bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–08–30
eighteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Older Age, STAG2, and DNMT3A Mutations Predict Superior Posttransplant Survival in Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax Plus Hypomethylating Agents.
  2. Daratumumab, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: MAIA final survival analysis.
  3. Venetoclax with azacitidine and dexamethasone: Non-cytotoxic induction therapy for T-cell leukemia and mixed-phenotype leukemia.
  4. Epcoritamab with rituximab and lenalidomide as first-line treatment for follicular lymphoma (EPCORE NHL-2): an open-label, multicentre, phase 1/2 b trial.
  5. Venetoclax added to dose-adjusted EPOCH-R for newly diagnosed double-hit lymphomas: phase 2 results from ALLIANCE A051701, an open-label, randomised, controlled, phase 2-3 trial.
  6. Targeting the Menin-KMT2A Axis in AML: Translating Molecular Insights into Therapeutic Success.
  7. Continued remission maintained with decitabine monotherapy in an elderly patient with TP53 multi-hit acute myeloid leukemia relapsed after allogeneic transplantation.
  8. Nipocalimab for warm autoimmune hemolytic anemia: results from the phase 2/3 randomized, double-blind ENERGY study.
  9. Novel agents and evolving strategies in Waldenström macroglobulinemia: clinical trial updates from ASH 2025.
  10. Phase 1 Trial with Soquelitinib, a Selective ITK Inhibitor for Treatment of Relapsed/Refractory T Cell Lymphomas.
  11. Real-world effectiveness and safety of Zanubrutinib in Spanish patients with relapsed/refractory marginal zone lymphoma.
  12. Targeting CDK7 to overcome hypomethylating agent resistance in acute myeloid leukemia.
  13. Final results of a phase II study of the combination of azacitidine and ruxolitinib in patients with myelofibrosis.
  14. LTB-TREAT: A validated international prognostic model for time to treatment in low tumour burden follicular lymphoma.
  15. Long-term outcomes of vindesine or vincristine substitutions for vinblastine in classical Hodgkin lymphoma.
  16. Comparison of post-transplant cyclophosphamide and low-dose anti-thymocyte globulin with dose-dependent effects in mismatched unrelated donor transplantation.
  17. Vaporization trick enables 'tandem' solar cells to be made at lower temperatures.
  18. NFкB pathway suppression as a key driver of pacritinib response in high-risk myelofibrosis.
  1. Am J Hematol. 2026 Aug 23.
    Older Age, STAG2, and DNMT3A Mutations Predict Superior Posttransplant Survival in Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax Plus Hypomethylating Agents.
    Momna Warraich, Sudhesh Kumar, Mahnoor Fatima, Kristen McCullough, Aref Al-Kali, Hassan B Alkhateeb, Kebede H Begna, Abhishek Mangaonkar, Antoine N Saliba, Aasiya Matin, Mark R Litzow, William Hogan, Mithun V Shah, Mrinal M Patnaik, Animesh Pardanani, James Foran, Lisa Sproat, Nandita Khera, Ayalew Tefferi, Naseema Gangat.
      Venetoclax (Ven) plus hypomethylating agents (HMA) is standard frontline therapy for newly diagnosed AML (ND-AML) patients unfit for intensive chemotherapy and is also considered in younger, fit patients. However, consolidation with allogeneic stem cell transplant (ASCT) is often required to secure durable remission. The current study examines posttransplant outcomes in patients with ND-AML treated with frontline Ven-HMA who subsequently underwent ASCT. A total of 111 ND-AML patients (58% male, 60% secondary/therapy-related, median age 70 years [range, 37-80]) received a median of 3 cycles of Ven-HMA. Mutations at the time of diagnosis included RUNX1 (18%), SRSF2 (17%), TP53 (16%), ASXL1, IDH2, K/NRAS, TET2 (14% each), STAG2 (11%), DNMT3A (8%). All patients were in CR/CRi at the time of transplant including 88% after Ven-HMA. Measurable residual disease (MRD) by flow cytometry was detectable in 18/76 (24%) patients. Donors were mostly HLA-matched unrelated (75%); 51% receiving fludarabine/melphalan conditioning and 67% posttransplant cyclophosphamide. At a median follow-up of 15 months, 42 (38%) of patients have died and 18 (16%) experienced posttransplant relapse. Median posttransplant survival was not reached (NR), with 1-, 2-, 3-year survival rates of 69%/60%/57%, respectively. On multivariate analysis, age ≥ 65 years, STAG2 mutation (STAG2MUT), and DNMT3AMUT were associated with superior posttransplant survival. Patients were stratified into low- (0-1 point), intermediate- (2 points), and high-risk (3 points); age < 65 years, STAG2 wild type, and DNMT3A wild type, with 3-year survival rates of 89%, 59%, and 19%, respectively (p < 0.01). Taken together, age, STAG2MUT and DNMT3AMUT stratified posttransplant survival in Ven-HMA treated patients with ND-AML.
