bims-hemali Biomed News
on Hematologic malignancies
Issue of 2025–07–13
eight papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Management of chronic myeloid leukemia in 2025.
  2. Targeting WEE1 and asciminib suppresses ABL-tyrosine kinase inhibitor-resistant chronic myeloid leukemia cells.
  3. How will genomic testing impact a clinician's choice for managing chronic myeloid leukemia?
  4. Subcutaneous epcoritamab monotherapy in Japanese patients with relapsed or refractory follicular lymphoma: primary results of the EPCORE NHL-3 trial.
  5. Surgical management of giant splenomegaly in chronic myeloid leukemia: a challenging splenectomy case.
  6. CSF3R mutations and variants in myeloid neoplasms: associated phenotypes, co-mutations, and survival trends.
  7. [Molecular targeted therapy for peripheral T-cell lymphoma].
  8. Recent advances in understanding and management of intravascular large B-cell lymphoma.
  1. Cancer. 2025 Jul 15. 131(14): e35953
    Management of chronic myeloid leukemia in 2025.
    Hagop Kantarjian, Massimo Breccia, Fadi G Haddad, Rüdiger Hehlmann, Ghayas C Issa, Hemant Malhotra, Franck Emmanuel Nicolini, Koji Sasaki, Leif Stenke, Elias Jabbour.
      Chronic myeloid leukemia (CML) has an annual incidence of approximately two cases per 100,000. The reduction in annual mortality from 10%-20% to 1% with BCR::ABL1 tyrosine kinase inhibitors (TKIs) has resulted in an increased prevalence in the United States of an estimated 150,000 cases in 2025. This translates into a worldwide estimated prevalence of approximately 5 million cases, and hence the need to make TKIs available and affordable to all patients. The four main goals of CML therapy are to (1) improve survival; (2) achieve a durable deep molecular response, which may lead to a treatment-free remission status; (3) reduce short- and long-term side effects; and (4) provide good treatment value. Today, the six approved BCR::ABL1 TKIs, five in frontline therapy (imatinib, dasatinib, bosutinib, nilotinib, and asciminib) and all six in later line therapy (including ponatinib), fulfill in one form or another these requirements. Third-generation TKIs that target the ABL1 kinase domain (olverembatinib and ELVN-001) or the myristoyl pocket (TGRX-678 and TERN-701) are under development. Allogeneic hematopoietic stem cell transplantation is a one-time, cost-effective, curative treatment in patients with CML resistant to second-generation TKIs, which is perhaps surprisingly underused in 2025, given the high enthusiasm for it before the development of TKIs. However, serious complications, such as graft-vs-host disease, or death could occur. This review summarizes relevant information concerning the management of CML in 2025, and addresses some CML treatment pathways that became entrenched in the management of CML in the first 15-20 years of TKI experience, which may need to be revisited.
    Keywords:  chronic myeloid leukemia (CML); cost; frontline; tyrosine kinase inhibitor (TKI)
    DOI:  https://doi.org/10.1002/cncr.35953
  2. Discov Oncol. 2025 Jul 08. 16(1): 1283
    Targeting WEE1 and asciminib suppresses ABL-tyrosine kinase inhibitor-resistant chronic myeloid leukemia cells.
    Seiichi Okabe, Mitsuru Moriyama, Akihiko Gotoh, Daigo Akahane.
       BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the uncontrolled proliferation of white blood cells. Tyrosine kinase inhibitors (TKIs) are the standard treatment; however, resistance to BCR::ABL1 mutations remains challenging. WEE1, a checkpoint kinase involved in mitosis and DNA repair, is a potential therapeutic target for CML treatment.
    METHODS: Ponatinib-resistant CML cells were screened to identify candidates for overcoming drug resistance. The efficacy of the ABL TKI asciminib and the WEE1 inhibitor MK-1775 was evaluated using proliferation and colony formation assays. Public database analysis (GSE100026) assessed WEE1/PKMYT1 expression in CML.
    RESULTS: In vitro screening identified MK-1775 as a promising therapeutic candidate. WEE1/PKMYT1 expression was elevated in CML cells compared to healthy cells. Both asciminib and MK-1775 inhibited CML cell proliferation after 72 h, with enhanced cytotoxicity when combined. Co-treatment reduced colony formation and induced G2/M arrest, whereas an increase in the sub-G1 cell population indicated apoptosis. Furthermore, the combination treatment disrupted the mitochondrial membrane potential.
