bims-hemali Biomed News
on Hematologic malignancies
Issue of 2025–11–02
24 papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. SOHO State of the Art Updates and Next Questions | Choosing the Best Frontline BCR::ABL1 Tyrosine Kinase Inhibitor in Chronic Myeloid Leukemia-How to Define the Treatment Value?
  2. Treatment of chronic myeloid leukemia chronic phase patients in third-line setting and beyond: recommendations from a Belgian expert panel in 2025.
  3. Outcomes of patients with relapsed or refractory primary mediastinal B-cell lymphoma after frontline DA-EPOCH-R.
  4. Pediatric chronic myeloid leukemia: A decade of clinical experience at the NBK specialized hospital for children.
  5. Bing-Neel Syndrome in Waldenström Macroglobulinemia: Updates on Clinical Management and BTK Inhibitor Efficacy.
  6. ReXPOsing a weakness in TP53-mutant MDS and AML.
  7. Final safety and efficacy results from a phase 1/2 study of tagraxofusp, a CD123-targeted therapy, for myelofibrosis.
  8. A retrospective analysis of clinicopathological and genetic features of synchronous CNS and systemic DLBCL at diagnosis.
  9. ctDNA dynamics demonstrates rapid treatment response to tafasitamab + R-CHOP +/- lenalidomide and predicts outcome in diffuse large B-cell lymphoma: results from the phase 1b First-MIND study.
  10. Effective Treatment with Ruxolitinib and Ropeginterferon Alfa-2b for Refractory TAFRO-like Syndrome.
  11. A Retrospective Study of Treatment and Outcomes in Synchronous Systemic and Central Nervous System Large B-cell Lymphoma.
  12. Decitabine-cedazuridine in patients with MDS and TP53 mutations.
  13. Retreatment with R-CHOP-like Therapy in Patients with Late Relapse of Diffuse Large B-Cell Lymphoma.
  14. Nivolumab with doxorubicin, vinblastine, and dacarbazine for the frontline treatment of central nervous system classical Hodgkin lymphoma.
  15. Using a Novel Consensus-Based Chemoinformatics Approach to Predict ADMET Properties and Druglikeness of Tyrosine Kinase Inhibitors.
  16. Bispecific antibodies in action: the reality of engagement.
  17. NPM1 mediated up - regulation of CXCR4 might drive bortezomib resistance in multiple Myeloma.
  18. Novel Molecular Insights and Evolution of Less Toxic Therapeutic Strategies in Burkitt Lymphoma.
  19. Andexanet alfa for the reversal of the low-molecular-weight heparin enoxaparin.
  20. High-grade/large B-cell lymphoma-11q has a very good prognosis in children and young people without a predisposition.
  21. Progress in the Treatment of Advanced-Stage Classical Hodgkin Lymphoma in the PET-Adapted Era.
  22. Long-term Efficacy and Safety of Ropeginterferon Alfa-2b under its HIDAT Regimen for the Treatment of Polycythemia Vera.
  23. Plain language summary about tirabrutinib in relapsed/refractory primary central nervous system lymphoma.
  24. Granulocyte colony-stimulating factor plus venetoclax and azacitidine in newly diagnosed acute myeloid leukemia: a multicenter phase 2 trial.
  1. Clin Lymphoma Myeloma Leuk. 2025 Oct 04. pii: S2152-2650(25)04228-4. [Epub ahead of print]
    SOHO State of the Art Updates and Next Questions | Choosing the Best Frontline BCR::ABL1 Tyrosine Kinase Inhibitor in Chronic Myeloid Leukemia-How to Define the Treatment Value?
    Fadi G Haddad, Elias Jabbour, Massimo Breccia, Rüdiger Hehlmann, Hemant Malhotra, Franck Emmanuel Nicolini, Leif Stenke, Hagop Kantarjian.
      Over the last 2 decades, progress in research, treatment approaches, and market dynamics have influenced our treatment of chronic myeloid leukemia in chronic phase (CML-CP). The choice of frontline therapy depends on the treatment goal (normalizing survival only or achieving a treatment-free remission [TFR]), the toxicity profile of each BCR::ABL1 tyrosine kinase inhibitor (TKI), the patient's comorbidities, and the cost and affordability of the treatment. When overall survival is the aim of therapy, generics of imatinib and of second-generation BCR::ABL1 TKIs offer an excellent treatment value. For patients with high-risk CML-CP or those aiming for TFR, second-generation TKIs might be the optimal frontline strategy. Challenges persist in ensuring universal access to therapy, particularly for patients in poorer conditions or geographies. With cost-effective generics now accessible, all patients with CML-CP should have the opportunity to receive imatinib (price < $1000/year worldwide), and most can have access to safe and effective second-generation TKIs. This still may not be possible in the United States and in other nations where second-generation TKIs, even generics, are still too expensive and of poor "treatment value." Strategies such as dose optimization can enhance the TKI affordability without compromising efficacy, particularly for elderly or low-risk patients. For a novel TKI to become established frontline therapy, it should improve the durable deep molecular response rate (BCR::ABL1 transcripts on the International Scale < 0.01% for ≥ 2 years), demonstrate a favorable safety profile, and provide a good treatment value (cost versus efficacy and safety benefits).
