612. Acute Lymphoblastic Leukemia: Clinical Studies: Novel Therapies


Nicholas J. Short, Hagop M. Kantarjian, Farhad Ravandi, Xuelin Huang, et al.

Conclusion cited from the abstract: In pts with newly diagnosed Ph+ ALL, the combination of hyper-CVAD plus ponatinib resulted in sustained responses with a CMR rate of 84% and an estimated 5-year OS rate of 73%. Among pts who did not undergo HSCT in first remission, the 3-year OS rate was 90%. Future studies are needed to determine whether the incorporation of effective novel agents such as blinatumomab into frontline regimens will allow for reduction of chemotherapy while also deepening responses and increasing the proportion of pts with Ph+ ALL who are cured without need for HSCT.

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Junfang Yang, Pengfei Jiang, Xian Zhang, Xiaobin Zhu, et al.

Conclusion cited from the abstract: Our study demonstrates safety and technical feasibility of CD19 and CD22 dual CAR-T in treating patients with CD19+CD22+ relapsed/refractory B-ALL. A low toxicity with dose-dependent high CR rate including pts who previously treated with CD19 CAR-T cells were observed. Longer observation time and more patients are needed to evaluate a beneficial advantage of the CD19/CD22 dual CAR-T over CD19 CAR-T product.

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Norman J. Lacayo, Vinod A. Pullarkat, Wendy Stock, Elias Jabbour, et al.

Conclusion cited from the abstract: Ven+Nav in combination with chemotherapy is well tolerated, with few discontinuations or dose reductions from AEs in pts with R/R ALL or LLy. The preliminary efficacy of Ven+Nav was promising in this heavily pretreated population of pts including those with prior SCT or CAR-T, with high rates of CR/CRi/CRp, and 10/18 (56%) with undetectable MRD. Additional correlative biomarker analyses are ongoing and will be presented.

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Conclusion cited from the abstract:The COG trial AALL0232, which enrolled the largest number of AYA patients to date on a pediatric B-ALL study, demonstrated significantly inferior survival and greater rates of treatment related toxicity compared to younger patients. Although treatment intensification strategies have improved outcomes in younger patients, these have not translated into the same survival benefit in those older. The higher incidence of Ph-like genomic lesions in this group of patients potentially offers a therapeutic opportunity to incorporate targeted therapies for AYA. Thus, future trials must identify novel strategies to not only improve outcomes but further reduce toxicity in the AYA cohort.

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Bachar Samra, Hagop M. Kantarjian, Koji Sasaki, Nicholas J. Short, et al.

Conclusion cited from the abstract: The lack of achievement of MMR at 3 months predicted worse outcomes in Ph+ ALL. Higher survival rates were seen when ASCT was performed in pts who do not achieve 3-month MMR. Innovative targeted strategies aimed to eradicate minimal residual disease are needed to further improve long term outcomes.

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Anthony V. Moorman, Ellie Butler, Emilio Barretta, Amy A. Kirkwood, et al.

Conclusion cited from the abstract: Collectively these data indicate that primary chromosomal abnormalities remain stronger prognostic markers in adult ALL than the more recently identified secondary deletions. On the basis of these results, we propose an amendment to the genetic risk classification for adult ALL wherein groups with distinct outcomes (see figure) comprise: (1) very high risk: CK, HoL or JAK-STAT abnormalities; (2) high risk: all KMT2A fusions; (3) Tyrosine kinase sensitive: BCR-ABL1 and ABL-class fusions; (4) low risk ZNF384 fusions; (5) standard risk: all other patients. The integration of these primary genetic risk factors with other risk factor such as age, white cell count and MRD into an overall risk score is a key goal of our current work.

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