    CONCLUSIONS: The combination of asciminib and WEE1 inhibition demonstrated greater efficacy than either drug alone, suggesting a novel therapeutic strategy for treating CML. These findings provide insights into overcoming TKI resistance and highlight a promising approach for future clinical applications.
    Keywords:  ABL inhibitor resistance; Chronic myeloid leukemia; STAMP inhibitor; WEE1 inhibitor
    DOI:  https://doi.org/10.1007/s12672-025-03036-7
  3. Expert Rev Hematol. 2025 Jul 10.
    How will genomic testing impact a clinician's choice for managing chronic myeloid leukemia?
    Jessica Sia, Naranie Shanmuganathan.
       INTRODUCTION: Chronic myeloid leukemia (CML) is a disease characterized by a single diagnostic molecular abnormality and epitomizes a genetically based diagnosis and management. Targeted therapy with tyrosine kinase inhibitors has revolutionized treatment and prognosis of this disease; however, a proportion of patients will experience resistance to therapy and progress to blast phase, the terminal phase of this disease. Emerging genomic profiling in CML reveals a genetically heterogenous landscape which may permit further risk stratification, personalization of treatment, and the potential for drug development.This review encompasses original literature exploring the genomic profile of CML and the potential impact of additional genomic abnormalities on prognosis and treatment response.
    EXPERT OPINION: Somatic variants in cancer-associated genes, particularly ASXL1, are of prognostic and potential therapeutic significance in CML. Up-front next-generation sequencing is therefore useful when available in all patients with newly diagnosed CML and repeat testing should be considered at timepoints of suboptimal treatment response, TKI resistance, and progression. Gene rearrangements and fusions are an emerging class of mutation that may confer adverse prognostic risk and hence use of a robust testing method that enables detection of such abnormalities is desirable.
    Keywords:  BCR:ABL1; TKI resistance; chronic myeloid leukemia; next-generation sequencing; personalized therapy
    DOI:  https://doi.org/10.1080/17474086.2025.2533235
  4. Leuk Lymphoma. 2025 Jul 09. 1-9
    Subcutaneous epcoritamab monotherapy in Japanese patients with relapsed or refractory follicular lymphoma: primary results of the EPCORE NHL-3 trial.
    Koji Izutsu, Daigo Akahane, Tomomi Toubai, Toko Saito, Yuko Mishima, Tomoaki Fujisaki, Momoko Nishikori, Takahiro Kumode, Youko Suehiro, Kenji Ishitsuka, Rebekah Conlon, Ami Takahashi, Barbara D'Angelo Månsson, Elena Favaro, Noriko Fukuhara.
      An unmet need exists for patients with relapsed or refractory (R/R) follicular lymphoma (FL) whose disease remains incurable. Epcoritamab, a subcutaneous CD3xCD20 bispecific antibody, is approved for R/R FL and different types of R/R large B-cell lymphoma after ≥2 prior lines of therapy (pLOT) in the US, Europe, and Japan. Regional data are critical to contextualize global trial data. In the Japan-specific EPCORE NHL-3 trial (phase 1/2), 21 adults with R/R FL and ≥2 pLOT received subcutaneous epcoritamab (two step-up doses, then 48-mg full doses) until progression. Median follow-up was 21.2 months. Responses were frequent and deep (overall response rate, 95.2%; complete response rate, 76.2%), including in high-risk subgroups, as well as durable. Safety was manageable; cytokine release syndrome events had predictable timing and were mostly low grade, and no fatal treatment-emergent adverse events occurred. These results support epcoritamab as a new treatment option for Japanese patients with R/R FL.Clinical trial registration numbers: NCT04542824; JapicCTI-205408; jRCT2080225312.
    Keywords:  B-cell lymphoma; CD20 antigen; CD3 antigen; bispecific antibodies; follicular lymphoma
    DOI:  https://doi.org/10.1080/10428194.2025.2525983
  5. J Surg Case Rep. 2025 Jul;2025(7): rjaf485
    Surgical management of giant splenomegaly in chronic myeloid leukemia: a challenging splenectomy case.
    Wail Alqatta.
