bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–08–09
fifteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. [Recent advances in the treatment of chronic myeloid leukemia].
  2. Talquetamab in patients with relapsed/refractory multiple myeloma: 3-year follow-up of the phase 1/2 MonumenTAL-1 study.
  3. Contemporary Management of Relapsed or Refractory Chronic Lymphocytic Leukemia.
  4. [Recent advances and future perspectives in the treatment of chronic lymphocytic leukemia].
  5. [Recent advances and future perspectives in the treatment of newly diagnosed multiple myeloma].
  6. Clonal and genomic determinants of e1a2 BCR::ABL1 chronic myeloid leukemia: A Fi-LMC study.
  7. Emerging agents and regimens for myeloproliferative neoplasms: updates from ASH 2025 Annual Meeting.
  8. First-line treatment with epcoritamab in combination with bendamustine plus rituximab induces sustained remissions beyond 3 years in patients with follicular lymphoma.
  9. Bruton tyrosine kinase inhibitors plus chemoimmunotherapy in previously untreated younger mantle cell lymphoma patients: Single-centre clinical outcomes.
  10. [Recent advances and future perspectives in the treatment of mantle cell lymphoma].
  11. [Recent advances and future perspectives in the treatment of classical Hodgkin lymphoma].
  12. Drugging smart: molecular glue degraders rise in T-ALL.
  13. [Recent advances and future perspectives in the treatment of NK/T-cell lymphoma].
  14. STAT3 inhibition eradicates multiple myeloma stem-like cells and induces immunogenic cell death.
  15. Boosting HSC functions: l-carnitine takes center stage.
  1. Rinsho Ketsueki. 2026 ;67(7): 711-715
    [Recent advances in the treatment of chronic myeloid leukemia].
    Seiichiro Katagiri.
      The introduction of tyrosine kinase inhibitors (TKIs) has substantially improved outcomes for chronic-phase chronic myeloid leukemia (CML-CP). Furthermore, the development of ABL myristoyl pocket inhibitors that target specific molecular pathways has enabled adoption of treatment strategies with fewer adverse events. However, the clinical significance of somatic mutations in genes other than ABL1 in treatment resistance is attracting increasing attention. Additionally, novel TKIs and STAMP inhibitors are under development, and are expected to further improve CML management. This article summarizes the frequency and clinical impact of somatic mutations in CML-CP and reviews promising novel TKIs and STAMP inhibitors.
    Keywords:  Chronic myeloid leukemia; STAMP inhibitors; Somatic mutations; Tyrosine kinase inhibitors
    DOI:  https://doi.org/10.11406/rinketsu.67.711
  2. Blood. 2026 Aug 06. pii: blood.2025031994. [Epub ahead of print]
    Talquetamab in patients with relapsed/refractory multiple myeloma: 3-year follow-up of the phase 1/2 MonumenTAL-1 study.
    Leo Rasche, Carolina Schinke, Cyrille Touzeau, Monique C Minnema, Niels van de Donk, Paula Rodriguez-Otero, Maria-Victoria Mateos, Jing Christine Ye, Chalmer Tomlinson, Deeksha Vishwamitra, Indrajeet Singh, Xiang Qin, Michela Campagna, Tara Masterson, Veronique Vreys, Bonnie W Lau, Jaszianne Tolbert, Thomas Renaud, Christoph Heuck, Ajai Chari.
      Talquetamab is the first and only approved bispecific antibody targeting G protein-coupled receptor class C group 5 member D (GPRC5D) for treatment of relapsed/refractory multiple myeloma based on results from the phase 1/2 MonumenTAL-1 study. Here, we report efficacy and ongoing safety from MonumenTAL-1 with 3 years of follow-up. Patients naïve to T-cell redirection therapy (TCR) received talquetamab 0.4 mg/kg weekly (n=143) or 0.8 mg/kg every other week (n=154); a separate cohort received prior TCR (n=78, either talquetamab dose). Median follow-up was 38, 31, and 30 months in the 3 cohorts, respectively, as of September 2024. Overall response rate was 67-74% and complete response or better rate was 33-42%. Median progression-free survival was 7.5, 11.2, and 7.7 months, and median overall survival (OS) was 34.0 months, not reached, and 28.3 months (36-month OS rates 49.3%, 60.8%, and 44.6%), in the 3 cohorts, respectively. The most common adverse events (AEs) were cytokine release syndrome (73-79%; grade 3/4, 0.6-2.1%), taste changes (72-76%), and infections (61-78%; grade 3/4, 21-26%). Ataxia/balance disorders occurred in 5.3% of patients (no grade 4/5 events). Dose reduction and discontinuation rates due to AEs remained low; no patients died due to talquetamab-related AEs. With 3 years of follow-up, talquetamab continued to demonstrate high rates of deep and durable responses. The long-term safety profile was comparable to previous results and continued to show lower risk of high-grade infections relative to approved BCMA-targeting bispecific antibodies. NCT03399799 (phase 1) and NCT04634552 (phase 2).