    Keywords:  Cost-effectiveness; Generics; Imatinib; Price
    DOI:  https://doi.org/10.1016/j.clml.2025.10.001
  2. Hematology. 2025 Dec;30(1): 2569898
    Treatment of chronic myeloid leukemia chronic phase patients in third-line setting and beyond: recommendations from a Belgian expert panel in 2025.
    Peter Vandenberghe, Dominiek Mazure, Gaëlle Vertenoeil, Violaine Havelange, Adriano Salaroli.
       INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have revolutionized the therapy of chronic myeloid leukemia (CML) in chronic phase, opening up the perspective of a normal life expectancy for most patients and of treatment-free remission for some of them. However, intolerance or resistance may necessitate treatment modifications.
    METHODS: A panel of five Belgian experts reviewed the treatment options in Belgium in 2025 for patients with chronic phase CML with resistance or intolerance to at least two lines of therapy.
    DISCUSSION: In contrast to the early years of TKI therapy, several options are available as third-line therapy or beyond for CML patients resistant or intolerant to at least two prior TKIs. These include the third generation TKI ponatinib, the allosteric BCR::ABL1 inhibitor asciminib, allogeneic hematopoietic stem cell transplantation, continuation of ongoing second-line TKI therapy with or without dose modification, or switching to alternative second generation TKIs. Careful consideration of the potency and safety profiles of these options, the clinical context, and treatment goal is needed. Ponatinib is currently reimbursed in Belgium for patients with CML showing resistance or intolerance to at least two prior TKIs, or with the BCR::ABL1 T315I mutation, regardless of the number of previous TKIs. Asciminib is currently reimbursed for patients with resistance or intolerance to at least two prior TKIs, excluding those with the BCR::ABL1 T315I mutation. This review provides guidance to weigh available safety and efficacy data in a setting of resistance or intolerance to second-line therapy with the goal of selecting the best available personalized treatment.
    Keywords:  BCR::ABL1 mutation; chronic myeloid leukemia; chronic phase; intolerance; personalized medicine; resistance; third-line setting; tyrosine kinase inhibitors
    DOI:  https://doi.org/10.1080/16078454.2025.2569898
  3. Haematologica. 2025 Oct 30.
    Outcomes of patients with relapsed or refractory primary mediastinal B-cell lymphoma after frontline DA-EPOCH-R.
    Brian Hess, Alison Moskowitz, James A Davis, Paolo Strati, Yazeed Sawalha, Jonathan Bakos, Mckenzie Sorrell, Anna C Ferreira, Silvia Escribano-Serrat, Michelly De Castro, Taylor R Brooks, Brian T Hill, Gunjan L Shah, Ayo S Falade, Reid Merryman, Manali Kamdar, Andrew Ip, Victoria Nachar, Joseph G Bennett, Nicole Lux, Nausheen Ahmed, Marc Hoffmann, Ann LaCasce.
       INTRODUCTION: Most patients diagnosed with primary mediastinal B-cell lymphoma (PMBCL) achieve cure following standard of care therapy with frontline DA-EPOCH-R. However, treatment strategies following relapse after DA-EPOCH-R are not well defined.
    METHODS: We performed a retrospective review of PMBCL patients relapsed/refractory (R/R) after frontline DA-EPOCH-R to obtain better insight on outcomes with salvage therapy and autologous stem cell transplant (Auto-SCT).
    RESULTS: Our cohort consisted of 107 patients with R/R PMBCL. Ninety patients qualified for the intention to treat (ITT) salvage therapy (ST) analysis. With a median follow up of 48.9 months in the ST analysis, the median progression-free survival (PFS) was 5.4 months (95% CI: 2.3-not reached (NR)) with 5-year OS rate of 78% (95% CI: 69-88). Compared to relapsed patients (relapsing > 6 months after frontline DA-EPOCH-R, N=23), refractory patients (relapsing < 6 months after frontline DA-EPOCH-R, N=67) had inferior overall response rate (ORR) (48% vs 83%), complete remission (CR) rate (19% vs 44%), and 2-year PFS rate (30% vs 69%) with initial ST. Forty-eight patients (53%) underwent Auto-SCT after ST with estimated 5-year PFS and overall survival (OS) rates of 85% (95% CI: 75-96) and 88% (95% CI: 79-99), respectively. There were no relapses among 29 patients with CR prior to Auto-SCT.
    CONCLUSIONS: This analysis is the largest review of R/R PMBCL to date and demonstrates unfavorable outcomes for patients with refractory disease after frontline DA-EPOCH-R chemotherapy. Patients able to receive Auto-SCT, especially those with CR prior to Auto-SCT, had excellent outcomes.
    DOI:  https://doi.org/10.3324/haematol.2025.288232
  4. Leuk Res Rep. 2025 ;24 100549
    Pediatric chronic myeloid leukemia: A decade of clinical experience at the NBK specialized hospital for children.
    Maha Bourusly, Mohammad Adil Obaid, Nashwa Farag, Mona Bourhama, Sundos Alsharidah, Eman Almatar.
