Chronic Myeloid Leukemia

Treatment with imatinib, a tyrosine kinase inhibitor, resulted in a continuous complete molecular response (CMR). To our knowledge, this is the first report to demonstrate the clinical and cytogenetic manifestations of BCR::PDGFRA positive myeloid neoplasm coexisting PDGFRA mutations. Furthermore, it emphasizes the effectiveness of targeted therapy and the significance of personalized management.

P2, N=69, Active, not recruiting, St. Jude Children's Research Hospital | N=140 --> 69 | Trial completion date: Aug 2025 --> Jun 2026

P2, N=25, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026

In the event of molecular relapse, carefully considered use of imatinib or nilotinib at the lowest effective dose may be employed exclusively in the second or third trimester following multidisciplinary counseling, whereas dasatinib should be avoided throughout gestation. We emphasize structured algorithms, explicit intervention thresholds, and monthly BCR-ABL1 (IS) testing, as well as collaboration with obstetrics, neonatology, and reproductive medicine, including assisted reproductive technologies. Finally, we discuss practical pathways applicable to resource-limited settings to balance maternal-fetal safety with patient values and to support informed, preference-concordant decision-making.

For resistance, assessment of BCR::ABL1 mutations is essential, and second-line agents should be chosen according to the initial TKI and mutation sensitivity. This article summarizes the criteria and timing for switching to second-line therapy and key considerations for selecting and managing second-line TKIs, and briefly reviews the evidence for asciminib and ponatinib in second-line and later settings.

In Japan, five agents-imatinib (Glivec®), dasatinib (Sprycel®), nilotinib (Tasigna®), bosutinib (Bosulif®), and STAMP inhibitor asciminib (Scemblix®)-are currently approved for first-line therapy. Looking forward, immunologic determinants of TFR and novel therapeutic approaches, including targeting CML stem cells with agents such as asciminib or demethylating drugs, may offer prospects for cure. This review summarizes the current evidence and practical considerations in selecting first-line therapy for chronic-phase CML, with a focus on optimizing long-term outcomes and advancing toward individualized and potentially curative strategies.

Outside allogeneic stem cell transplantation (ASCT), survival with conventional therapy is dismal, representing an unmet clinical need. We summarize here the data that led to approval of pemigatinib, a FGFR1 inhibitor, showing unprecedented efficacy in M/LN-FGFR1.

Patients who underwent BCR::ABL1 mutational profiling were significantly more likely to have splenomegaly, which is not included in consensus guidelines as a reason to conduct such testing. Taken together, these findings raise potential concerns about consensus guideline adherence as a means to optimize CML management for TKI resistance.

Clinically, EVI1 overexpression is one of the most robust independent indicators of poor prognosis, associated with therapy resistance and reduced overall survival. This review provides a detailed discussion of the mechanisms underlying EVI1's activation, its complex molecular functions in hematopoietic transformation, and its profound clinical implications in hematological malignancies.

TFR patients exhibited distinct enrichment in complement and coagulation cascades (C3, C4B, F9, F11) and metabolic pathways. Plasma EV proteomes reflect CML clinical status, revealing immune and cytoskeletal alterations associated with treatment response, remission, and resistance, suggesting potential biomarkers for disease monitoring.

P2, N=60, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Jan 2028 --> Mar 2029 | Trial primary completion date: Feb 2026 --> Apr 2027

Currently, most leukemias are effectively treated with immunotherapies (highly effective monoclonal antibodies targeting CD19 [blinatumomab], or CD22 [inotuzumab ozogamicin]), BCR::ABL1 tyrosine kinase inhibitors (TKIs; e.g., dasatinib, ponatinib), Bruton TKIs (e.g., ibrutinib, acalabrutinib), BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, olutasidenib, and enasidenib), FLT3 inhibitors (e.g., midostaurin, quizartinib, and gilteritinib), menin inhibitors (revumenib, ziftomenib), and chimeric antigen receptor T-cell therapies. Herein, we provide a high-level overview of prominent clinical developments across all leukemias. In contemporary times, harnessing the benefits of novel targeted therapies and the evolving treatment landscape bolster the optimistic view that most, if not all, leukemias are curable.