    DOI:  https://doi.org/10.1182/blood.2025031994
  3. J Clin Oncol. 2026 Aug 07. JCO2600428
    Contemporary Management of Relapsed or Refractory Chronic Lymphocytic Leukemia.
    Mathias Castonguay, John F Seymour.
      Relapsed or refractory (RR) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) presents increasing therapeutic complexity in the era of targeted agents. Frontline use of covalent Bruton tyrosine kinase inhibitors (cBTKis) and venetoclax-based fixed-duration (FD) or minimal residual disease-guided regimens has led to deeper remissions, yet many patients will eventually require subsequent therapy. Management of first relapse should integrate clinical status, prior therapy, progression kinetics, and assessment for Richter transformation, along with genomic re-evaluation (particularly acquired resistance mutations and TP53 aberrations).Multiple effective options exist for relapsing disease. Second-generation cBTKi (acalabrutinib, zanubrutinib) continuous therapy provides durable disease control with improved tolerability over ibrutinib, whereas continuous venetoclax monotherapy or FD venetoclax-rituximab achieves high response rates and prolonged remission, with retreatment feasible for selected patients. Noncovalent BTKis (ncBTKis) such as pirtobrutinib offer meaningful activity in patients previously exposed to cBTKi. Cellular therapies, particularly lisocabtagene maraleucel, have demonstrated substantial efficacy in heavily pretreated patients, and allogeneic hematopoietic cell transplantation remains an option for select individuals with double-class refractory disease. Emerging therapies-including BTK degraders, next-generation BCL2 inhibitors, and bispecific antibodies-will likely reshape the therapeutic landscape for RR CLL/SLL. With broadening treatment options for RR CLL/SLL, optimal sequencing requires consideration of disease biology, depth and duration of prior response, comorbidities, toxicity profiles, patient preferences, and logistical factors. As therapeutic options expand, individualized treatment planning and clinical trial participation remain essential for improving outcomes in RR CLL/SLL.
    DOI:  https://doi.org/10.1200/JCO-26-00428
  4. Rinsho Ketsueki. 2026 ;67(7): 786-792
    [Recent advances and future perspectives in the treatment of chronic lymphocytic leukemia].
    Kensuke Kojima.
      The treatment of chronic lymphocytic leukemia (CLL) has rapidly evolved from traditional chemoimmunotherapy to molecular targeted therapies. Current recommended first-line treatment options include covalent BTK inhibitor (cBTKi: ibrutinib, acalabrutinib±obinutuzumab, and zanubrutinib)-based regimens and BCL2 inhibitor (BCL2i: venetoclax)-containing regimens (venetoclax+obinutuzumab and venetoclax+ibrutinib). The former approach relies on continuous treatment with cBTKi for long-term disease control, and the latter is a time-limited approach using BCL2i aiming for long-term treatment-free remission. Molecular and genetic features of CLL, performance status, comorbidities, social support systems, and patient preference are considered in treatment selection for CLL. The non-covalent BTK inhibitor pirtobrutinib has recently been approved for patients with relapsed or refractory CLL who have previously been treated with a cBTKi. The durability of responses to initial and subsequent treatment of CLL has greatly extended life expectancy, and newer agents including BTK degraders, next-generation BCL2 inhibitors, novel antibodies (antibodies against BAFF, CD19, or ROR1, along with CD3×CD20 bispecific antibodies), and chimeric antigen receptor T-cell therapies should further improve quality of life for all patients.
    Keywords:  BCL2 inhibitor; BTK inhibitor; Chronic lymphocytic leukemia; Molecular targeted therapy
    DOI:  https://doi.org/10.11406/rinketsu.67.786
  5. Rinsho Ketsueki. 2026 ;67(7): 771-779
    [Recent advances and future perspectives in the treatment of newly diagnosed multiple myeloma].
    Tomotaka Suzuki.
