CAR-T therapy has transformed the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), particularly in pediatric and young adult patients. Many studies report one-year overall survival rates of between 60% and 80% following therapy. Event-free survival rates at one year are around 50–70%, with 40–50% of patients in remission after two years. Despite these impressive results, disease relapse remains a problem. Future CAR-T cell platforms should target multiple antigens, and the optimal design of such constructs must be determined. Modern trials should explore the role of CAR-T cell therapy as a consolidation treatment for patients with high-risk ALL, including those with persistent minimal residual disease at the end of induction/consolidation therapy, an IKZF1-positive gene expression profile, or a TP53 mutation or Ph-like gene expression profile. Improving the efficiency of gene-editing methods could lead to higher success rates in creating CAR-T cells, as well as reducing manufacturing time and costs. Producing universal CAR-T cells from healthy donors could significantly reduce production time and costs. These issues underscore the dynamic and evolving nature of B-ALL research. Ongoing studies and clinical trials are addressing many of these challenges in order to improve outcomes for B-ALL patients and expand the applications of CAR-T cell therapy.

Acute myeloid leukemia (AML) is an aggressive cancer with rapid progression and a high relapse rate, highlighting the urgent need for effective treatments. While recent advances in drug therapies and combination regimens have improved outcomes, relapsed and refractory (R/R) AML still shows low response rates, poor prognosis, and limited survival. The lack of effective immunotherapies further complicates the management of R/R AML. The bone marrow tumor microenvironment (TME) poses a significant barrier, requiring multifaceted, combined therapeutic strategies for clinical success. This TME creates an immunosuppressive and metabolically challenging environment that limits the expansion, persistence, cytotoxicity, and survival of chimeric antigen receptor (CAR) T cells. Unlike CD19 in B-cell acute lymphoblastic leukemia (B-ALL), AML lacks a truly leukemia-specific antigen. Although clinical trials are ongoing, no CAR-T therapies have received FDA approval for AML. This paper explores the reasons behind these ongoing challenges.

Menin inhibitors are the first targeted therapies for KMT2A-rearranged and NPM1-mutated acute leukemias, addressing a significant unmet need in these high-risk subtypes. Revumenib received approval in 2024–2025 for relapsed or refractory KMT2A-rearranged acute leukemia and NPM1-mutated AML. The AUG-MENT-101 trial reported a 23% composite complete remission rate in heavily pretreated patients, with 61% of responders achieving MRD negativity. Several menin inhibitors, including ziftomenib, bleximenib, and enzomenib, are in clinical development. They demonstrate similar efficacy, but their safety profiles differ, especially regarding QTc prolongation and coverage of resistance mutations. Combination therapies with azacitidine and venetoclax or intensive chemotherapy have achieved high response rates in newly diagnosed patients, supporting their potential use in frontline treatment. Acquired resistance, often due to MEN1 mutations at the drug-binding interface, occurs in about 40% of cases. Distinct resistance patterns among menin inhibitors suggest the possibility of sequential therapy. Approximately 30–40% of responders in relapsed or refractory trials proceeded to allogeneic transplantation, which remains a key pathway to potential cure. This review examines the molecular mechanisms of the menin-KMT2A interaction, and summarizes clinical trial data on the efficacy and safety of menin inhibitors as monotherapy and in combination.

Signaling Lymphocyte Activation Molecule Family member 7 (SLAMF7) represents a potential target for CAR T-cell therapy in the treatment of multiple myeloma (MM), and it is a promising alternative to classic BCMA-CAR therapy. The receptor is expressed on immune cells, particularly natural killer cells and T cells, that can trigger both activating and inhibitory signals. It is highly expressed in MM cells at all disease stages, playing a crucial role in cell adhesion and communication between immune cells, and being involved in the development and progression of the disease. The target has a proven clinical success with Elotuzumab (anti-SLAMF7 antibody); it works by activating immune cells to kill myeloma cells, and limited expression on normal tissues, with, potentially, few side effects. SLAMF7’s combination of specificity, stability, and clinical validation makes it an excellent target for current and future MM therapies. However, ‘fratricide death’, a phenomenon where the engineered CAR-T cells attack and kill each other, is a critical issue that requires safe engineering solutions. In this work, we will provide an overview on the field with a specific focus on SLAMF7 as an emerging CAR-T cell target in MM.

Background: Systemic mastocytosis (SM) is a clonal mast cell (MC) neoplasm driven by somatically acquired activating mutations in the KIT receptor tyrosine kinase (CD117), resulting in pathological accumulation of morphologically atypical MCs in extracutaneous organs. The KIT D816V substitution is detectable in over 95% of cases by high-sensitivity next-generation sequencing (NGS) or allele-specific PCR. This gain-of-function variant confers ligand-independent receptor autophosphorylation, leading to constitutive activation of downstream signaling cascades that promote MC progenitor survival, clonal expansion, and resistance to apoptosis. Co-occurring somatic mutations in TET2, SRSF2, ASXL1, CBL, and RUNX1, increasingly identified in the context of clonal hematopoiesis of indeterminate potential, are associated with more aggressive phenotypes and independently confer adverse prognostic impact. Results: The 2022 WHO classification delineates indolent forms from advanced-phase SM, aggressive SM, SM with an associated hematologic neoplasm (SM-AHN), and MC leukemia, which produce progressive end-organ damage through both neoplastic tissue infiltration and uncontrolled mediator release. Formal diagnosis requires integration of histological criteria (multifocal bone marrow MC aggregates of ≥15 cells), immunophenotypic aberrancies (CD25, CD2, and/or CD30 coexpression on MCs by flow cytometry or immunohistochemistry), biochemical markers (baseline serum tryptase ≥ 20 ng/mL), and molecular confirmation of KIT D816V or equivalent pathogenic KIT mutation. The development of type I KIT inhibitors with selectivity for the D816V-mutant conformation has fundamentally restructured the therapeutic field of advanced SM. Conclusions: This review provides a thorough synthesis of SM pathobiology, WHO-defined diagnostic and classification criteria, validated prognostic tools, and the developing landscape of KIT-directed and combination therapies, with direct translational relevance for specialist practitioners managing this heterogeneous myeloid neoplasm.

Background: Oral mucositis (OM) is a significant complication after allogeneic stem cell transplantation. Objectives: This prospective, observational cohort study assessed the effectiveness of a polyvinylpyrrolidone-zinc gluconate and taurine (PVP-ZG-TAU) oral gel in managing OM. The primary objective was to determine whether the gel reduced the incidence and grade of OM and accelerated its resolution. Methods: The study enrolled 82 patients; 39 received the PVP-ZG-TAU gel, and 43 represented a historical control group. To prevent oral mucositis, both groups maintained good oral hygiene. In the experimental group, patients received three sprays of PVP-ZG-TAU gel, three times a day, from the start of conditioning chemotherapy until day +15 after allo-SCT. Results: In the PVP-ZG-TAU group, 79.1% patients experienced grade 1–2 OM and 20.9% experienced grade 3–4 OM. In the control group, 74.4% had grade 1–2 OM, and 25.6% had grade 3–4 OM (p = ns). Resolution occurred significantly faster in the PVP-ZG-TAU group, with an 84% resolution rate per 100 person-weeks, compared with 62% in the control group. Cox regression analysis revealed that treatment was associated with a 68% greater likelihood of earlier resolution (adjusted hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.03–2.74; p = 0.036). Conclusions: These findings suggest that PVP-ZG-TAU can reduce OM duration and serve as a supportive intervention for allo-SCT patients.