bims-hemali Biomed News
on Hematologic malignancies
Issue of 2025–06–01
fourteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Asciminib in patients with newly diagnosed chronic myeloid leukemia: results from the Japanese subgroup of ASC4FIRST.
  2. Orelabrutinib combined with rituximab and high-dose methotrexate as induction therapy in newly diagnosed primary central nervous system lymphoma.
  3. Efficacy and safety of pegylated interferon in the treatment of JAK2V617F-positive polycythemia vera with a dose de-escalation strategy: a single-center retrospective study.
  4. "Scotty, we need more power!"
  5. Dasatinib Dose Optimization Based on Therapeutic Drug Monitoring in Patients with Chronic-Phase Chronic Myeloid Leukemia.
  6. Tailor-made red cells: the long road towards blood safety.
  7. Daratumumab in Relapsed or Refractory Pediatric Immune Thrombocytopenia.
  8. Mantle Cell Lymphoma: Optimal Treatment With Bruton Tyrosine Kinase-Targeted Approaches.
  9. "Dexamethasing" acute myeloid leukemia: new opportunities for an "old" drug.
  10. OCT4 and Nestin Expression in the Microenvironment of Primary Central Nervous System Lymphomas.
  11. Neddylation status determines the therapeutic sensitivity of tyrosine kinase inhibitors in chronic myeloid leukemia.
  12. Peripheral Blood Flow Cytometry-based Definition of Plasma Cell Leukemia.
  13. [Efficacy and safety of zanubrutinib in treating refractory/relapsed warm autoimmune hemolytic anemia].
  14. Unmet needs of patients with intravascular large B-cell lymphoma: three case reports and a literature review.
  1. Int J Hematol. 2025 May 26.
    Asciminib in patients with newly diagnosed chronic myeloid leukemia: results from the Japanese subgroup of ASC4FIRST.
    Naoto Takahashi, Yoshikane Kikushige, Hirohisa Nakamae, Tatsunori Goto, Akihiro Tomita, Michiko Ichii, Satoshi Ito, Takanori Teshima, Keita Kirito, Takayuki Ikezoe, Kaoru Hatano, Hirokazu Tanaka, Nobuhiro Hiramoto, Ryohei Osako, Makoto Aoki, Kamel Malek, Yasunori Ueda.
       INTRODUCTION: The phase III ASC4FIRST study (NCT04971226) demonstrated superior efficacy and favorable safety and tolerability for asciminib against investigator-selected tyrosine kinase inhibitors (IS-TKI) in newly diagnosed chronic myeloid leukemia (CML). Results of a subgroup analysis in Japanese patients are presented here.
    METHODS: Adult patients were randomized 1:1 to asciminib or IS-TKI following stratification by European Treatment and Outcome Study long-term survival risk score and prerandomization-selected TKI (imatinib and second-generation [2G] TKI strata). At week 48, major molecular response (MMR) rate in all patients and imatinib stratum (primary endpoints) were assessed along with MR4.0, MR4.5, and safety (cutoff: November 28, 2023).
    RESULTS: In Japanese patients (asciminib, n = 21; IS-TKI, n = 17 [imatinib/2G TKI, n = 8/9]), the MMR rate was higher with asciminib (81.0%) than IS-TKI (47.1%), and versus imatinib (asciminib: 100%; imatinib: 25.0% [imatinib stratum]). More patients on asciminib than IS-TKI achieved MR4.0 (57.1% vs. 11.8%) and MR4.5 (28.6% vs. 5.9%). Fewer grade ≥ 3 adverse events (AEs; 42.9%, 50.0%, and 55.6%) and AEs leading to treatment discontinuation (0%, 37.5%, and 11.1%) occurred with asciminib than imatinib or 2G TKI.
    CONCLUSION: Outcomes in Japanese patients were consistent with the ASC4FIRST overall population. Asciminib may be a therapy of choice for Japanese patients with CML.
