ABL1 T315I

P1, N=242, Recruiting, Ascentage Pharma Group Inc. | N=62 --> 242 | Trial completion date: Jan 2024 --> Mar 2030 | Trial primary completion date: Jan 2024 --> Dec 2029

The proportions of the patients with white blood cell count [14.1 (4.3, 48.9)×10⁹/L vs 50.1 (11.5, 149.0)×10⁹/L], serum lactate dehydrogenase level [510 (297, 930) vs 900 (535, 1 898) U/L], and treatment with imatinib following blast phase [8.4% (9/107) vs 20.5% (7/34)] were all lower than those in the monotherapy group (all P<0.05)...While patients receiving TKI combination therapy demonstrate higher rates of MMR, their overall survival remains poorer. Isolated extramedullary acute myeloid blast phase, and the achievement of MHR and/or DMR through treatment are beneficial for the survival of patients with CML-MBP.

There were acceptable treatment-related adverse events. We conclude olverembatinib is effective and tolerable in subjects in accelerated phase CML failing prior TKI therapy.

Combination therapies with ponatinib or other agents, as well as newer TKIs like olverembatinib, have demonstrated potential in overcoming resistance in preclinical and clinical models. Understanding these diverse resistance mechanisms is critical for optimizing asciminib-based treatment strategies and guiding the development of effective combination therapies for patients with resistant CML.

This study introduces a microfluidic cell culture array for the comparative analysis of six BCR::ABL1 TKIs, namely imatinib, nilotinib, bosutinib, ponatinib, dasatinib, and asciminib, using CML-related cell lines. We further validated the device with a CML patient-derived bone marrow sample, requiring only minimal adjustments to the experimental conditions. The proposed microfluidic single-cell-based screening array could refine treatment regimens and advance personalized medicine in CML.

Overall, most patients remained on treatment and achieved or maintained MMR, suggesting that asciminib was well-tolerated and effective. Results were consistent among subgroups, indicating that asciminib is an effective option for patients regardless of prior TKI used, and including those intolerant or resistant to their first TKI.

P=N/A, N=34, Not yet recruiting, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

She was treated with intravenous fluids, analgesia, and anticoagulation; initially with heparin infusion, later transitioned to apixaban. Concurrently, disease-directed therapy with asciminib and hydroxyurea led to a partial hematologic response...It underscores the importance of timely imaging for diagnosis and the delicate balance of anticoagulation in the setting of malignancy-associated thrombocytosis. Individualized, multidisciplinary management and careful long-term follow-up are essential to optimize outcomes in this complex patient population.

A retrospective cohort study of CML patients at Blood Transfusion Hematology Hospital who were resistant to frontline imatinib between Oct 2010 and Oct 2018...In addition, M244V, T315I, E459K, E255K, F317L, Q252H and E355G were all observed in primary resistant patients. The emergence of certain specific mutations may serve as the early indicators of leukemic progression, necessitating prompt intervention for better disease control.

Most patients (78%) received ASC as a third-line or later treatment, with 93% previously treated with ponatinib. Post-ASC mutations were analyzed in 7 relapsing patients, identifying a new Q252H mutation in 2 cases. In conclusion, our findings suggest that ASC is an effective salvage therapy for Ph+ ALL and LBC-CML.

P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

Additionally, 19 patients (33.9%) had been treated with ponatinib. The prevalent treatment-related nonhematologic adverse events, primarily classified as grade 1/2, included skin hyperpigmentation, proteinuria, increased liver enzyme levels, and hypertriglyceridemia. Olverembatinib-based therapy demonstrated significant efficacy and manageable toxicity in patients with advanced Ph+ leukemia.