bims-hemali Biomed News
on Hematologic malignancies
Issue of 2025–06–29
fourteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Five-year molecular response and overall survival with first- and second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia in the chronic phase: a prospective, observational study - SIMPLICITY.
  2. Asciminib for Philadelphia chromosome-positive leukemias
  3. Treatment-Free Remission in Chronic Myeloid Leukemia: Revisiting the "W" Questions.
  4. Treatment of Philadelphia positive acute lymphoblastic leukemia.
  5. More than myeloma: the trouble with "normal" plasma cells.
  6. Lower-intensity chemo-immunotherapy with cladribine, low-dose cytarabine, venetoclax and blinatumomab produces high response rates in patients with BCR::ABL1-negative B-cell / myeloid mixed phenotype acute leukemia.
  7. Intensive chemotherapy after hypomethylating agent and venetoclax in adult acute myeloid leukemia.
  8. Efficacy and Safety of Ropeginterferon Alfa-2b in Low-Risk Polycythemia Vera.
  9. Elderly Acute Lymphoblastic Leukemia: Low-Dose Chemotherapy and Immunotherapy Combinations.
  10. NO (nitric oxide) to priapism with hydroxyurea and tadalafil.
  11. Augmented use of L-asparaginase markedly improves AYA ALL outcomes: FBMTG prospective MRD2014 study.
  12. Use of second-line and beyond maintenance therapies in adult patients with primary immune thrombocytopenia in Europe: a parallel study of six prospective multicenter national registries.
  13. First-in-world Trojan horse drug offered to multiple myeloma patients in England.
  14. Targeting Senescence: A Review of Senolytics and Senomorphics in Anti-Aging Interventions.
  1. Leuk Lymphoma. 2025 Jun 22. 1-10
    Five-year molecular response and overall survival with first- and second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia in the chronic phase: a prospective, observational study - SIMPLICITY.
    Michael J Mauro, Rüdiger Hehlmann, Loretta A Williams, Stuart L Goldberg, Mauricette Michallet, Carlo Gambacorti-Passerini, Derek Tang, Irene S DeGutis, Ali McBride, Lori Parsons, Monica Montelongo, Jorge E Cortes.
      SIMPLICITY (NCT01244750) was an observational study evaluating first-line (1 L) tyrosine kinase inhibitors (TKIs; dasatinib, nilotinib, imatinib) in patients with chronic myeloid leukemia in the chronic phase in routine clinical practice. At data cutoff (January 28, 2020), 810 prospective US patients were included/analyzed (dasatinib, 302; nilotinib, 264; imatinib, 244). Within 5 years, 95.4% of patients (dasatinib, 96.5%; nilotinib, 93.5%; imatinib, 95.9%) had major molecular response (BCR::ABL1 ≤ 0.1%), and 79.2% (dasatinib, 79.8%; nilotinib, 81.7%; imatinib, 75.9%) deep molecular response (MR4.5; BCR::ABL1 < 0.0032%) demonstrating major improvement during the study period. Of 734 patients followed for 5 years, 5-year overall survival rate was 89.8% (dasatinib, 92.9%; nilotinib, 88.6%; imatinib, 87.0%); similar to that in randomized studies. Patients who switched treatment had a poorer outcome regardless of TKI, indicating that non-kinase domain mutations may play a role. Despite missing data on outcomes in routine care, these results demonstrate excellent response and survival rates.
    Keywords:  Chronic-phase chronic myeloid leukemia; SIMPLICITY; molecular response; observational study; overall survival; routine care; treatment switch; tyrosine kinase inhibitor
    DOI:  https://doi.org/10.1080/10428194.2025.2495369
  2. Haematologica. 2025 06 26.
    Asciminib for Philadelphia chromosome-positive leukemias
    Timothy P Hughes, Deborah L White, David T Yeung.
