612. Acute Lymphoblastic Leukemia: Clinical Studies: Insights in Genomics, MRD, and Toxicities

Judith M. Boer, Maria Grazia Valsecchi, Femke M. Hormann, et al.

Authors Conclusion from the AbstractNUTM1r ALL was identified as the second largest subtype in infants, found in 21.7% of KMT2Ar-negative infant B-ALL, representing 5-7% of total infant ALL, and associated with excellent outcome on Interfant standard risk protocols. The favorable outcome was confirmed in the Ponte di Legno cohort of infant and pediatric NUTM1r-positive patients enrolled on different treatment protocols over more than two decades. We conclude that NUTM1r ALL is a favorable genetic subtype in infants and children and possibly eligible for treatment reduction.

Nicholas J. Short, Hagop M. Kantarjian, Keyur Patel, et al

Authors Conclusion from the Abstract: Early assessment of MRD using an ultrasensitive NGS assay can identify pts with ALL who have a very low risk of relapse and excellent long-term survival. Prospective studies are warranted to assess whether de-intensification of therapy is feasible for this favorable-risk group of pts who rapidly achieve MRDneg remission.

Kelsey-Leigh A Garcia, Philip A. Stevenson, Sindhu Cherian, et al.

Authors Conclusion from the Abstract: MFC of CSF is more predictive of CNS relapse risk than CC in the context of front-line hyperCVAD, questioning the use of CC if MFC is performed. Further, CNS relapses were significantly more frequent when CSF+ despite administration of significantly more intra-CSF chemo. Traumatic LP per se did not increase risk of CNS relapse if CSF- by MFC. Surveillance during treatment by MFC in CSF- pts identified no cases of occult CNS relapse, arguing against this routine practice. Future studies should consider incorporating MFC of CSF into risk-adapted CNS-directed treatment strategies.

Line Stensig Lynggaard, Lisbeth Moeller, Cecilie Utke Rank, et al.

Authors Conclusion from the Abstract: We found no difference in the incidence of toxicities between AEA in ´therapeutic levels´ and ´high levels´ group, and there will be no clinical advantage in using TDM to identify patients with high AEA-levels for dose adjustment. The significantly lower incidence of asp-tox in patients without AEA and AEA-levels <100 UI/L reflects the high proportion of hypersensitivity patients with inactivation of asparaginase and supports that the efficacy of asparaginase treatment is insufficient for these patients.

Lynda M. Vrooman, Yael Flamand, Victoria Koch, et al.

Authors Conclusion from the Abstract: Fifty percent of pts with a Grade 2 reaction to pegaspargase were able to tolerate and achieve adequate SAA when re-challenged with premedication. For those who did react with or after re-challenge, reactions were not more severe. The re-challenge approach limits premedication exposure only to a minority of pts with a history of prior reaction and substantially decreases the number of pts needing to switch to Erwinia asparaginase, which can be challenging to deliver due to administration schedule and drug shortage.

Yannis K. Valtis, Kristen E. Stevenson,  Andrew E. Place, et al.

Authors Conclusion from the Abstract: In a large cohort of AYA ALL pts aged 15-50 yrs treated on a pediatric regimen, orthopedic toxicities were common (17% for ON, 12% for fx at 5 yrs). Younger pts (< 30 yrs) experienced higher rates of ON, as well as pts treated on later-generation PEG-asp protocols which combined dex and PEG asp. Increased rates of orthopedic toxicity in later generation protocols may be driven by the pharmacokinetic drug interaction between PEG asp and dex, leading to higher dex exposure (Yan JCO 2008, Panetta Clin Pharmacol Ther 2009). Increased awareness may be useful in early identification of orthopedic toxicities. Future efforts should focus on further understanding the pathophysiology and risk factors for orthopedic toxicity in ALL AYA regimens and developing prophylactic interventions.