      First-line treatment strategies for multiple myeloma (MM) have undergone a major transformation with the introduction of anti-CD38 monoclonal antibodies, leading to substantial improvements in depth of response and survival outcomes regardless of transplant eligibility. Achieving complete response and minimal residual disease (MRD) negativity has become a realistic therapeutic goal, and durable disease control, or so-called functional cure, is now actively discussed. At the same time, treatment decision-making has become increasingly complex. In particular, for transplant-ineligible patients, optimal therapy selection requires comprehensive consideration of not only efficacy but also toxicity, treatment burden, frailty, and individual patient characteristics. This review summarizes recent advances in frontline therapy for newly diagnosed MM, focusing on anti-CD38-based quadruplet regimens and evolving maintenance strategies. In addition, it discusses future perspectives and unresolved challenges, including the introduction of BCMA-targeted immunotherapies into frontline settings, MRD-guided response-oriented treatment strategies, and the potential role of genomic information in risk stratification and therapeutic decision-making, with an emphasis on implications for real-world clinical practice in Japan.
    Keywords:  Anti-CD38 antibody; B-cell maturation antigen; Minimal residual disease; Multiple myeloma
    DOI:  https://doi.org/10.11406/rinketsu.67.771
  6. Hemasphere. 2026 Aug;10(8): e70454
    Clonal and genomic determinants of e1a2 BCR::ABL1 chronic myeloid leukemia: A Fi-LMC study.
    Fi‐LMC group
      The rarer p190 (e1a2) transcript in chronic myeloid leukemia (CML) is associated with atypical presentations; yet, its biological basis remains poorly understood. Using a cohort of 60 patients including 42 chronic phase patients age-matched 1:1 with 42 e13a2/e14a2 patients in the chronic phase, we investigated the clinical, genomic, and clonal features of e1a2 BCR::ABL1 CML. We identified 60 e1a2 BCR::ABL1 CML patients showing distinctive hematologic features including lower leukocyte and platelet counts and higher monocytosis (12.3% vs. 2.0%, P < 0.001). Additional somatic mutations were detected in 37/42 (88%) e1a2 BCR::ABL1 cases compared with 7/42 (17%) e13a2/e14a2 BCR::ABL1 cases. The mutational spectrum was dominated by ASXL1 and TET2, and closely resembled CMML-like profiles. Genomic breakpoint sequences of 34 e1a2 BCR::ABL1 cases showed that BCR and ABL1 coordinates were similar to those observed in 394 B-ALL. Longitudinal mutational tracking revealed two distinct clonal architectures. In 71% of patients, mutations disappeared with molecular response, consistent with BCR::ABL1 as the founding event. In contrast, 29% of patients had mutations with stable VAFs, while BCR::ABL1 transcript levels decreased after treatment, indicating that the fusion had been acquired within a pre-existing mutated clone. Single-cell genotyping experiments confirmed these clonal architectures. These patients frequently developed cytopenias under tyrosine kinase inhibitor therapy and half required red blood cell transfusions, reflecting persistence of the ancestral clone rather than BCR::ABL1-driven disease. These findings show that e1a2 BCR::ABL1 CML frequently arises within complex, premutated clonal backgrounds, providing a biological basis for its atypical presentation and heterogeneous treatment response.
    DOI:  https://doi.org/10.1002/hem3.70454
  7. Exp Hematol Oncol. 2026 Aug 03. pii: 69. [Epub ahead of print]15(1):
    Emerging agents and regimens for myeloproliferative neoplasms: updates from ASH 2025 Annual Meeting.
    Tiantian Zhang, Heng Jiang, Delong Liu.
      Current Myeloproliferative neoplasm (MPN) therapies provide meaningful symptom and event-risk control but are limited by infrequent molecular remissions, treatment-limiting cytopenias (particularly anemia), and continued reliance on non-mutation-directed cytoreduction or phlebotomy with attendant morbidity. At ASH 2025 Annual Meeting, multiple investigational strategies aimed to address these limitations, including clone-directed targeting (INCA033989), phlebotomy-sparing physiologic therapy (rusfertide), and epigenetic disease-modifying combinations (pelabresib). We summarized the latest updates on these emerging agents and regimens for MPNs from the 2025 ASH Annual Meeting.
    Keywords:  CALR; INCA033989; JAK2; Myeloproliferative neoplasm; Pelabresib; Rusfertide
    DOI:  https://doi.org/10.1186/s40164-026-00813-0
  8. Hemasphere. 2026 Aug;10(8): e70443
    First-line treatment with epcoritamab in combination with bendamustine plus rituximab induces sustained remissions beyond 3 years in patients with follicular lymphoma.