    Keywords:  Asciminib; CML; First-line; Japanese; TKI
    DOI:  https://doi.org/10.1007/s12185-025-04014-z
  2. Invest New Drugs. 2025 May 27.
    Orelabrutinib combined with rituximab and high-dose methotrexate as induction therapy in newly diagnosed primary central nervous system lymphoma.
    Xi-Bin Xiao, Yi-Qin Weng, Hua-Wei Jiang, Xian Li, Jing Xie, Chang-Qian Bao, Wen-Bin Qian.
       OBJECTIVE: Limited treatment options for primary central nervous system lymphoma (PCNSL) highlight the need for alternative therapies. This study evaluated orelabrutinib (O) and rituximab (R), plus high-dose methotrexate (M) (ORM), as a potential induction therapy for newly diagnosed PCNSL.
    METHODS: Patients received six cycles of 150 mg/day orelabrutinib, 375 mg/m2 rituximab, plus 3.5 g/m2 methotrexate every 3 weeks, followed by autologous hematopoietic stem cell transplantation and orelabrutinib maintenance. The primary endpoint was the overall response rate (ORR) at the end of induction therapy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
    RESULTS: From October 21, 2020, to October 22, 2024, 28 patients were treated and evaluated for efficacy and safety analyses. At the end of induction therapy, the ORR was 71.4% (95% CI, 51.3-86.8), including 16 (57.1%) complete and 4 (14.3%) partial responses. At a median follow-up of 21.6 months, the median PFS was 35.3 months (95% CI, 8.4-not evaluable), and the median OS was not reached, with PFS and OS rates of 64.3% and 96.3% at 1 year, 64.3% and 90.9% at 2 years, and 45.9% and 82.7% at 3 years, respectively. All 28 (100%) patients experienced treatment-related adverse events (TRAEs) of any grade. Grade 3 TRAEs occurred in seven (25.0%) patients, including five (17.9%) leukopenia, one (3.6%) thrombocytopenia, and one (3.6%) diarrhea. No other Bruton's tyrosine kinase inhibitor-related off-target toxicities (e.g., atrial fibrillation/flutter) or TRAE-related deaths were observed.
    CONCLUSION: The ORM induction regimen showed anti-tumor activity with a favorable safety profile, offering a potential therapeutic strategy for newly diagnosed PCNSL.
    CLINICAL TRIAL REGISTRATION:  ClinicalTrials.gov: NCT05600660.
    Keywords:  Induction therapy; Methotrexate; Orelabrutinib; PCNSL; Primary central nervous system lymphoma
    DOI:  https://doi.org/10.1007/s10637-025-01548-1
  3. Front Oncol. 2025 ;15 1586839
    Efficacy and safety of pegylated interferon in the treatment of JAK2V617F-positive polycythemia vera with a dose de-escalation strategy: a single-center retrospective study.
    Long Chang, Wen-Xin Li, Hao Cai, Jian Li, Ming-Hui Duan.
       Introduction: Although pegylated interferon (PEG-IFN) has been widely used in the treatment of polycythemia vera (PV), there is still a significant variability in its specific dosage and administration.
    Methods: This single-center retrospective study assessed the efficacy and safety of PEG-IFN in JAK2V617F-positive PV patients using a dose de-escalation strategy.
    Results: From 2018 to 2022, 110 PV patients received PEG-IFN treatment and monitored for JAK2V617F variant allele frequency (VAF) over 12 months, with 95.4% achieving complete hematological response (CHR) and 70.8% and 71.8% achieving molecular response (MR) according to the ELN2009 and 2013 criteria respectively. Patients with increased Immunoglobulin level after treatment seemed to have a higher MR rate according to the ELN2013 criteria, but the statistical difference was not significant. According to the 2013 criteria, patients with a baseline JAK2V617F VAF ≥75% had a significantly lower MR rate, and those who achieved MR had a significantly lower neutrophil-to-lymphocyte ratio (NLR) after 3 months of treatment. Although 98.2% patients experienced laboratory adverse events, only 6 patients stopping due to adverse reactions.