      Twenty-five years after the introduction of imatinib, we have entered a new era of therapy for Chronic Myeloid Leukemia (CML). Despite the development of second and third generation (2G and 3G) tyrosine kinase inhibitors (TKIs), their impact have been incremental in improving outcomes for CML patients. While frontline use of 2G TKIs have improved molecular response rates and reduced progression to blast phase, there has been no improvement in overall survival compared to imatinib, likely due to the higher toxicity and consequent higher non CML-related mortality. Imatinib remains the most prescribed therapy for CML worldwide, despite it being the least potent TKI and most prone to resistance and progression. Asciminib, the first STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor, binds to the myristoyl pocket of BCR::ABL1. Its specificity minimises off-target toxicity which enables asciminib to finally break this frustrating link between potency and toxicity. After a decade of clinical trials, both in patients with resistance and intolerance to two or more TKIs, and more recently in the frontline setting, asciminib is fulfilling its early promise of a more rapid and reliable pathway to long-term disease control with minimal toxicity. There are however some unexpected challenges when using asciminib that require further investigation. In this Spotlight we review the key studies and outline the potential impact and current limitations of this first STAMP inhibitor in the CML setting and in other leukemias where ABL1 or ABL2 is the key target.
    DOI:  https://doi.org/10.3324/haematol.2024.286798
  3. Eur J Haematol. 2025 Jun 23.
    Treatment-Free Remission in Chronic Myeloid Leukemia: Revisiting the "W" Questions.
    Antonella Bruzzese, Ernesto Vigna, Enrica Antonia Martino, Nicola Amodio, Caterina Labanca, Francesco Mendicino, Eugenio Lucia, Virginia Olivito, Fortunato Morabito, Massimo Gentile.
      Chronic myeloid leukemia (CML) has undergone a transformation from a fatal disease to a chronic, manageable condition with the advent of tyrosine kinase inhibitors (TKIs), particularly imatinib. This shift has significantly improved survival rates, and for some patients, achieving deep molecular response (DMR) has made treatment-free remission (TFR) a feasible goal. However, the ability to sustain TFR remains a challenge, primarily due to the persistence of leukemia stem cells (LSCs), which are inherently resistant to TKIs and contribute to relapse after treatment cessation. The barriers to TFR include not only the persistence of LSCs but also the complex biology of resistance mechanisms. Attempts to overcome these barriers through TKI rotation, second-generation TKIs, or strategies targeting the tumor microenvironment have shown limited success. Third-generation TKIs like ponatinib and novel agents such as asciminib and olverembatinib offer promising therapeutic alternatives, particularly for patients with the T315I mutation. However, their use is constrained by safety concerns and limited availability, especially in low-resource settings. Patient selection remains a crucial aspect of achieving TFR, as not all patients with DMR sustain remission after discontinuation of therapy. Factors such as age, immune profile, and measurable residual disease levels significantly influence relapse risk. Identifying reliable clinical and molecular predictors of successful TFR is essential for optimizing treatment strategies and improving outcomes. The concept of the "W" questions-who, when, why, what, and where-frames the future of TFR in CML. Who should be selected for TFR? When should TFR be pursued? Why are some patients successful in achieving and sustaining TFR, while others relapse? What strategies can enhance the likelihood of TFR success, such as novel therapies, combination treatments, and patient-specific approaches? Where should these strategies be implemented to ensure equitable access, particularly in resource-limited settings? This review highlights the progress made in CML treatment, emphasizes the need for precision medicine to personalize TFR strategies, and stresses the importance of answering the fundamental "W" questions to advance the field. Future research must focus on refining predictive models, exploring new therapeutic options, and expanding access to treatments to ensure equitable benefits for all CML patients globally.
    Keywords:  CML; TFR; TKI
    DOI:  https://doi.org/10.1111/ejh.70000
  4. Acta Haematol. 2025 Jun 24. 1-22
    Treatment of Philadelphia positive acute lymphoblastic leukemia.
    Anna Torrent, Josep Maria Ribera.
      Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has historically been associated with poor prognosis and limited therapeutic options. Over the past two decades, however, the treatment paradigm has markedly shifted. The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, and ponatinib, has revolutionized frontline therapy, significantly improving remission rates and long-term survival. These agents, when combined with reduced-intensity chemotherapy or even with corticosteroids, have enabled less toxic regimens, particularly beneficial for older or unfit patients. The implementation of measurable residual disease (MRD) monitoring has emerged as a pivotal tool for risk stratification and therapeutic decision-making. Consequently, the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), considered a cornerstone of curative treatment, is being re-evaluated in patients achieving sustained deep molecular responses. More recently, immunotherapeutic strategies-including the bispecific T-cell engager blinatumomab and chimeric antigen receptor (CAR) T-cell therapies-have emerged as effective alternatives to conventional chemotherapy and TKIs. This review outlines the major advances in the management of Ph+ ALL, emphasizing the move toward more personalized, targeted, and less toxic treatment approaches.
    DOI:  https://doi.org/10.1159/000547026
  5. Blood. 2025 Jun 26. 145(26): 3066-3067
    More than myeloma: the trouble with "normal" plasma cells.
    Ross S Firestone, Francesco Maura.
      
    DOI:  https://doi.org/10.1182/blood.2025028750
  6. Haematologica. 2025 Jun 26.
    Lower-intensity chemo-immunotherapy with cladribine, low-dose cytarabine, venetoclax and blinatumomab produces high response rates in patients with BCR::ABL1-negative B-cell / myeloid mixed phenotype acute leukemia.
    Roberta S Azevedo, Wei-Ying Jen, Danielle Hammond, Fadi G Haddad, Alexis Geppner, Ghayas C Issa, Koji Sasaki, Jayastu Senapati, Elias Jabbour, Farhad Ravandi, Hagop Kantarjian, Tapan M Kadia.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2025.287932
  7. Blood Neoplasia. 2024 Dec;1(4): 100038
    Intensive chemotherapy after hypomethylating agent and venetoclax in adult acute myeloid leukemia.
    Kuo-Kai Chin, Yannis Valtis, Andriy Derkach, Meira Yisraeli Salman, Leora Boussi, Jenna Ciervo, Mark B Geyer, Jae H Park, Martin S Tallman, Jacob L Glass, Aaron D Goldberg, Eytan M Stein.
      The combination of a hypomethylating agent (HMA) and venetoclax (VEN) is approved for adults aged >75 years with newly diagnosed acute myeloid leukemia (AML) as well as those ineligible for intensive chemotherapy (IC). HMA/VEN is increasingly substituted for IC in adults with AML aged <75 years, particularly in those with adverse cytogenetic and molecular features. When patients fail to respond or relapse after HMA/VEN, the utility of salvage IC is largely unknown. We performed a retrospective single-institution study and identified 46 patients who received IC after HMA/VEN, including 24 patients who received HMA/VEN as their first treatment for AML. This population had complete remission (CR)/CR with incomplete count recovery (CRi)/morphologic leukemia-free state rate of 37%, CR/CRi rate of 28%, and a median overall survival (mOS) of 7.2 months (95% confidence interval, 5.0-10.3). Patients who relapsed after an initial response to HMA/VEN and subsequently received IC were more likely to achieve a CR/CRi than those refractory to HMA/VEN (50% vs 19%; P = .04), although there was no statistically significant difference in survival (mOS, 8.8 vs 5.4 months; P = .64). Age >65 years predicted poorer survival (mOS, 4.3 vs 10.6 months; P < .001). IC after HMA/VEN should be further studied and chosen with caution.
    DOI:  https://doi.org/10.1016/j.bneo.2024.100038
  8. Cancer Res Treat. 2025 Jun 26.
    Efficacy and Safety of Ropeginterferon Alfa-2b in Low-Risk Polycythemia Vera.
    Ji Yun Lee, Sung-Soo Yoon, Deok-Hwan Yang, Sang Kyun Sohn, Seug Yun Yoon, Soo-Mee Bang, Gyeong-Won Lee, Chul Won Choi, Eun-Ji Choi, June-Won Cheong, Young Hoon Park, Sung-Eun Lee.
       Purpose: Conventional management of low-risk polycythemia vera (PV), consisting of phlebotomy and aspirin, often fails to adequately control symptoms and hematologic parameters. This study evaluated the efficacy and safety of ropeginterferon alfa-2b (Ropeg) in low-risk PV patients requiring cytoreductive therapy.