      Pediatric chronic myeloid leukemia is rare and differs from adult disease. We retrospectively reviewed 12 children (median age 8.4 years, six males) treated with imatinib (340 mg/m²/day) from 2010 to 2020; dasatinib was used for intolerance. All presented with leukocytosis (median WBC, 358 × 109/L) and splenomegaly. Imatinib achieved complete hematologic response in 92% by 3 months and 100% by 6 months; major molecular response was observed in all evaluable cases at 12 months. Three who lost response switched to dasatinib and maintained remission; two attained treatment-free remission. TKIs are effective; prospective studies should optimize risk stratification and discontinuation.
    Keywords:  Children; Chronic myeloid leukemia (CML); Imatinib; Retrospective study; Treatment outcomes; Tyrosine kinase inhibitors
    DOI:  https://doi.org/10.1016/j.lrr.2025.100549
  5. Cancers (Basel). 2025 Oct 17. pii: 3358. [Epub ahead of print]17(20):
    Bing-Neel Syndrome in Waldenström Macroglobulinemia: Updates on Clinical Management and BTK Inhibitor Efficacy.
    Masuho Saburi, Naohiro Sekiguchi.
      Bing-Neel syndrome (BNS), a rare complication of Waldenström macroglobulinemia (WM), is caused by the direct infiltration of lymphoplasmacytic cells into the central nervous system (CNS). Since clinical manifestations are heterogeneous and may overlap with IgM-related neuropathies, BNS is often under-recognized and diagnosed late. The incidence of BNS has been reported to be approximately 1% of patients with WM. Because of its extreme rarity, there are no prospective studies on BNS. In 2025, a consensus panel from the 12th international workshop on WM updated the guidelines for BNS, recognizing zanubrutinib as a standard therapy, clarifying imaging and cerebrospinal fluid (CSF) assessments during follow-up, and introducing revised response categories. Although the incidence of BNS is approximately 1% of WM, it decreases overall survival compared to WM alone, and early deaths were reported in historical series. Diagnostic confirmation requires a high index of suspicion and a multimodal approach combining MRI of the brain and spine with gadolinium, CSF cytology and flow cytometry, molecular testing such as MYD88 L265P, and occasionally tissue biopsy. Importantly, MYD88 L265P is also observed in most cases of diffuse large B-cell lymphoma of the CNS and is therefore not disease-specific. Differentiation from IgM-mediated neuropathies is critical because management strategies markedly differ. Historically, high-dose methotrexate- or cytarabine-based chemotherapy, intrathecal therapy, and radiotherapy have been used; however, responses varied, and toxicity was considerable. In contrast, CNS-penetrant Bruton tyrosine kinase (BTK) inhibitors have reshaped therapeutic strategies. Retrospective data support durable responses with ibrutinib, tirabrutinib, and zanubrutinib, while early findings suggest that non-covalent BTK inhibitors expand options for relapsed or refractory cases. Herein, we synthesize current evidence on epidemiology, pathophysiology, and diagnostic work-up. We also outline therapeutic recommendations integrating the genotype, disease pattern, and patient fitness and conclude with unmet needs and future directions.
    Keywords:  Bing–Neel syndrome; CXCR4; MRI; MYD88; Waldenström macroglobulinemia; cerebrospinal fluid; chemotherapy; ibrutinib; lymphoplasmacytic lymphoma; pirtobrutinib; radiotherapy; tirabrutinib; zanubrutinib
    DOI:  https://doi.org/10.3390/cancers17203358
  6. Blood. 2025 Oct 30. 146(18): 2153-2155
    ReXPOsing a weakness in TP53-mutant MDS and AML.
    Richard D'Andrea.
      
    DOI:  https://doi.org/10.1182/blood.2025030746
  7. Blood Neoplasia. 2025 Nov;2(4): 100165
    Final safety and efficacy results from a phase 1/2 study of tagraxofusp, a CD123-targeted therapy, for myelofibrosis.
    Abdulraheem Yacoub, Haris Ali, Vikas Gupta, Eunice S Wang, Mrinal M Patnaik, Gary J Schiller, Minakshi Taparia, Tariq I Mughal, Ross Lindsay, Antonio Galleu, Ira Gupta, Naveen Pemmaraju.
      Patients with myelofibrosis (MF) who are resistant to or relapse after Janus kinase inhibitor (JAKi) therapy have limited treatment options and typically poor prognoses. CD123 is overexpressed in various myeloid malignancies, including MF. Tagraxofusp is a first-in-class CD123-targeted therapy, and the only drug approved globally for the rare myeloid malignancy blastic plasmacytoid dendritic cell neoplasm. We conducted a phase 1/2 trial to determine optimal dosing, and evaluate safety and efficacy of tagraxofusp monotherapy in treatment-naïve (n = 5) MF and patients with MF resistant/refractory to JAKi (n = 25) and not eligible for stem cell transplant. There were no dose-limiting toxicities. The recommended phase 2 dose of tagraxofusp was 12 μg/kg per day for 3 consecutive days per cycle. In the safety population (n = 36) treated at 12 μg/kg per day, the most frequent grade ≥3 treatment-emergent adverse events were thrombocytopenia (19%), anemia (22%), and dyspnea (11%). Capillary leak syndrome occurred in 11% of patients, all during cycle 1 with resolution in all patients. Thirty patients treated at 12 μg/kg per day were efficacy evaluable. Of 18 (n = 2 treatment-naïve, n = 16 relapsed/refractory) patients with baseline splenomegaly, 2 relapsed/refractory patients had spleen volume reduction ≥35%. In relapsed/refractory patients, 40% had total symptom score (TSS) ≥50%, and median overall survival (OS) was 19.3 months. In patients who were treatment naïve, 40% had TSS ≥50%, and median OS was 26.6 months. In this trial, tagraxofusp monotherapy in MF was well tolerated, without cumulative myelotoxicity, and with symptom score improvements, warranting further investigation in combination therapy. This trial was registered at www.clincaltrials.gov as #NCT02268253.
