bims-hemali Biomed News
on Hematologic malignancies
Issue of 2025–05–25
thirteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Efficacy and safety of the R2-MTX regimen in primary central nervous system lymphoma (PCNSL): a single-center retrospective analysis.
  2. Blitzing ALL with blinatumomab.
  3. Dasatinib-related diffuse alveolar hemorrhage in de novo blast phase chronic myeloid leukemia: a case report.
  4. Ropeginterferon-α2b discontinuation after long-term exposure: four cases from a single institution.
  5. Carfilzomib in combination with R-CHOP for initial treatment of patients with non-germinal center diffuse large B-cell lymphoma: a multicenter, single arm, phase 1/2 study.
  6. Treatment-free remission in chronic myeloid leukemia with rare ABL1 gene fusions: Real-life study from the French CML group Fi-LMC.
  7. Immunotherapy response: is it all in the DLBCL-IQs?
  8. N-acetyl-L-cysteine promoted hematopoietic recovery in patients with acute myeloid leukemia after complete remission--A pilot study.
  9. Efficacy and Safety of the Bruton's Tyrosine Kinase Inhibitor Zanubrutinib in Immune Thrombocytopenia.
  10. The biology of chronic myeloid leukemia: an overview of the new insights and biomarkers.
  11. Ultrasensitive detection of circulating multiple myeloma cells by next-generation flow after immunomagnetic enrichment.
  12. Daratumumab monotherapy as a desensitization strategy prior to cardiac transplantation.
  13. Next generation Bruton's tyrosine kinase inhibitors - characterization of in vitro potency and selectivity.
  1. J Cancer Res Clin Oncol. 2025 May 22. 151(5): 173
    Efficacy and safety of the R2-MTX regimen in primary central nervous system lymphoma (PCNSL): a single-center retrospective analysis.
    Lijie Liang, Xue Meng, Li Xie, Na Li, You Feng, Ming Jiang.
       PURPOSE: Primary central nervous system lymphoma (PCNSL) has a poor prognosis, mainly because of the significant challenges with the efficacy and tolerability of induction chemotherapy. This retrospective study aimed to evaluate the efficacy and safety of the R2-MTX regimen in PCNSL patients.
    METHODS: We conducted a retrospective analysis of 39 PCNSL patients treated with the R2-MTX regimen, focusing on treatment outcomes and adverse events (AEs).
    RESULTS: The overall response rate (ORR) was 72.2%, with a complete response (CR) rate of 69.4% and a partial response (PR) rate of 2.8%. With a median follow-up of 37.2 months (interquartile range [IQR] 24.2-47.5), the estimated 2-year progression-free survival (PFS) and overall survival (OS) rates were 54.9% (95% CI, 37.2-69.5%) and 78.5% (95% CI, 59.8-89.2%), respectively. The most common grade 3 or 4 AEs included neutropenia (33.3%), leukopenia (13.9%), anemia (2.8%), and thrombocytopenia (2.8%). Consolidation or maintenance therapy was associated with prolonged survival in PCNSL patients (2-year OS rates 100% vs. 42.9%, P = 0.067). Survival analysis revealed that clinicopathological factors, such as double-expressor lymphoma (DEL), ECOG PS ≥ 2, and high-risk classification based on the Memorial Sloan Kettering Cancer Center model (MSKCC), predicted poor survival.
    CONCLUSIONS: Our results underscore the therapeutic potential of the R2-MTX regimen in managing newly diagnosed PCNSL patients. Further prospective studies with larger patient cohorts are imperative to solidify these preliminary findings.
    Keywords:  Clinicopathological factors; Consolidation therapy; Maintenance therapy; Primary central nervous system lymphoma (PCNSL); R2-MTX regimen
    DOI:  https://doi.org/10.1007/s00432-025-06205-x
  2. Blood. 2025 May 22. 145(21): 2400-2402
    Blitzing ALL with blinatumomab.
    Mark R Litzow.