    Materials and Methods: In this sub-analysis of an open-label, multicenter trial, 42 patients received Ropeg for 48 weeks. The primary endpoint was a reduction in phlebotomy frequency, while secondary endpoints included complete hematologic response (CHR), changes in JAK2V617F allele burden, and safety.
    Results: Among 42 patients, Ropeg significantly reduced mean phlebotomy frequency per year from 3.0 to 0.5 (p < 0.05) and improved CHR rates (69.1% at 48 weeks). The JAK2V617F allele burden decreased, and hydroxyurea-naïve patients showed better responses. The most frequently reported treatment-related adverse events included elevated liver enzymes and alopecia. Most adverse events were mild or moderate, with no grade 4 or 5 events reported.
    Conclusion: These findings suggest that Ropeg is a promising treatment option for low-risk PV by effectively reducing the need for phlebotomy and demonstrating efficacy and safety.
    Keywords:  Phlebotomy; Polycythemia vera; Ropeginterferon alfa-2b
    DOI:  https://doi.org/10.4143/crt.2025.552
  9. Clin Lymphoma Myeloma Leuk. 2025 Jun 06. pii: S2152-2650(25)00201-0. [Epub ahead of print]
    Elderly Acute Lymphoblastic Leukemia: Low-Dose Chemotherapy and Immunotherapy Combinations.
    Perrine Moyer, Aude-Marie Fourmont, Lucie Freiman, Philippe Rousselot, Patrice Chevallier.
      There is an unmet medical need for the treatment of elderly patients with acute lymphoblastic leukemia (ALL), as only a minority of them achieves long-term survival with current anti-ALL chemotherapy. Here, the recent management of these patients is discussed, including current approaches and future directions, as novel agents developed for refractory/relapsed ALL are now being incorporated into front-line therapies with very promising results. The manuscript will sequentially consider Philadelphia chromosome (Ph) negative ALL, then Ph+ and finally T-ALL. Accordingly, novel strategies using chemo-free approaches and new drugs such as inotuzumab ozogamicin, blinatumomab, venetoclax, tyrosine kinase inhibitors and CAR T-cells will be discussed.
    Keywords:  Acute lymphoblastic leukemia; Blinatumomab; Immunotherapy; Inotuzumab; Older
    DOI:  https://doi.org/10.1016/j.clml.2025.06.001
  10. Blood. 2025 Jun 26. 145(26): 3063-3064
    NO (nitric oxide) to priapism with hydroxyurea and tadalafil.
    Kenneth I Ataga.
      
    DOI:  https://doi.org/10.1182/blood.2025028905
  11. Blood Neoplasia. 2024 Sep;1(3): 100033
    Augmented use of L-asparaginase markedly improves AYA ALL outcomes: FBMTG prospective MRD2014 study.
    Koji Nagafuji, Toshihiro Miyamoto, Tetsuya Eto, Tomohiko Kamimura, Koji Kato, Yasuhiko Miyazaki, Atsushi Wake, Kentaro Kohno, Ken Takase, Yutaka Imamura, Naoyuki Uchida, Kazuki Tanimoto, Noriaki Kawano, Toshiro Kurokawa, Yukio Kondo, Yoshikiyo Ito, Tomoaki Fujisaki, Junichi Tsukada, Koji Yonemoto, Toshinori Hori, Koichi Akashi.