    DOI:  https://doi.org/10.1016/j.bneo.2025.100165
  8. Int J Hematol. 2025 Oct 31.
    A retrospective analysis of clinicopathological and genetic features of synchronous CNS and systemic DLBCL at diagnosis.
    Kayo Egoshi Ohashi, Suguru Fukuhara, Akiko Miyagi Maeshima, Maki Shibata, Haruhi Makino, Daiki Hattori, Hirokazu Sasaki, Shinichi Makita, Noriko Iwaki, Wataru Munakata, Takahiro Fukuda, Miki Ando, Koji Izutsu.
      Synchronous central nervous system (CNS) and systemic diffuse large B-cell lymphoma (synDLBCL) is a rare, aggressive entity with poor prognosis and limited data guiding optimal management. We retrospectively analyzed 25 patients with synDLBCL treated at our institution between 2012 and 2021. Among the 20 patients undergoing curative-intent treatment, most received less-intensive CNS-directed therapies, including R-CHOP with intrathecal chemotherapy or high-dose methotrexate. The 3-year progression-free survival rate was 33%, with CNS progression as the predominant site of treatment failure. Genetic profiling in 12 patients revealed a high prevalence (83%) of the MCD subtype, characterized by frequent MYD88 and CD79B mutations, irrespective of immunohistochemical cell-of-origin classification. These findings align with the genetic landscape of primary CNS lymphoma, underscoring the limitations of less-intensive CNS-directed therapies in achieving durable CNS control in synDLBCL. Our findings highlight the need for CNS-penetrant, intensified frontline strategies and support the investigation of Bruton's tyrosine kinase inhibitor-containing regimens in this population. Multicenter collaborative studies with standardized diagnostic and treatment approaches are essential to improve outcomes in synDLBCL.
    Keywords:  Genetic profiling; Less-intensive CNS-directed therapy; MCD type; Secondary CNS lymphoma; Synchronous diffuse large B-cell lymphoma
    DOI:  https://doi.org/10.1007/s12185-025-04089-8
  9. Leukemia. 2025 Oct 27.
    ctDNA dynamics demonstrates rapid treatment response to tafasitamab + R-CHOP +/- lenalidomide and predicts outcome in diffuse large B-cell lymphoma: results from the phase 1b First-MIND study.
    EuroClonality-NGS Working Group
      The firstMIND trial (NCT04134936) evaluated the safety and efficacy of adding lenalidomide to R-CHOP+tafasitamab in the first-line treatment settings of patients with diffuse large B-cell lymphoma. To address response dynamics and the impact of measurable residual disease (MRD), we analyzed prospectively collected plasma samples from 56 study patients using the EuroClonality immunoglobulin gene (IG)-NGS assay. At baseline, disease-related clonotypes were identified in 50/56 (89%) patients by IG-NGS in cell-free (cf)DNA and/or FFPE samples. MRD markers were successfully identified in 49/52 (94%) cfDNA samples and 35/41 (85%) FFPE samples. Baseline cfDNA and circulating tumor (ct)DNA levels correlated with preclinical risk factors, and high cfDNA levels ≥3.35 log10hGE/ml plasma were significantly associated with poor progression-free survival (PFS) (hazard ratio (HR): 3.1). ctDNA clearance was rapid with 52% of patients MRD-negative at C2D1, 83% patients at C4D1, and 82% patients after finishing six 21-day cycles (end of treatment (EOT)) and a sustained treatment response (93% MRD negative) six months after EOT. ctDNA detection was associated with worse PFS outcomes at C2D1 (p = 0.039, HR:4.51, 95%Cl:0.93-21.74), C4D1 (p = 0.07, HR:3.34, 95%Cl:0.83-13.48) and EOT (p = 0.01, HR:6.38, 95%Cl:1.27-32.01) and inferior overall survival at these time points. In PET-positive patients, ctDNA-MRD had a higher specificity rendering PET/CT more precisely.
    DOI:  https://doi.org/10.1038/s41375-025-02759-4
  10. Intern Med. 2025 Oct 30.
    Effective Treatment with Ruxolitinib and Ropeginterferon Alfa-2b for Refractory TAFRO-like Syndrome.
    Satoko Oka, Yuina Ueda-Akagi, Takaya Mitsuyoshi, Kazuo Ono.