      Giant splenomegaly is an uncommon but significant complication of chronic myeloid leukemia (CML), often causing substantial morbidity. While tyrosine kinase inhibitors have revolutionized CML treatment, splenectomy remains necessary in selected cases, particularly when there is symptomatic hypersplenism, compressive symptoms, or risk of splenic rupture. This case describes a 35-year-old male with chronic-phase CML who presented with progressive abdominal distension, early satiety, and anemia due to massive splenomegaly. Abdominal ultrasound revealed a spleen measuring 40 cm, extending into the pelvis. Despite optimized therapy, symptoms persisted. After multidisciplinary assessment and preoperative vaccination, the patient underwent an open splenectomy. The procedure, though technically challenging, was completed without complications. Histopathology confirmed leukemic infiltration of the spleen. The patient's postoperative course was uneventful, with no adverse events. This case underscores splenectomy as a viable and effective therapeutic option in selected CML patients with symptomatic giant splenomegaly.
    Keywords:  case report; chronic myeloid leukemia; giant splenomegaly; hypersplenism; splenectomy
    DOI:  https://doi.org/10.1093/jscr/rjaf485
  6. Haematologica. 2025 Jul 10.
    CSF3R mutations and variants in myeloid neoplasms: associated phenotypes, co-mutations, and survival trends.
    Abiola Bolarinwa, Natasha Szuber, Rong He, Animesh Pardanani, Naseema Gangat, Ayalew Tefferi.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2025.288026
  7. Rinsho Ketsueki. 2025 ;66(6): 456-463
    [Molecular targeted therapy for peripheral T-cell lymphoma].
    Kazuyuki Shimada.
      Peripheral T-cell lymphoma (PTCL) is a highly heterogenous disease that accounts for 10 to 15% of malignant lymphomas. It encompasses a wide range of disease types, including nodal, extranodal, and leukemic forms. Recent molecular genetic findings about PTCL have significantly deepened our understanding of the disease, leading to the reclassification of previously distinct subtypes under a unified entity (e.g., T-follicular helper lymphoma). In terms of treatment, CHOP or CHOP-like therapy have been widely adopted as a first-line regimen. However, even in ALK-positive anaplastic large cell lymphoma, which generally has favorable outcomes, the prognosis of PTCL remains unsatisfactory. The extremely poor outcomes of relapsed and refractory disease have highlighted an urgent need for breakthrough therapies. In recent years, novel therapeutic approaches, including antibody-drug conjugates, epigenetic modifiers, and immune cell therapies, have improved clinical outcomes for some patients with PTCL. However, the optimal use of novel approaches remains unclear, and stratification based on molecular genetic findings is crucial to achieve more effective and precisely targeted treatment.
    Keywords:  CD30; Epigenetic modifier drugs; Peripheral T-cell lymphoma; Targeting drugs
    DOI:  https://doi.org/10.11406/rinketsu.66.456
  8. Jpn J Clin Oncol. 2025 Jul 09. pii: hyaf112. [Epub ahead of print]
    Recent advances in understanding and management of intravascular large B-cell lymphoma.
    Kazuyuki Shimada.
      Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma characterized by the proliferation of tumor cells within the lumina of small vessels in systemic organs. Diagnosis remains challenging due to the frequent presentation of non-specific symptoms such as fever and general malaise. Since its listing as a distinct disease entity in the 4th edition of the World Health Organization classification, awareness of IVLBCL has increased, leading to improvements in diagnostic accuracy. Nevertheless, patients with delayed or difficult diagnosis continue to be reported. Recent genetic studies have identified recurrent genetic abnormalities associated with IVLBCL, and the potential utility of liquid biopsy for diagnosis and treatment monitoring has been suggested. However, despite these advances, a gap remains between translational research and clinical application, particularly regarding how liquid biopsy can be incorporated into clinical practice. Regarding treatment, although standard chemotherapy with central-nervous-system-directed therapy has demonstrated favorable outcomes in initial management, the efficacy and safety of emerging immune cell therapies in IVLBCL remain largely unknown. This article aims to review recent advances in the understanding and management of IVLBCL, with the ultimate goal of improving clinical outcomes and advancing therapeutic management of IVLBCL.
    Keywords:  R-CHOP therapy; central nervous system involvement; genetic alterations; intravascular large B-cell lymphoma
    DOI:  https://doi.org/10.1093/jjco/hyaf112
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