    Discussion: The study found that initiating PEG-IFN at 180ug weekly and adjusting only for adverse events was well-tolerated and may offer superior outcomes to traditional dosing strategies. The 12-month hematological and molecular efficacy were promising, suggesting this approach has the potential to improve long-term survival in PV patients, although further research is needed to confirm these findings.
    Keywords:  JAK2v617F mutation; dose de-escalation strategy; hematological and molecular response; pegylated interferon; polycythemia vera
    DOI:  https://doi.org/10.3389/fonc.2025.1586839
  4. Blood. 2025 May 29. 145(22): 2540-2541
    "Scotty, we need more power!"
    Kelvin Lee.
      
    DOI:  https://doi.org/10.1182/blood.2025028349
  5. Drug Des Devel Ther. 2025 ;19 4311-4320
    Dasatinib Dose Optimization Based on Therapeutic Drug Monitoring in Patients with Chronic-Phase Chronic Myeloid Leukemia.
    Fang Cheng, Zheng Cui, Qiang Li, Liu Wang, Yu Zhang, Weiming Li.
       Background: Although a dosage decrease regimen for chronic phase chronic myeloid leukemia (CML-CP) has been suggested, there is a marked lack of guidance on individualizing medication dosages for patients.
    Methods: Our aim was to explore the application of therapeutic drug monitoring (TDM) as a strategy for optimizing dasatinib dosage in patients with CML-CP.
    Results: It was observed that patients administered a dosage of 100 mg exhibited significantly higher concentrations than those given 50 mg, with no marked difference in concentration between branded and generic drugs. Further analysis unveiled a robust correlation between peak concentration (Cmax) and clinical response (major molecular response (MMR): 103.8 ± 54.0 ng/mL versus 48.6 ± 13.9 ng/mL, P < 0.001; deep molecular response (DMR): 112.7 ± 57.6 ng/mL versus 66.2 ± 36.1 ng/mL, P = 0.001). Patients with a Cmax >51.85ng/mL were more likely to achieve MMR, while those with a Cmax surpassing 112.5 ng/mL had a higher probability of attaining DMR. We successfully implemented dasatinib dose reduction based on concentrations without loss of DMR in 22 patients undergoing first-line therapy. Moreover, trough concentrations (Cmin) >2.48 ng/mL were closely associated with the onset of pleural effusion. Older patients demonstrated higher Cmin and Cmax, irrespective of whether they were on a 50 mg or 100 mg dosage regimen.
    Conclusion: TDM-based dose optimization could lead to beneficial clinical outcomes for patients with CML-CP. Furthermore, in terms of blood drug concentration, our findings supply additional evidence supporting the first-line treatment regimen of 50 mg daily.
    Keywords:  chronic myeloid leukemia; clinical response; dasatinib; dose optimization; therapeutic drug monitoring
    DOI:  https://doi.org/10.2147/DDDT.S521260
  6. Haematologica. 2025 May 29.
    Tailor-made red cells: the long road towards blood safety.
    Aleksandar Mijovic.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2025.287882
  7. N Engl J Med. 2025 May 29. 392(20): 2069-2071
    Daratumumab in Relapsed or Refractory Pediatric Immune Thrombocytopenia.
    Ting Sun, Yunfei Chen, Lei Zhang.
      
    DOI:  https://doi.org/10.1056/NEJMc2501527
  8. J Clin Oncol. 2025 May 29. JCO2500146
    Mantle Cell Lymphoma: Optimal Treatment With Bruton Tyrosine Kinase-Targeted Approaches.
    Toby A Eyre, Chan Y Cheah, Clémentine Sarkozy, Anita Kumar, Steven Le Gouill.