      
    DOI:  https://doi.org/10.1182/blood.2025028576
  3. Fukushima J Med Sci. 2025 May 17.
    Dasatinib-related diffuse alveolar hemorrhage in de novo blast phase chronic myeloid leukemia: a case report.
    Kengo Suzuki, Daisuke Koyama, Yasuhito Suzuki, Kiyohito Hayashi, Yasuhiro Uchida, Yuki Sato, Koichiro Fukuchi, Masahiko Fukatsu, Yoko Shibata, Takayuki Ikezoe.
      Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL tyrosine kinase. Tyrosine kinase inhibitors (TKIs) have significantly improved the outcome of CML patients. Dasatinib, a second-generation TKI, is highly effective but associated with off-target effects, including pulmonary toxicities. While pleural effusion induced by dasatinib has been linked to therapeutic efficacy, its role remains controversial. Severe pulmonary complications, such as diffuse alveolar hemorrhage (DAH), can lead to treatment failure and increased mortality. We report a 72-year-old man with de novo blast-phase CML on clopidogrel who developed respiratory failure due to DAH 16 days after initiating dasatinib and prednisolone as induction therapy. Immediate steroid pulse therapy with methylprednisolone (1,000 mg/day for three days) was administered, and both dasatinib and clopidogrel were discontinued. Maintenance prednisolone (1 mg/kg/day) was then tapered by 10 mg per week. The patient's symptoms and radiographic findings improved without recurrence during tapering. This case highlights the importance of early recognition and management of severe complications like DAH in patients receiving dasatinib. Careful monitoring is essential to mitigate the risk of life-threatening respiratory failure and optimize CML treatment outcomes.
    Keywords:  chronic myeloid leukemia; dasatinib; diffuse alveolar hemorrhage
    DOI:  https://doi.org/10.5387/fms.25-00003
  4. Int J Hematol. 2025 May 21.
    Ropeginterferon-α2b discontinuation after long-term exposure: four cases from a single institution.
    Shuichi Shirane, Tadaaki Inano, Yasutaka Fukuda, Tomonori Ochiai, Naoko Midorigawa, Soji Morishita, Miki Ando, Norio Komatsu.
      Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm driven by JAK2 mutations, leading to the overproduction of blood cells. Ropeginterferon-α-2b (RopegIFN) has emerged as a promising therapy, capable of lowering the JAK2V617F allele burden and maintaining a complete hematologic response (CHR). Here, we report the cases of four patients with PV who discontinued RopegIFN after achieving CHR. One patient had sustained long-term remission post-discontinuation, with the JAK2V617F allele burden reduced below 10%, and met the criteria for an "operational cure." However, the other three patients experienced rising blood counts, resulting in loss of CHR. These findings underscore the importance of a robust molecular response in predicting sustainable remission. Continuous therapy remains the standard approach due to the lack of predictive models to identify patients who can safely discontinue RopegIFN. In the future, it will be necessary to verify whether patients who have achieved an "operational cure" can remain treatment free.
    Keywords:   JAK2 V617 F; Operational cure; Polycythemia vera; Ropeginterferon-α2b
    DOI:  https://doi.org/10.1007/s12185-025-04008-x
  5. Leuk Lymphoma. 2025 May 21. 1-10
    Carfilzomib in combination with R-CHOP for initial treatment of patients with non-germinal center diffuse large B-cell lymphoma: a multicenter, single arm, phase 1/2 study.
    Brian T Hill, Pallawi Torka, Francisco Hernandez-Ilizaliturri, Robert Dean, Deepa Jagadeesh, Kasra Karamlou, Chieh-Lin Fu, Allison M Winter, Wesam Ahmed, Mitchell Smith, Alex Mejia Garcia, Brenda Cooper, Ethan Krauspe, Jonathan Zhou, Taylor Brooks, Merve Kacar, Jenna Thomas, Hong Li, Xuefei Sophie Jia, Yanwen Chen, Paolo Caimi.
