolled to the study, analyzed the results, and wrote the paper. All authors crit- ically reviewed the paper.
Acknowledgments
The authors thank Jessica Wardrope for assistance with organizing and compiling the centralized flow cytometric mini- mal residual disease analysis reports and thank Dr. Michael Borowitz for providing details of the Johns Hopkins University flow cytometric minimal residual disease analysis methods.
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.
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