Australasian Leukaemia and Lymphoma Group

Abstract ABL-rearranged (ABLr) acute lymphoblastic leukaemia (ALL) is associated with high rates of treatment failure and relapse and novel treatments are required. We investigated activity of the STAMP inhibitor asciminib in non-BCR::ABL1 ABLr ALL. The most common fusion inABLr ALL isNUP214::ABL1, which is associated with aggressive disease. For the first time we establish asciminib activity in three pre-clinical patient derived xenograft models ofNUP214::ABL1ALL. Treatment with asciminib reducedNUP214::ABL1leukaemic burden, splenomegaly and ABL1 kinase activation. We observed significantly increased survival outcomes in asciminib-treated versus control mice. Additionally, site directed mutagenesis,in vitrocell death assays andin silicostructural modeling defined a region of the ABL1 SH3 domain critical for asciminib efficacy and necessary for mediation of allosteric inhibition. Our findings establish asciminib as a potential treatment forNUP214::ABL1ALL, significantly expanding the number of ALL patients who may benefit from asciminib therapy which has an excellent safety and tolerability profile.

Topic: 35. Quality of life and palliative care Background: The CLL6 RESIDUUM trial was a joint study of the Australian Leukaemia and Lymphoma Group (ALLG) and the French Innovative Leukemia Organization (FILO) that analyzes the role of 2 years lenalidomide consolidation therapy in patients undergoing front-line treatment for CLL who do not enter MRD negative complete remission. Aims: An ancillary study of this trial aimed to assess the health-related quality of life (HRQoL) of patients with chronic lymphocytic leukemia (CLL) receiving a two year maintenance of lenalidomide (LEN) or observation (OBS) after classical immunochemotherapy leaving them with detectable minimal residual disease (MRD). Methods: Data from French patients involved in this part of the trial were used. Patients were asked to complete the EORTC QLQ-C30 version 3 questionnaire at baseline and at the end of maintenance months 3, 6, 12, 18 and 24 post randomization. Repeated measures mixed-effects models were used to assess the mean Health Related Quality of Life (HRQoL) changes from baseline to each checkpoint and for each HRQoL scale. Results: Half of the patients in each arm were over 70-year-old. Baseline data showed overall a good global health status with mean scores of 76.3 and 72.1 in the LEN and OBS arms respectively, on the 0-100 scale. At 12 months, LEN patients had significantly more diarrhea than OBS patients (p=0.003) and social functioning was significantly impaired at month 18 (p=0.05). The clinical significance of a 10-point difference appeared in the LEN arm for dyspnea and digestive disorders from month 12 on. Multivariate analysis showed a deleterious effect of LEN on global health (p=0.02) and functional scales (p=0.003). Summary/Conclusion: Supplementation with lenalidomide as maintenance therapy in CLL leads to long-term health deterioration, compared to off-therapy patients. This study provides reference HRQoL values for comparison in the developing new therapeutic approaches of CLL management. Keywords: Clinical trial, Chronic lymphocytic leukemia, Patient reported outcomes, Quality of life

[Voir la version anglaise de l’article ici : www.cmaj.ca/lookup/doi/10.1503/cmaj.220604][1] Points clés Une femme enceinte de 23 ans (2 grossesses, 1 avortement/fausse-couche, 0 parité) ayant des antécédents d’anxiété (traitée par citalopram) et d’utilisation de cocaïne (cessée avant