      We performed a phase I/II trial to explore the safety and efficacy of carfilzomib (K) in combination with R-CHOP (KR-CHOP) in patients with diffuse large B cell lymphoma (DLBCL). A total of 48 patients were enrolled and 47 were treated. The overall response rate (ORR) was 89% (70% complete response). At a median follow-up of 31 months, 3-year Kaplan-Meier estimates of PFS and OS were 79% and 87%, respectively. Treatment with KR-CHOP for non-GC DLBCL was associated with a decreased risk of disease progression and death relative to standard of care treatment with R-CHOP with hazard ratios (HR) of 0.16 [95% confidence interval (CI) 0.04-0.58, p = 0.002] and 0.31 [(95% CI, 0.09 - 0.99), p = 0.02], respectively. The most common grade 3 or 4 adverse events (AEs) were anemia (13%), thrombocytopenia (9%) and febrile neutropenia (9%). KR-CHOP is safe and may have preferential activity in non-GC DLBCL.
    Keywords:  ABC (non-GC) Subtype; Diffuse Large B-Cell Lymphoma; Proteosome Inhibitor
    DOI:  https://doi.org/10.1080/10428194.2025.2504156
  6. Leuk Res. 2025 May 14. pii: S0145-2126(25)00076-1. [Epub ahead of print]154 107716
    Treatment-free remission in chronic myeloid leukemia with rare ABL1 gene fusions: Real-life study from the French CML group Fi-LMC.
    Hyacinthe Johnson-Ansah, Aude Charbonnier, Gabriel Etienne, Lydia Roy, Laurence Legros, Gabrielle Roth-Guépin, Corentin Orvain, Anne Bouvier, Emilie Cayssials, Valérie Coiteux, Philippe Rousselot, Dina Naguib, Gandhi Damaj, Delphine Lebon, François-Xavier Mahon, Pascale Flandrin-Gresta, Stéphanie Dulucq, Sandrine Hayette, Jean-Michel Cayuela, Franck-Emmanuel Nicolini, Delphine Rea.
      Tyrosine kinase inhibitors of the BCR::ABL1 oncoprotein can be stopped without subsequent molecular relapse or major safety concerns in 40-80 % of adult patients with P210BCR::ABL1 positive chronic myeloid leukemia with sustained deep molecular responses. In contrast, ending treatment in patients with rare rearrangements located outside the major BCR region or within the exon 3 of ABL1 remains to be explored. Twenty-four patients with chronic phase disease and diverse uncommon BCR::ABL1 transcripts who obtained sustained molecular residual disease negativity and stopped therapy in a real-life setting for various reasons were retrospectively evaluated for treatment-free remission determinants. Six patients relapsed after a median time of 6 months (range; 3-49), relapse being defined as a rise in molecular residual disease above the 3-log threshold. Treatment-free remission probabilities at 12 and 60 months were 83.3 % (95 % CI: 68.4-98.2 %) and 70.6 % (95 % CI: 49.5-91.6), respectively. The type of BCR::ABL1 transcript was the only relevant baseline factor associated with durable treatment-free remission and patients with fusions lacking exon a2 sequences had the best outcome. To conclude, treatment-free remission is a reasonably achievable goal in patients with rare ABL1 fusion transcripts. Our results pave the way for recommendations in clinical practice. Nevertheless, further research is needed to determine which patients have highest chances to reach deep molecular response levels and become free from therapy and to decipher the biological impact of the different molecular rearrangements of BCR::ABL1 on treatment-free remission.
    Keywords:  Chronic myeloid leukemia – rare transcripts – tyrosine kinase inhibitor- treatment-free remission
    DOI:  https://doi.org/10.1016/j.leukres.2025.107716
  7. Blood. 2025 May 22. 145(21): 2402-2403
    Immunotherapy response: is it all in the DLBCL-IQs?
    Jessica Okosun.
      
    DOI:  https://doi.org/10.1182/blood.2025028443
  8. Cancer Lett. 2025 May 20. pii: S0304-3835(25)00379-9. [Epub ahead of print] 217812
    N-acetyl-L-cysteine promoted hematopoietic recovery in patients with acute myeloid leukemia after complete remission--A pilot study.
