ALL - Novel subgroups and agents

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LINKS TO ABSTRACTS:

Presentation ID p402-1

(S110) LOSS OF IKZF1 CONTRIBUTES TO CYTARABINE RESISTANCE IN B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA

Presenter: Britt Vervoort, Utrecht, The Netherlands

The study authors conclude that their results demonstrate that loss of IKZF1 confers resistance to AraC, both in experimental models and in patient-derived cells. They are currently performing CRISPR/CAS9 based reverse genetics screens to identify genes/pathways that enhance response to AraC or other antimetabolites. They expect that their approach will allow them to identify (hematopoietic cell-specific) pathways that can be targeted to sensitize responses to AraC in IKZF1 deleted ALL and possibly AML. Finally: Preclinical validations of these findings, using representative PDX models, will guide the development of more effective antimetabolite therapies for this high-risk patient group.

 

Presentation ID p402-2

(S111) REDEFINING LOW RISK HIGH HYPERDIPLOIDY IN PAEDIATRIC ACUTE LYMPHOBLASTIC LEUKAEMIA

Presenter: Anthony Moorman, Newcastle upon Tyne, United Kingdom

The study authors conclude that the UKALL-HeH profile defines two distinct HeH risk groups. Patients with a UKALL-HeH GR profile have an excellent outcome and represent a low-risk subgroup of HeH which could be considered for treatment de-escalation.

 

Presentation ID p402-3

(S112) UPDATED RESULTS OF THE GIMEMA LAL2116, D-ALBA TRIAL, FOR NEWLY DIAGNOSED ADULTS WITH PH+ ALL

Presenter: Sabina Chiaretti, Rome, Italy

The study authors conclude that in their updated analysis of the D-ALBA trial, they confirm the very favorable outcome previously reported, as well as the deleterious prognostic impact of the IKZF1-plus genotype and the low transplant-related mortality rate. Among the few relapses, they observed a rather high incidence of CNS involvement. In the upcoming trial for newly diagnosed adult Ph+ ALL, CNS prophylaxis will be increased.

 

The study authors conclude that the chemotherapy-free combination of ponatinib and blinatumomab shows encouraging safety and efficacy in Ph+ ALL, with high rates of CMR and durable remissions, particularly when used in the frontline setting. All ND patients remain in remission without HSCT, suggesting that this regimen may obviate the need for HSCT in this setting.

 

Presentation ID p402-5

(S114) PRELIMINARY RESULTS OF THE GIMEMA LAL2317 SEQUENTIAL CHEMOTHERAPY-BLINATUMOMAB FRONT-LINE TRIAL FOR NEWLY DIAGNOSED ADULT PH-NEGATIVE B-LINEAGE ALL PATIENTS

Presenter: Renato Bassan, Italy

The study authors conclude that their preliminary analysis highlights the efficacy of blinatumomab added to chemotherapy in increasing MRD negativity (<10-4) in CD19+ B-lineage Ph-ALL, with the primary study endpoint fully achieved. This effect appears to translate into a lower early relapse rate and appears detectable in all-risk subsets.