      Owing to the lack of appropriate treatment, TAFRO syndrome often presents with multiple organ dysfunction and fatality. The Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway has recently been shown to play an important role in the pathogenesis of inflammation in TAFRO syndrome, and inhibitors of the JAK/STAT pathway may be effective as therapeutic agents for TAFRO syndrome. We herein report the successful treatment using combination therapy with ruxolitinib and ropeginterferon alfa-2b of a case of TAFRO-like syndrome with a long history of polycythemia vera with JAK2 V617F refractory to several treatments.
    Keywords:  JAK/STAT pathway; TAFRO syndrome; ropegIFNα2b; ruxolitinib
    DOI:  https://doi.org/10.2169/internalmedicine.6348-25
  11. Blood Adv. 2025 Oct 30. pii: bloodadvances.2025017127. [Epub ahead of print]
    A Retrospective Study of Treatment and Outcomes in Synchronous Systemic and Central Nervous System Large B-cell Lymphoma.
    J Erika Haydu, Robert A Redd, Matthew M Lei, Ephraim Hochberg, Jeffrey A Barnes, Philippe Armand, Jacob D Soumerai, April Eichler, Eric D Jacobsen, Justin T Jordan, Caron A Jacobson, Ann S LaCasce, Isabel C Arrillaga-Romany, J R McFaline-Figueroa, Scott R Plotkin, Ronald W Takvorian, Ugonma Nnenna Chukwueke, Jennifer L Crombie, P Connor Johnson, Philipp Karschnia, Jörg Dietrich, Lakshmi Nayak, Jeremy S Abramson.
      Synchronous systemic and de novo secondary central nervous system (CNS) large B-cell lymphoma (LBCL) is an aggressive clinical entity with a historically poor prognosis. Given the rarity of this presentation, prospective studies are limited, and treatment paradigms and outcomes are extrapolated from small heterogenous retrospective studies. We performed a retrospective study with extended follow up for 63 consecutive patients with previously untreated synchronous systemic and de novo secondary CNS LBCLs presenting to two institutions over 21 years. Most patients had diffuse large B-cell lymphoma (73%) and were treated with an average of 6 cycles of R-CHOP intercalated with high dose intravenous methotrexate (R-CHOP-M). The overall response rate was 84% (75% complete). With a median follow up of 8.1 years, the median progression-free survival (PFS) was 1.2 years, and the 6-year PFS rate was 37%. The median overall survival (OS) was 7.9 years and the 6-year OS rate was 52%. Normal lactate dehydrogenase (LDH), low International Prognostic Index (IPI) score, and brain parenchymal-only CNS disease were associated with improved PFS, while LDH and parenchymal disease were associated with OS. The 25% of patients who underwent consolidation with high dose chemotherapy and autologous stem cell transplant (HDC/ASCT) had superior PFS and OS compared to non-transplanted patients, with particular benefit in IPI 3+. This study demonstrates that a proportion of patients presenting with secondary CNS involvement are cured with upfront chemoimmunotherapy with or without HDC/ASCT and helps identify prognostically favorable subgroups which can guide counseling of patients with this rare high-risk clinical presentation.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017127
  12. Blood Adv. 2025 Oct 30. pii: bloodadvances.2025017745. [Epub ahead of print]
    Decitabine-cedazuridine in patients with MDS and TP53 mutations.
    Samuel Urrutia, Koji Sasaki, Alex Bataller, Hagop M Kantarjian, Guillermo Montalban-Bravo, James McCloskey, Elizabeth A Griffiths, Karen W L Yee, Amer M Zeidan, Michael R Savona, Aram Oganesian, Yuri Sano, Harold Neal Keer, Guillermo Garcia-Manero.
      Patients with myelodysplastic syndromes (MDS) harboring TP53 mutations have poor outcomes. The objective of this study is to evaluate patients with TP53 mutations treated in the phase 2/3 studies of decitabine-cedazuridine (DEC-C) in MDS. We divided patients into three groups: TP53wt, TP53single-hit, and TP53multi-hit. We then performed propensity matching of patients who were treated with DEC-C vs a cohort of patients treated with parenteral hypomethylating agents (HMA). 180 patients were analyzed of which 73 (40.5%) had TP53 mutations, 23 (12%) with TP53multi-hit. Patients with TP53multi-hit more frequently had complex cytogenetics (69.5%), and had fewer median number of co-mutations (2.5, IQR 2-3) compared to TP53single-hit(3, IQR 1-5), or TP53wt (4, IQR 3-6) (p=0.002). Patients with TP53multi-hit had a higher chance of lack of response with 39.1% vs 28.1% for TP53single-hit (p=0.2). Patients with TP53mult-hit lost response earlier at 8.2 months, vs 13.2 months for TP53single-hit, and 15.1 months for TP53wt (p=0.1). Median overall survival (mOS) was 11.5 months (95% CI: 8.6 - 19.1) for TP53mult-hit, 22.1 months (95% CI: 14.6 - 35.9) for TP53single-hit, and 31.7 months (95% CI: 19.5 - 51.1) for TP53wt (log-rank, p < 0.005). Propensity scores matched 47 TP53mutpatients treated with DEC-C and 47 TP53mut patients treated with single agent parenteral HMA. Median survival was 13.1 months (95% CI: 8.4 - 21.3) for DEC-C vs 8.0 months (95% CI: 5.2 - 13.0) for single agent parenteral HMA (log-rank, p=0.047). In patients with MDS harboring TP53mut, DEC-C may improve overall survival compared to parenteral HMA.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017745
  13. Blood Adv. 2025 Oct 30. pii: bloodadvances.2025017620. [Epub ahead of print]
    Retreatment with R-CHOP-like Therapy in Patients with Late Relapse of Diffuse Large B-Cell Lymphoma.