    Li-Juan Hu, Chen-Yuan Li, Tong Xing, Yu Wang, Qian Jiang, Hao Jiang, Jing Wang, Fei-Fei Tang, Ying-Jun Chang, Xiao-Hui Zhang, Yuan Kong, Xiao-Jun Huang.
      Chemotherapy is a cornerstone treatment for acute leukemia (AL), but it often results in bone marrow (BM) failure, leading to infections, anemia, and bleeding, which significantly impact patient survival. Endothelial progenitor cells (EPCs) are critical elements of the BM microenvironment and are essential for hematopoiesis. Our previous research using in vitro and AML mouse models indicated that BM EPC dysfunction, characterized by impaired angiogenesis and elevated reactive oxygen species (ROS) levels in AML patients, could be partially reversed after complete remission (CR) and further improved with N-acetyl-L-cysteine (NAC) treatment. This pilot cohort study (NCT06024031, www.clinicaltrials.gov) evaluated the effects of NAC on hematopoietic recovery in 30 newly diagnosed AML patients after induction chemotherapy, compared to a propensity-matched control group of 60 patients. Patients received oral NAC (400 mg, three times daily) for 28 days post-chemotherapy alongside standard supportive care. NAC treatment did not affect CR rates (90% vs. 80%, P=0.23), but significantly shortened platelet recovery time (19 vs. 22 days, P=0.0001) among CR patients. NAC improved EPC percentages, reduced ROS, and enhanced EPC hematopoiesis-supporting functions in patients who achieved CR. NAC was safe and effective in promoting normal hematopoiesis recovery in AML patients in CR following chemotherapy.
    Keywords:  Acute myeloid leukemia; Complete remission; Hematopoiesis; N-acetyl-L-cysteine
    DOI:  https://doi.org/10.1016/j.canlet.2025.217812
  9. Am J Hematol. 2025 May 20.
    Efficacy and Safety of the Bruton's Tyrosine Kinase Inhibitor Zanubrutinib in Immune Thrombocytopenia.
    Qiu-Sha Huang, Hai-Xia Fu, Chen-Cong Wang, Xiao-Lu Zhu, Yun He, Jin Wu, Qi Chen, Peng Zhao, Zhuo-Yu An, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang.
      Immune thrombocytopenia (ITP) is characterized by impaired platelet production and increased platelet destruction. Zanubrutinib is a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor that may reduce autoantibody production and reduce macrophage Fcγ receptor-mediated platelet destruction. In this single-arm, phase II study, we aimed to assess the efficacy and safety of zanubrutinib in corticosteroid-resistant or relapsed ITP. All patients received 80 mg zanubrutinib once daily for 6 weeks followed by a 20-week safety follow-up period. The primary endpoint was overall response (OR), defined as at least two consecutive platelet counts of at least 30 × 109/L, at least a 2-fold increase in the baseline count, the absence of bleeding, and no need for rescue therapy at 4 weeks. The trial was registered with ClinicalTrials.gov, number NCT05279872. Between January 1, 2022 and October 30, 2022, 20 patients were enrolled. The median platelet count was 19 (10-25) × 109/L at the time of enrollment. Participants had received a median of 4 (3-6) different therapies for ITP. Eleven (55%, 95% CI: 31.5%-76.9%) patients achieved an OR to the intervention. Two (10%) patients achieved a complete response. At the 6-month follow-up, a sustained response was achieved in seven (35.0%, 95% CI: 15.4%-59.2%) patients. There were no grade 4 or worse adverse events or treatment-related deaths. The most common adverse events were upper respiratory tract infection (in 25% of the patients). Zanubrutinib showed an encouraging response rate and tolerability, supporting its therapeutic potential for the treatment of ITP. Trial Registration: ClinicalTrials.gov identifier: NCT05279872.