    Umberto Vitolo, Lorenzo Falchi, Per-Ola Andersson, Marcel Nijland, Fritz Offner, Sylvia Snauwaert, Jacob H Christensen, Michael R Clausen, Alexander Fosså, Pilar G Prieto, Eliza A Hawkes, Judit M Jørgensen, Yasmin H Karimi, Catharina Lewerin, Joost S P Vermaat, Björn E Wahlin, Poliana Patah, Christopher Morehouse, Malene Risum, Zhu Li, Jennifer Marek, Joshua D Brody.
      First-line (1L) bendamustine plus rituximab (BR) leads to high response rates in follicular lymphoma (FL), but maintaining durable remissions remains challenging. We report the 3-year follow-up from arm 3 of the phase 1b/2 EPCORE NHL-2 trial (NCT04663347) of epcoritamab, a subcutaneously administered CD3×CD20 bispecific antibody, combined with BR in patients with newly diagnosed FL. Twenty-five patients received epcoritamab plus BR, followed by epcoritamab monotherapy for up to 2 years. At a median follow-up of 41.3 months, the best overall response and CR rates were both 96%. The median time to CR was 1.5 (range 1-6) months. At 3 years, 87% of responders maintained CR. High CR rates were observed across subgroups, including 100% of patients with bulky disease (≥7 cm), 93% with Follicular Lymphoma International Prognostic Index score ≥3, and 100% with bone marrow involvement. The three-year progression-free survival and overall survival rates were 83% and 96%, respectively. Three patients progressed within 24 months of initiating treatment. Long-term data were consistent with prior reports and the known safety profiles of the individual agents, with no high-grade cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome events. Infections occurred in 92% of patients; COVID-19 was the most common (84%). Overall, 1L FL treatment with epcoritamab plus BR resulted in deep, durable responses beyond 3 years with a consistent safety profile. These results compare favorably with BR alone, although they require confirmation in further studies, and highlight the versatility of epcoritamab in combination with various standards of care and in improving outcomes in FL.
    DOI:  https://doi.org/10.1002/hem3.70443
  9. Br J Haematol. 2026 Aug 07.
    Bruton tyrosine kinase inhibitors plus chemoimmunotherapy in previously untreated younger mantle cell lymphoma patients: Single-centre clinical outcomes.
    Kelly Chung, Amanda Chron, Anita Kumar, Lisa Modelevsky, Ashlee Joseph, Lynnette Henshaw.
      
    Keywords:  Bruton tyrosine kinase inhibitors; mantle cell lymphoma
    DOI:  https://doi.org/10.1111/bjh.70732
  10. Rinsho Ketsueki. 2026 ;67(7): 751-756
    [Recent advances and future perspectives in the treatment of mantle cell lymphoma].
    Momoko Nishikori.
      Mantle cell lymphoma (MCL) is characterized by repeated relapses and gradual disease progression under conventional cytotoxic chemotherapy. Although a variety of chemotherapy regimens have been developed to improve outcomes, direct comparisons of efficacy across regimens evaluated in different clinical trials remain challenging because of the limited number of patients in each study and the biological heterogeneity of the disease. Consequently, a universally accepted standard therapy for MCL has yet to be established. In recent years, the introduction of Bruton's tyrosine kinase (BTK) inhibitors has markedly improved the prognosis of patients with MCL. In parallel, advances in the understanding of its molecular pathogenesis have provided deeper insights into the mechanisms of drug response and resistance, as well as potential synergistic effects with other therapeutic agents. Collectively, these developments are reshaping the clinical management of MCL. With the anticipated expansion of novel therapeutic approaches, including immunotherapies, MCL has emerged as a highly active and rapidly evolving field in both clinical practice and molecular research.
    Keywords:  Autologous stem cell transplantation; BTK inhibitors; Mantle cell lymphoma; TP53
    DOI:  https://doi.org/10.11406/rinketsu.67.751
  11. Rinsho Ketsueki. 2026 ;67(7): 757-770
    [Recent advances and future perspectives in the treatment of classical Hodgkin lymphoma].
    Nobuhiko Yamauchi.
      Classical Hodgkin lymphoma (cHL) is a highly curable malignancy, with long-term remission achieved in approximately 85% of patients with limited-stage disease and in about 70% of those with advanced-stage disease following first-line therapy. In limited-stage cHL, treatment is generally guided by appropriate risk stratification, and the combination of ABVD followed by radiotherapy has long constituted the therapeutic backbone. For advanced-stage disease, six cycles of brentuximab vedotin plus AVD (BV-AVD) are currently regarded as the standard first-line treatment, whereas six cycles of ABVD remains a reasonable option for older patients in whom treatment tolerability is a particular concern. In recent years, the results of large-scale clinical trials evaluating first-line regimens incorporating brentuximab vedotin (BV) or immune checkpoint inhibitors (IO), together with interim PET-adapted treatment strategies, have shown promise for further improving treatment outcomes while minimizing the use of radiotherapy. For relapsed or refractory disease, immunotherapeutic approaches, including CD30-directed CAR T-cell therapy, are under active development. In parallel, circulating tumor DNA (ctDNA) is emerging as a promising biomarker for minimal residual disease assessment, and ctDNA-based molecular classification has also been proposed. This review outlines the current status and unresolved challenges of first-line treatment for cHL and discusses future perspectives in this evolving field.