      Mantle cell lymphoma (MCL) represents a relatively uncommon, heterogeneous lymphoma associated with limited overall survival. Targeting of the B-cell receptor pathway in relapsed disease with covalent Bruton tyrosine kinase (cBTK) inhibition has been demonstrated to be highly effective with cBTK inhibitor monotherapy, an established standard of care in relapsed MCL. This review summarizes the recent data strongly suggesting a role for the integration of covalent BTK inhibition in the first-line treatment setting, after the recent presentation and publication of multiple phase II and randomized phase II/III clinical trials demonstrating benefit for the addition of cBTK inhibitors first line. The authors discuss herein the strength and quality of the evidence for therapeutic strategies integrating cBTK inhibitors first line and proposal treatment algorithms on the basis of assumed future availability of this highly active small molecules first line in the near future.
    DOI:  https://doi.org/10.1200/JCO-25-00146
  9. Haematologica. 2025 May 29.
    "Dexamethasing" acute myeloid leukemia: new opportunities for an "old" drug.
    Jesús Duque-Afonso, Julian List, Michael Lübbert.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2025.287404
  10. Int J Hematol Oncol Stem Cell Res. 2025 Jan 01. 19(1): 43-49
    OCT4 and Nestin Expression in the Microenvironment of Primary Central Nervous System Lymphomas.
    Ana Laura Calderón-Garcidueñas, Diana Adixa García-Trejo, Noemi Gelista-Herrera, Israel Torres-Ramírez de Arellano.
      Background: Angiogenesis is essential for the survival of neoplasms. Our aim was to describe the clinical profile of primary central nervous system lymphoma (PCNSL) patients at our institution and explore the immunohistochemical expression of OCT4 and nestin in the tumor microenvironment especially in relation to angiogenesis. Materials and Methods: All cases of PCNSL from 2016 to 2022 were retrospectively studied, and clinical and radiological characteristics of the patients were obtained. Descriptive statistics were used. Results: 26 cases were studied; 24 cases (92.3%) were B-cell lymphomas: 23 diffuse large B-cell, and one Burkitt lymphoma. 7.7 % were of T lineage. 13 women and 13 men, had age ranges between 33-71 years (mean 58.16 years). Three patients (12 %) had immunosuppression. Nestin staining revealed hypertrophic astrocytes forming patches about blood vessels with positive cytoplasmic staining in endothelium and pericytes (5-10% of the intra-tumor arterioles). These findings were seen in both B and T lymphomas. OCT4 nuclear expression was only observed in five large B-cell lymphomas and seemed to have relationship with mitoses/HPF (high power field). Conclusion: The novel finding of endothelial, pericytes and hypertrophic astrocytes staining with nestin, points to the involvement of stem cells promoting angiogenesis as a result of a dialogue between neoplastic cells and vascular stem cells. OCT4 expression seems to have a relationship with cell proliferation whose clinical significance should be investigated in prospective studies.
    Keywords:  Angiogenesis; Nestin; OCT4; Primary central nervous system lymphoma (PCNSL); T cell Lymphoma
    DOI:  https://doi.org/10.18502/ijhoscr.v19i1.17823
  11. Sci Rep. 2025 May 30. 15(1): 18978
    Neddylation status determines the therapeutic sensitivity of tyrosine kinase inhibitors in chronic myeloid leukemia.
    Congyi Zhang, Yikai Yao, Qiuting Qian, Xiongyu Han, Yunkun Lu, Xinyi Jiang, Hongqiang Cheng, Xue Zhang, Ying Chi, Yuehai Ke, Peng Xiao.