    Keywords:  Bruton's tyrosine kinase inhibitor; clinical trials; immune thrombocytopenia
    DOI:  https://doi.org/10.1002/ajh.27718
  10. Front Oncol. 2025 ;15 1546813
    The biology of chronic myeloid leukemia: an overview of the new insights and biomarkers.
    Anna Sicuranza, Alessia Cavalleri, Simona Bernardi.
      Chronic myeloid leukemia is one of the onco-hematologic diseases in which the identification of disease markers and therapeutic advances have been particularly impactful. Despite this, significant gaps remain in our understanding of disease pathogenesis, progression, mechanisms of immune escape, and resistance to standard therapies. Recently, advances in technology and biological knowledge have drawn attention to several promising areas of research. Among these, leukemic stem cells, miRNAs, extracellular vesicles, and additional BCR::ABL1 mutations, with particular reference to the ASXL1 gene, have been the most extensively investigated. In this review we summarized and critically commented the main findings on these key topics over the past 5 years, evaluating their potential impact on patient management and their role in the development of new therapeutic strategies.
    Keywords:  ASXL1; BCR::ABL1; CD26; CML; EVs; biological markers; leukemic stem cell; miRNA
    DOI:  https://doi.org/10.3389/fonc.2025.1546813
  11. Blood. 2025 May 22. pii: blood.2025029234. [Epub ahead of print]
    Ultrasensitive detection of circulating multiple myeloma cells by next-generation flow after immunomagnetic enrichment.
    Marta Lasa, Carmen Gonzalez, Laura Notarfranchi, Anastasiia Zherniakova, Diego Alignani, Leire Burgos, Maria José Calasanz, Paula Rodriguez-Otero, Jose J Perez, Clara Gomez, Veronica Gonzalez-Calle, Felipe de Arriba, Luis Palomera Bernal, Miguel Angel Alvarez Rivas, Esther Clavero Sanchez, Enrique M Ocio, Ana Pilar Gonzalez-Rodriguez, Sunil Lakhwani, Angela Ibañez, Albert Oriol, Anna Sureda, Laura Rosiñol, Christiane Siewert, Alberto Orfao, Juan-Jose Lahuerta, Joan Bladé, Maria-Victoria Mateos, Jesús F San-Miguel, Maria-Teresa Cedena, Joaquin Martinez-Lopez, Noemi Puig, Bruno Paiva.
      The continuous improvement in progression-free survival (PFS) of multiple myeloma (MM) patients raises interest in evaluating peripheral residual disease (PRD) towards more frequent readouts of tumor kinetics while preserving quality of life. Here we present BloodFlow, a new method that combines immunomagnetic enrichment of CD138+ circulating plasma cells in peripheral blood (PB) with next-generation flow (NGF), for the detection of PRD below the 2x10-6 NGF threshold. BloodFlow detected PRD in 55/644 (8.5%) PB samples collected from 295 MM patients. Of note, 29/55 (52.7%) PB samples were positive using BloodFlow and negative by NGF. The lowest level of PRD detected by BloodFlow was 6x10-8. Considering patients' minimal residual disease (MRD) status in bone marrow as the reference, BloodFlow showed positive and negative predictive values of 95.1% and 76.6%. Presence of PRD during maintenance or observation predicted dismal progression-free and overall survival (2-year rates of 0% and 62%). BloodFlow surpassed NGF in PB and retained independent prognostic value for PFS in multivariate analysis including transplant-eligibility, the Revised International Staging System, complete remission and MRD status in bone marrow. BloodFlow is the first flow cytometry method that detects tumor cells below the 10-6 threshold, which resulted in improved minimally-invasive monitoring of MM patients.
    DOI:  https://doi.org/10.1182/blood.2025029234
  12. J Heart Lung Transplant. 2025 May 16. pii: S1053-2498(25)00063-4. [Epub ahead of print]
    Daratumumab monotherapy as a desensitization strategy prior to cardiac transplantation.