    Jean-Nicolas Champagne, Diego Villa, Alina S Gerrie, Christopher P Venner, Graham W Slack, Pedro Farinha, Jeffrey W Craig, Laura K Hilton, Kerry J Savage, David W Scott, Laurie H Sehn.
      Patients with diffuse large B-cell lymphoma (DLBCL) with late relapse (>2 years from diagnosis) may be treated with a second course of R-CHOP-like therapy particularly if comorbidities preclude more intensive options. Patients with de novo DLBCL initially treated with an R-CHOP-like regimen who developed late relapse and were retreated with curative-intent R-CHOP-like therapy were identified through BC Cancer databases. Sixty-five patients were identified; at relapse: median age 77 years (range, 52-89), 81% stage III-IV, 52% ECOG performance status 2-4, 78% IPI score 3-5. Median time from original diagnosis was 7.4 years (range, 2.5-15.9). Median number of cycles of R-CHOP-like therapy received at relapse was 5 (range 1-6). Overall response rate was 72%; 57% complete response. With a median follow-up of 31 months, 2-year time-to-progression (TTP) was 54%, 2-year progression-free survival was 46%, 2-year disease-specific survival was 64% and 2-year overall survival was 54%. Patients relapsing >5 years from diagnosis had better TTP, with a 2-year TTP of 66% compared to 9% for patients relapsing between 2-5 years (HR 0.30 [95%CI 0.14-0.64]; p=0.001). Many patients with late-relapsing DLBCL may be effectively treated with further R-CHOP-like therapy, avoiding more intensive and costly secondary therapies.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017620
  14. Leuk Lymphoma. 2025 Oct 31. 1-4
    Nivolumab with doxorubicin, vinblastine, and dacarbazine for the frontline treatment of central nervous system classical Hodgkin lymphoma.
    Mollie Reese, Jess Hatfield, Carlos Zamora, Christopher Dittus.
      
    DOI:  https://doi.org/10.1080/10428194.2025.2577256
  15. Int J Mol Sci. 2025 Oct 20. pii: 10207. [Epub ahead of print]26(20):
    Using a Novel Consensus-Based Chemoinformatics Approach to Predict ADMET Properties and Druglikeness of Tyrosine Kinase Inhibitors.
    Evangelos Mavridis, Dimitra Hadjipavlou-Litina.
      The urgent need to reduce the cost of new drug discovery has led us to create a new, more selective screening method using free chemoinformatics tools to restrict the high failure rates of lead compounds (>90%) during the development process because of the lack of clinical efficacy (40-50%), unmanageable toxicity (30%), and poor drug-like properties (10-15%). Our efforts focused on new molecular entities (NMEs) with reported activity as tyrosine kinase inhibitors (small molecules) as a class of great potential. The criteria for the new method are acceptable Druglikeness, desirable ADME (absorption, distribution, metabolism, and excretion), and low toxicity. After a bibliographic review, we first selected the 29 most promising compounds, always according to the literature, then collected the in silico calculated data from different platforms, and finally processed them together to conclude at 14 compounds meeting the aforementioned criteria. The novelty of the present screening method is that for the evaluation of the compounds for Druglikeness, and ADMET properties (absorption, distribution, metabolism, excretion, and toxicity), the data of the different platforms were used as a whole, rather than the results of each platform individually. Additionally, we validated our new consensus-based method by comparing the final in silico results with the experimental values of FDA (Food and Drug Administration)-approved tyrosine kinase drugs. Using inferential statistics of 39 FDA-approved tyrosine kinase drugs obtained after applying our method, we delineated the intervals of the desired values of the physicochemical properties of future active compounds. Finally, molecular docking studies enhance the credibility of the applied method as an identification tool of Druglikeness.
    Keywords:  ADMET properties; druglikeness; method validation; molecular docking; tyrosine kinase inhibitors
    DOI:  https://doi.org/10.3390/ijms262010207
  16. Blood. 2025 Oct 30. 146(18): 2148-2150
    Bispecific antibodies in action: the reality of engagement.
    Mazyar Shadman, Ajay K Gopal.
      
    DOI:  https://doi.org/10.1182/blood.2025030376
  17. Hematology. 2025 Dec;30(1): 2565956
    NPM1 mediated up - regulation of CXCR4 might drive bortezomib resistance in multiple Myeloma.
    Yuye Shi, Yuan Deng, Jingjing Ma, Yunjie Li, Tingting Ji, Hong Tao, Chunling Wang, Liang Yu.
       OBJECTIVE: Bortezomib (BTZ) containing regimens induces significant antitumor response in multiple myeloma (MM) and are considered as the first-line treatment. However, resistance is still one of the unsolved problems. This study aims to explore the mechanism underlying BTZ resistance in MM.