    Keywords:  Brentuximab vedotin combined with AVD; Circulating tumor DNA; Classic Hodgkin lymphoma; Interim PET-adapted therapy
    DOI:  https://doi.org/10.11406/rinketsu.67.757
  12. Blood. 2026 Aug 06. 148(6): 647-648
    Drugging smart: molecular glue degraders rise in T-ALL.
    Beat C Bornhauser.
      
    DOI:  https://doi.org/10.1182/blood.2026033893
  13. Rinsho Ketsueki. 2026 ;67(7): 780-785
    [Recent advances and future perspectives in the treatment of NK/T-cell lymphoma].
    Motoko Yamaguchi.
      Extranodal natural killer/T-cell lymphoma (ENKL) is a rare lymphoid malignancy that has historically poor outcomes when treated with conventional lymphoma chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). In the early 2000s, treatment strategies designed to overcome multidrug resistance were adopted. The RT-2/3DeVIC (radiotherapy, dexamethasone, etoposide, ifosfamide, carboplatin) for newly diagnosed localized ENKL and SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) chemotherapy for newly diagnosed advanced-stage or relapsed/refractory ENKL, developed through clinical trials, subsequently improved the prognosis of patients with ENKL in real-world clinical practice in Japan. However, two outcome studies have also highlighted the limitations of these approaches. More recently, therapeutic development for ENKL has shifted toward PD-1/PD-L1 inhibitor-based strategies, as well as molecularly targeted therapies informed by advances in basic research. This review summarizes the current treatment landscape for ENKL in Japan, describes therapeutic developments outside Japan and ongoing investigational approaches, and discusses future directions in ENKL treatment development.
    Keywords:  Anti-PD-1/PD-L1 antibodies; Chemoradiotherapy; L-asparaginase; NK/T-cell lymphoma
    DOI:  https://doi.org/10.11406/rinketsu.67.780
  14. Blood Sci. 2026 Sep;8(3): e00301
    STAT3 inhibition eradicates multiple myeloma stem-like cells and induces immunogenic cell death.
    Yuqian Sha, Wenyu Li, Yan Zhang, Tengyuan Liu, Mei Yuan, Wenya Wang, Jianquan Gu, Hai Cheng, Mingshan Niu, Peiyu Yang, Yao Yao.
      Signal transducer and activator of transcription 3 (STAT3) is a pivotal oncogenic driver in multiple myeloma (MM), and its constitutive activation promotes malignant plasma cell proliferation, survival, and drug resistance in the bone marrow microenvironment. Despite therapeutic advances, MM remains incurable due to persistent STAT3-driven tumorigenesis and the resilience of MM stem cells. We investigated the therapeutic potential of napabucasin (BBI608), a novel STAT3 inhibitor, in MM. Our data demonstrated that BBI608 potently suppressed MM cell proliferation in vitro and in vivo, while significantly impairing the clonogenic potential and inducing robust apoptosis. Mechanistically, BBI608 exhibited dual efficacy by targeting bulk tumor cells and eradicating the stem-like compartment of MM cells, thereby addressing a critical therapeutic challenge. Moreover, we revealed that BBI608 triggered immunogenic cell death (ICD) via the activation of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), which subsequently enhanced T-cell-mediated anti-tumor immunity. Our findings highlight STAT3 inhibition as a promising strategy to simultaneously eradicate MM cells, target stem cell reservoirs, and harness anti-tumor immunity, providing a robust rationale for the clinical translation of BBI608 in MM therapy.
    Keywords:  Cancer stem cells; ICD; Napabucasin; STAT3
    DOI:  https://doi.org/10.1097/BS9.0000000000000301
  15. Blood. 2026 Aug 06. 148(6): 642-644
    Boosting HSC functions: l-carnitine takes center stage.
    Marie-Dominique Filippi.
      
    DOI:  https://doi.org/10.1182/blood.2026034381
This page is being maintained by Thomas Krichel. It was last updated on 2026‒08‒09 at 8:36.