      BCR::ABL1-targeting tyrosine kinase inhibitors (TKIs) dominate the treatment of chronic myeloid leukemia (CML) over the past decades. In this study, we reported an unexpected role of neddylation inhibitors in desensitizing the therapeutic efficacy of BCR::ABL1-targeting TKIs in CML. Unlike their function in reducing drug resistance in many solid tumors, we revealed that neddylation inhibitors counteracted the cytotoxicity of TKIs against CML cells, both in cellular experiments and in animal model. Conversely, neddylation agonist sensitized the function of TKIs. RNA sequencing data revealed that neddylation inhibitor reversed the transcriptomic changes induced by TKI. Co-immunoprecipitation (co-IP) assay identified ABL1 kinase domain as a novel substrate for neddylation. Furthermore, an artificial intelligence (AI) 3-Dimensional spatial structure binding technology was employed to predict the impact of neddylation on the structure of ABL1 kinase domain. Finally, we provided potential evidence showing that TKI therapy decreased the expression of neddylation enzymes in the bone marrow of CML patients. Hence, our study offers new insights into the post-translational modification (PTM)-mediated drug resistance, and highlights the potential clinical benefits of neddylation agonists in improving the responsiveness of BCR::ABL1 TKIs in CML.
    Keywords:  Chronic myeloid leukemia; Neddylation; Post-translational modification; Resistance; Tyrosine kinase inhibitor
    DOI:  https://doi.org/10.1038/s41598-025-04153-7
  12. Leukemia. 2025 May 26.
    Peripheral Blood Flow Cytometry-based Definition of Plasma Cell Leukemia.
    Arwa Bohra, Rafla Hassan, Saurabh Zanwar, Dragan Jevremovic, Horatiu Olteanu, Wilson I Gonsalves, Gregory Otteson, Pedro Horna, S Vincent Rajkumar, Shaji Kumar.
      
    DOI:  https://doi.org/10.1038/s41375-025-02653-z
  13. Zhonghua Xue Ye Xue Za Zhi. 2025 Apr 14. 46(4): 355-358
    [Efficacy and safety of zanubrutinib in treating refractory/relapsed warm autoimmune hemolytic anemia].
    S P Shen, C Yang, M Chen, B Han.
      This retrospective analysis included 10 patients with relapsed/refractory warm autoimmune hemolytic anemia (wAIHA) who received zanubrutinib (treatment course: 3-6 months) and completed at least 3 months of follow-up at Peking Union Medical College Hospital from July 2022 to January 2024. The cohort included two male and eight female patients with a median age of 63 years (range: 36-76), who had received a median of 9 months (range: 3-22) of previous therapies. At 1-month, 3-month, and final follow-up (median 7 months), the overall response (OR) rates were 30%, 60%, and 60%, with corresponding complete response (CR) rates of 20%, 40%, and 40%, respectively. The median time to achieve a response was 2 months (range: 1-2) among the responders. No disease relapse or clonal progression was documented during follow-up. Treatment-related adverse events occurred in 30% of the patients (all grade 1-2 reversible events). One responder died of infectious multiple organ failure at 8 months after treatment initiation. Our results indicate that zanubrutinib provides rapid amelioration of anemia with manageable short-term safety in patients with relapsed/refractory wAIHA.
    DOI:  https://doi.org/10.3760/cma.j.cn121090-20241110-00442
  14. J Zhejiang Univ Sci B. 2025 May 28. pii: 1673-1581(2025)05-0493-10. [Epub ahead of print]26(5): 493-502
    Unmet needs of patients with intravascular large B-cell lymphoma: three case reports and a literature review.
    Xian Li, Ru Luo, Jiaming Xu, Xueli Jin, Weiqin Wang, Xibin Xiao, Wenbin Qian.
      Intravascular large B-cell lymphoma (IVLBCL), a rare subtype of non-Hodgkin lymphoma, is classified as an independent subtype of extranodal diffuse large B-cell lymphoma (DLBCL) in the 2008 World Health Organization (WHO) Classification (Turner et al., 2010). The 5th edition of the World Health Organization (WHO 2022) classification of hematolymphoid tumors retains this subtype (Alaggio et al., 2022). IVLBCL, which is characterized by neoplastic lymphocyte proliferation within the lumen of small blood vessels, tends to invade organs, such as the nervous system, skin, bone marrow (BM), and lung (D'Angelo et al., 2019; Satoh et al., 2019; Vásquez et al., 2019; Fukami et al., 2020).
    DOI:  https://doi.org/10.1631/jzus.B2300941
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