    METHODS: The gene expression profile (GEP) data of the GEO dataset GSE9782 was analyzed. All cases were divided into BTZ sensitive and resistant arms. Differentially expressed genes (DEGs) and later the hub genes between the two groups were screened. The key hub gene NPM1 was inhibited by shRNA and small molecule inhibitor, proliferation, apoptosis and expression of CXCR4 in myeloma cells were assayed.
    RESULTS: NPM1 was a dismal survival prognostic factor in MM, and MM patients with high NPM1 expression achieved significantly lower response rate to BTZ-containing regimens. In vitro, qRT-PCR revealed that NPM1 expression in the BTZ-resistant MM cell line KM3/BTZ (also known as KB) was significantly higher than its parental cell line KM3 cells. Knockdown of NPM1 and treatment with the NPM1 inhibitor NSC348884 both restored the sensitivity of KB cells to BTZ. Further analysis revealed that inhibition of NPM1 down-regulated CXCR4 expression at both transcriptional and translational level.
    CONCLUSION: In conclusion, NPM1 might causes BTZ resistance via up-regulating CXCR4 expression in MM and could be served as both a new prognostic biomarker and a promising therapeutic target.
    Keywords:  Bortezomib resistance; Chemokine C-X-C-motif receptor 4; Multiple myeloma; Nucleophosphorin 1
    DOI:  https://doi.org/10.1080/16078454.2025.2565956
  18. Cancers (Basel). 2025 Oct 18. pii: 3372. [Epub ahead of print]17(20):
    Novel Molecular Insights and Evolution of Less Toxic Therapeutic Strategies in Burkitt Lymphoma.
    Coen J Lap, Kieron Dunleavy.
      Burkitt lymphoma (BL) is a rare, aggressive B-cell lymphoma that is characterized by rapid tumor proliferation and frequent extra-nodal involvement. While prompt diagnosis and initiation of highly intensive chemotherapy results in cure rates over 90% in children and adolescents, outcomes in adults are more modest, as comorbidities and advancing age may compromise treatment tolerability. In recent years, intermediate-intensity regimens have been developed for BL. These are highly effective in patients of all ages and associated with significantly less treatment-related toxicity compared to traditional high-dose chemotherapy. This was demonstrated in a recent randomized study of dose-intensive R-CODOX-M/R-IVAC compared to the reduced-intensity DA-EPOCH-R regimen, which was associated with equivalent outcomes but with significantly fewer side effects. Regardless of the chemotherapy platform, CNS involvement at baseline predicts a significantly inferior outcome, and the development of an optimal approach for these patients is an area of unmet need in BL therapeutics. Patients with relapsed or refractory disease following frontline therapy have very short survival times, as currently available salvage options are largely ineffective. In this regard, novel agents such as anti-CD19 CAR-T cells and bi-specific antibodies are under development in BL. It is hoped that progress in novel drug development, alongside improved understanding of BL biology, to further elucidate its genetic and epigenetic vulnerabilities, will lead to improved outcomes for patients in the future.
    Keywords:  BL; EBV; MYC; reduced-intensity regimen; relapsed disease; risk-adapted approach
    DOI:  https://doi.org/10.3390/cancers17203372
  19. Res Pract Thromb Haemost. 2025 Oct;9(7): 103191
    Andexanet alfa for the reversal of the low-molecular-weight heparin enoxaparin.
    Thijs F van Haaps, Alexander P Benz, Lizhen Xu, Saskia Middeldorp, John W Eikelboom, Truman J Milling, Mark Crowther, Lisa Holer, Stephan Nolan, Per Ladenvall, Genmin Lu, Michiel Coppens.
       Background: Andexanet alfa (andexanet) is the only approved reversal agent for patients with acute major bleeding during apixaban or rivaroxaban treatment. Its mechanism suggests it may also reverse the effects of low-molecular-weight heparin.
    Aim: To evaluate the effects of andexanet in healthy volunteers and in patients with acute major bleeding on enoxaparin.
    Methods: In the first study, healthy volunteers received enoxaparin 1 mg/kg twice daily for ≥3 doses and were randomized to receive either andexanet or placebo in high- or low-dose regimens, given 3 hours (high dose) or 8 hours (low dose) after the last dose. In the second study (Andexanet Alfa, a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors 4), dosing depended on timing and amount of last enoxaparin dose: high dose if > 40 mg or <8 hours since last dose (or unknown), low dose if ≤ 40 mg or ≥8 hours. The high dose consisted of an 800 mg bolus followed by 960 mg >2 hours, while low dose consisted of a 400 mg bolus followed by 480 mg >2 hours. The primary outcome was change in anti-Xa activity. Hemostatic efficacy was assessed in patients with confirmed bleeding and baseline anti-Xa ≥ 0.25 IU/mL.
    Results: In the first study, 24 volunteers received andexanet (12 at a high dose and 12 at a low dose), and 7 received a placebo. Median anti-Xa activity decreased by 83% (0.92-0.17 IU/mL) in the high-dose cohort, and by 73% (0.78-0.22 IU/mL) in the low-dose cohort. In the second study, 22 patients received andexanet; anti-Xa activity decreased by 75% (95% CI, 67%-79%; 0.48-0.14 IU/mL). Good/excellent hemostasis was achieved in 14 of 16 assessable patients (88%).
