614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Targeted Therapies

Authors Conclusion from the Abstract: Sequential combination of hyper-CVAD and blinatumomab is highly effective as frontline treatment of Ph-negative B-cell ALL, with a CR rate of 100% and 97% of pts achieving MRD negativity. Survival data are promising with an estimated 2-year OS of 86%, which compares favorably to historical controls. This study continues to accrue pts.

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

Authors Conclusion from the Abstract: The chemotherapy-free, oral combination of ponatinib, venetoclax and dexamethasone appears safe and has promising early efficacy in this heavily pretreated population of pts with R/R Ph+ ALL, with all 3 pts who received venetoclax 800mg daily achieving CMR. The MTD has not yet been reached, and the study continues to accrue.

Jeffrey E. Rubnitz, Thomas B. Alexander, Theodore W. Laetsch, et al.

Authors Conclusion from the Abstract: In this Phase 1 study, Ven with Nav and chemotherapy was well tolerated and had promising efficacy in heavily pretreated pediatric patients with ALL and LL. Given that there were four DLTs with 100 mg Nav without evidence of increased efficacy, the recommended Phase 2 dose for adult and pediatric patients is 400 mg Ven with 50 mg Nav for patients weighing ≥45 kg and 25 mg Nav for patients weighing <45 kg.

Line Stensig Lynggaard, Sofie Gottschalk Højfeldt, Lisbeth Moeller, et al.

Authors Conclusion from the Abstract: Eryaspase consistently demonstrated prolonged AEA in patients who developed hypersensitivity reactions to PEG-asp. Treatment with eryaspase was well tolerated. We conclude that eryaspase is a promising alternative to PEG-asp in case of hypersensitivity.

Authors Conclusion from the Abstract: This retrospective, multi-institutional analysis describes real world outcomes using tisagenlecleucel to treat pediatric r/r B-ALL. Early responses at 1 month and OS and EFS at 6 and 12 months are comparable to reported ELIANA trial outcomes. Safety is demonstrated in this cohort with lower rates or CRS and neurotoxicity, likely related to a lower disease burden cohort. Continued relapse and decrease in OS without evident plateau is seen following 6 months post-infusion warranting expanded follow up. Comparative analysis of outcomes in patient cohorts with varying disease burden demonstrate decreased CR, EFS and OS in patients with high disease burden as compared to patients with lower disease burden or no detectable disease at last evaluation prior to CAR infusion.

Authors Conclusion from the Abstract: In conclusion, we established first associations between DRP and clinical response for various agents providing a rationale for the evaluation of DRP in prospective clinical trials. Integration of molecular and functional information may improve the selection of more specific treatment options for patients with resistant disease. The international BFM Study Group and ITCC Consortium are planning an international multiarm early clinical trial for the treatment of r/r ALL patients that will include DRP for evaluation in order to improve the selection of targeted therapy.