      The enhanced utilization of native L-asparaginase (L-Asp) aims to improve treatment outcomes for adult patients with non-Philadelphia chromosome (Ph) acute lymphoblastic leukemia (ALL). In this measurable residual disease 2014 (MRD2014) study, we modified our protocol to include an augmented dose of native L-Asp. Compared with former MRD2008, the total dose of L-Asp was raised from 36 000 U/m2 to 232 000 U/m2 in patients aged 16 to 35 and from 36 000 U/m2 to 132 000 U/m2 in patients aged 36 to 65 years. Adult patients with ALL were enrolled between January 2014 and December 2019 based on the following eligibility criteria: non-L3 ALL, age 16 to 65 years, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate liver and kidney functions (serum bilirubin ≤ 2.0 mg/dL; serum creatinine ≤ 2.0 mg/dL). The median follow-up time was 1128 days (range, 35-2400). A total of 81 patients with non-Ph ALL (40 males and 41 females; median age, 39 years [range, 16-64]) in whom MRD status was assessed were included. Complete remission was achieved in 72 patients (89%). The probability of 3-year event-free survival (EFS) and overall survival (OS) in these patients were 55% and 72%, respectively. The outcomes for patients aged 16 to 35 years demonstrated remarkable improvement. The 3-year EFS of MRD2008 at 45% significantly increased to 71% for MRD2014. Our study unequivocally demonstrated the beneficial effects of augmented use of L-Asp in this adolescent and young adult population. This trial was registered at UMIN Clinical Trials Registry as #UMIN000012382.
    DOI:  https://doi.org/10.1016/j.bneo.2024.100033
  12. Haematologica. 2025 Jun 26.
    Use of second-line and beyond maintenance therapies in adult patients with primary immune thrombocytopenia in Europe: a parallel study of six prospective multicenter national registries.
    Guillaume Moulis, Frederick Chen, Giuseppe Carli, Waleed Ghanima, Karolin Trautmann-Grill, Thomas Stauch, Alexandra Schifferli, Haroon Miah, Manuela Rueter, Lisanna Ghiotto, Riccardo Tomasello, Annabell Georgi, Vickie McDonald, Francesco Zaja, Heidi Hassel Pettersen, Thomas Kühne, Maria Luisa Lozano, Tomás José González-López, Drew Provan, Marc Michel, Nichola Cooper, Francesco Rodeghiero.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2025.287408
  13. Lancet Oncol. 2025 Jun 19. pii: S1470-2045(25)00373-0. [Epub ahead of print]
    First-in-world Trojan horse drug offered to multiple myeloma patients in England.
    Talha Burki.
      
    DOI:  https://doi.org/10.1016/S1470-2045(25)00373-0
  14. Biomolecules. 2025 Jun 13. pii: 860. [Epub ahead of print]15(6):
    Targeting Senescence: A Review of Senolytics and Senomorphics in Anti-Aging Interventions.
    Timur Saliev, Prim B Singh.
      Cellular senescence is a fundamental mechanism in aging, marked by irreversible growth arrest and diverse functional changes, including, but not limited to, the development of a senescence-associated secretory phenotype (SASP). While transient senescence contributes to beneficial processes such as tissue repair and tumor suppression, the persistent accumulation of senescent cells is implicated in tissue dysfunction, chronic inflammation, and age-related diseases. Notably, the SASP can exert both pro-inflammatory and immunosuppressive effects, depending on cell type, tissue context, and temporal dynamics, particularly in early stages where it may be profibrotic and immunomodulatory. Recent advances in senotherapeutics have led to two principal strategies for targeting senescent cells: senolytics, which selectively induce their apoptosis, and senomorphics, which modulate deleterious aspects of the senescence phenotype, including the SASP, without removing the cells. This review critically examines the molecular mechanisms, therapeutic agents, and clinical potential of both approaches in the context of anti-aging interventions. We discuss major classes of senolytics, such as tyrosine kinase inhibitors, BCL-2 family inhibitors, and natural polyphenols, alongside senomorphics including mTOR and JAK inhibitors, rapalogs, and epigenetic modulators. Additionally, we explore the biological heterogeneity of senescent cells, challenges in developing specific biomarkers, and the dualistic role of senescence in physiological versus pathological states. The review also highlights emerging tools, such as targeted delivery systems, multi-omics integration, and AI-assisted drug discovery, which are advancing precision geroscience and shaping future anti-aging strategies.
    Keywords:  aging; anti-aging therapy; cellular senescence; longevity; senescence-associated secretory phenotype (SASP); senolytics; senomorphics
    DOI:  https://doi.org/10.3390/biom15060860
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