    Ruben J Crespo-Diaz, Adrian J daSilva-deAbreu, Andrew N Rosenbaum, Stacy A Bernard, Manish J Gandhi, Shaji Kumar, Taxiarchis Kourelis, Atta Behfar, Alfredo L Clavell, Shannon M Dunlay, Robert P Frantz, Sudhir S Kushwaha, Naveen L Pereira, Yee Weng Wong, Richard C Daly, Philip J Spencer, Mauricio A Villavicencio Theoduloz, Barry A Boilson.
       BACKGROUND: Human leukocyte antigen (HLA) sensitization is a significant barrier to transplantation for many patients. Daratumumab has proven safety and tolerability in multiple myeloma. We hypothesized that daratumumab monotherapy could be an effective and safe desensitization strategy in highly sensitized patients awaiting cardiac transplantation.
    OBJECTIVES: The primary end-point of this trial was the scope of daratumumab in lowering HLA antibodies. Secondary end-points included presence of donor-specific antibody, incidence of cellular and antibody-mediated rejection (AMR) and cardiac allograft function.
    METHODS: Six consecutive highly sensitized patients were enrolled who had a calculated panel reactive antibody >50% using a mean fluorescence intensity (MFI) threshold >4,000 through a single antigen bead assay. Three completed the full 8 weeks of daratumumab therapy. HLA antibodies with MFI >10,000 were considered unacceptable for donor offers. All patients received weekly doses of 1,800 mg daratumumab and 30,000 units hyaluronidase subcutaneously for a planned total of 8 weeks.
    RESULTS: There was a significant reduction in HLA class I and class II antibodies by the time of heart transplantation. Daratumumab was well tolerated and without any serious adverse events. By the time of this publication, 5 of the total of 6 patients enrolled have been successfully transplanted. None of the patients enrolled experienced AMR and maintain normal cardiac allograft function.
    CONCLUSIONS: Daratumumab monotherapy may be a safe and effective desensitization strategy in highly sensitized patients who are otherwise eligible for heart transplantation and considered too ill for other desensitization strategies.
    Keywords:  CD38; cardiac transplantation; daratumumab; desensitization; human leukocyte antigen antibodies; plasma cells
    DOI:  https://doi.org/10.1016/j.healun.2025.01.021
  13. Eur J Pharmacol. 2025 May 20. pii: S0014-2999(25)00501-1. [Epub ahead of print] 177747
    Next generation Bruton's tyrosine kinase inhibitors - characterization of in vitro potency and selectivity.
    Robert Pulz, Daniela Angst, Bruno Cenni.
      Bruton's tyrosine kinase (BTK) mediates B cell receptor and Fc receptor signaling and is a key regulator of autoimmunity and allergy. A series of novel BTK inhibitors (BTKi) are currently in development for non-oncologic indications with covalent-irreversible (remibrutinib, evobrutinib, tolebrutinib, orelabrutinib), covalent-reversible (rilzabrutinib), and non-covalent reversible (fenebrutinib) binding modes. This study characterizes their in vitro potency and selectivity profiles under the same conditions to minimize assay differences across the different binding modes. Covalent BTKi showed human in vitro blood BTK binding in a time- and concentration-dependent manner with remibrutinib being the most potent and fastest in onset of action. Cellular BTK pathway inhibition was determined in human blood B cells and basophils, and for covalent BTKi correlated well with BTK binding. In contrast to the covalent-irreversible remibrutinib, the non-covalent reversible fenebrutinib showed rapid loss of cellular BTK inhibition after washout. Kinase selectivity was assessed in a binding screen across the human kinome, followed by quantification of binding affinities for a selection of kinases. BTKi ranked in their selectivity as follows (most selective to least): remibrutinib, fenebrutinib, evobrutinib, orelabrutinib, rilzabrutinib and tolebrutinib. These data suggest that next generation BTKi show important differences in their in vitro target binding and selectivity when compared under the same conditions.
    Keywords:  BTK inhibitor; evobrutinib; fenebrutinib; orelabrutinib; remibrutinib (LOU064); rilzabrutinib; tolebrutinib
    DOI:  https://doi.org/10.1016/j.ejphar.2025.177747
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