    Conclusion: In enoxaparin-treated subjects, andexanet reduced anti-Xa activity and achieved effective hemostasis in 88% of patients. Results align with findings of patients using apixaban, rivaroxaban, or edoxaban.
    Keywords:  andexanetalfa; enoxaparin; hemorrhage; heparin, low-molecular-weight; intracranial hemorrhages; venous thromboembolism
    DOI:  https://doi.org/10.1016/j.rpth.2025.103191
  20. Blood. 2025 Oct 29. pii: blood.2025031086. [Epub ahead of print]
    High-grade/large B-cell lymphoma-11q has a very good prognosis in children and young people without a predisposition.
    Leila Ronceray, Minke Henrina Willemina Huibers, Katrin Reutter, Oussama Abla, Mara Andres, Olga Balagué, Monika Csoka, Gil Gilad, Melanie M Hagleitner, Daiki Hori, Lisa Lyngsie Hjalgrim, Janez Jazbec, Wolfram Klapper, Atsuko Nakazawa, Jaime Verdu-Amorós, Hannah von Mersi, Wilhelm Woessmann, Ana C Xavier, Birgit Burkhardt, Itziar Salaverria, Andishe Attarbaschi.
      High-grade B-cell lymphoma with 11q-aberration (HGBCL-11q) is a rare pediatric non-Hodgkin lymphoma. This study assessed outcome in 90 children with HGBCL-11q. With survival rates ≥95%, patients with HGBCL-11q and no predisposition are candidates for deescalated therapy in future prospective trials.
    DOI:  https://doi.org/10.1182/blood.2025031086
  21. Oncology (Williston Park). 2025 Oct 21. 39(9): 424-430
    Progress in the Treatment of Advanced-Stage Classical Hodgkin Lymphoma in the PET-Adapted Era.
    Wael Abdulla Moh Khair Md.
      Interim fluorodeoxyglucose (FDG)-PET is currently the most used predictor of early response to treatment in advanced-stage Hodgkin lymphoma. Patients with a negative PET after 2 cycles of chemotherapy (PET2) have a better treatment outcome than their counterparts. The objective of this review was to assess how PET-adapted treatment approaches have enhanced the management of advanced-stage Hodgkin lymphoma by adapting treatment according to initial response. PubMed, Web of Science, ScienceDirect, Google Scholar, Scopus, and the Cochrane Library were systematically searched using randomized controlled trials, phase 2/3 clinical trials, and systematic reviews between 2000 and 2024. Keywords used were "Hodgkin lymphoma," "PET-adapted treatment," "ABVD," "BEACOPP," "interim PET," and "treatment escalation/de-escalation." PET-adapted treatment strategies decrease PET2-negative patient treatment, decreasing adverse effects with no reduction in effectiveness, as evidenced by the RATHL, AHL2011, and HD18 trials. In PET2-positive patients, trials such as SWOG S0816 and HD0607 prove that the early intensification of treatment improves survival. Novel treatments, such as brentuximab vedotin and nivolumab, are promising options.
    DOI:  https://doi.org/10.46883/2025.25921053
  22. Blood Adv. 2025 Oct 31. pii: bloodadvances.2025017938. [Epub ahead of print]
    Long-term Efficacy and Safety of Ropeginterferon Alfa-2b under its HIDAT Regimen for the Treatment of Polycythemia Vera.
    Shanshan Suo, Rongfeng Feng Fu, Albert Qin, Zonghong Shao, Jie Bai, Hu Zhou, Na Xu, Suning Chen, Xuelan Zuo, Xin Du, Minghui Duan, Li Wang, Pei Li, Xuhan Zhang, Sujiang Zhang, Daoxiang Wu, Jingjing Zhang, Zhijian Xiao, Lei Zhang, Jie Jin.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2025017938
  23. Future Oncol. 2025 Oct 31. 1-13
    Plain language summary about tirabrutinib in relapsed/refractory primary central nervous system lymphoma.
    Kazuhiko Sugiyama, Yoshitaka Narita, Motoo Nagane, Kazuhiko Mishima, Yasuhito Terui, Yoshiki Arakawa, Katsunori Asai, Noriko Fukuhara, Hajime Yonezawa, Naoki Shinojima, Arata Aoi, Ryo Nishikawa.
      
    Keywords:  BTKi; Bruton’s tyrosine kinase inhibitor; ONO-4059; PCNSL; primary central nervous system lymphoma; tirabrutinib
    DOI:  https://doi.org/10.1080/14796694.2025.2574838
  24. Blood Cancer J. 2025 Oct 27. 15(1): 184
    Granulocyte colony-stimulating factor plus venetoclax and azacitidine in newly diagnosed acute myeloid leukemia: a multicenter phase 2 trial.
    Huaiyu Wang, Xiaohui Wang, Ting Shi, Suhua Wei, Xin Li, Yun Leng, Yin Wu, Mei Sun, Pengcheng He, Hong-Hu Zhu.
      
    DOI:  https://doi.org/10.1038/s41408-025-01389-4
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