    Keywords:  graft‐versus‐host disease; karyotype; measurable residual disease; mutations; nonrelapse mortality; relapse‐free survival
    DOI:  https://doi.org/10.1002/ajh.70480
  2. Leukemia. 2026 Aug 24.
    Daratumumab, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: MAIA final survival analysis.
    Thierry Facon, Shaji K Kumar, Robert Z Orlowski, Nizar Bahlis, Philippe Moreau, Hartmut Goldschmidt, Supratik Basu, Cyrille Hulin, Sonja Zweegman, Katja Weisel, Aurore Perrot, Caroline Jacquet, Noopur Raje, Salomon Manier, Ajai Chari, Markus Hansson, Mohamad Mohty, Michel Delforge, Torben Plesner, Gordon Cook, Xavier Leleu, Hang Quach, Christopher P Venner, Mourad Tiab, Margaret Macro, Laurent Frenzel, George Wang, Huiling Pei, Kasey Bolyard, Robin Carson, Fredrik Borgsten, Saad Z Usmani.
      In previous analyses of MAIA, daratumumab plus lenalidomide/dexamethasone (D-Rd) significantly improved progression-free survival and overall survival (OS) versus lenalidomide/dexamethasone (Rd) in transplant-ineligible newly diagnosed multiple myeloma (NDMM). We report results on long-term OS and subsequent antimyeloma therapies from the MAIA final analysis. A protocol amendment (July 20, 2021) led to a long-term extension of MAIA, during which patients were followed for OS. A total of 737 patients were randomized to D-Rd (n = 368) or Rd (n = 369). At a median follow-up of 89.3 months (range, 0.0-102.2; interquartile range, 85.3-93.0), median OS was 90.3 months (95% confidence interval [CI], 80.8-not estimable [NE]) with D-Rd versus 64.1 months (56.0-70.8) with Rd (hazard ratio [HR], 0.67; 95% CI, 0.55-0.82); estimated 7-year OS rates were 53.1% (95% CI, 47.8-58.2) and 39.3% (34.1-44.5), respectively. Median time to subsequent antimyeloma treatment was not reached (95% CI, 84.1-NE) for D-Rd versus 42.4 months (33.5-50.6) for Rd (HR, 0.51; 95% CI, 0.41-0.63; P < 0.0001). Death due to adverse events occurred in 84 patients (D-Rd, n = 44/364 [12%]; Rd, n = 40/365 [11%]). With >7 years of follow-up, D-Rd demonstrated a new benchmark for median OS (7.5 years) in transplant-ineligible NDMM, further supporting frontline D-Rd use to maximize survival.
    DOI:  https://doi.org/10.1038/s41375-026-03097-9
  3. Ther Adv Hematol. 2026 ;17 20406207261480378
    Venetoclax with azacitidine and dexamethasone: Non-cytotoxic induction therapy for T-cell leukemia and mixed-phenotype leukemia.
    Yutian Lei, Xiaoli Zhao, Huijun Huang, Limin Duan, Ji Xu, Kourong Miao, Huihui Zhao, Chun Qiao, Ming Hong, Sixuan Qian, Lei Fan, Yu Zhu.
       Background: T-lineage acute leukemias are aggressive malignancies for which treatment options are limited.
    Objectives: This study evaluated the efficacy and safety of a non-cytotoxic regimen combining venetoclax, azacitidine, and dexamethasone (VAD) as first-line induction therapy for T-cell acute lymphoblastic leukemia (T-ALL) and T/myeloid mixed-phenotype acute leukemia (T-Myeloid MPAL).
    Design: We retrospectively analyzed the clinical parameters and survival data of 11 patients with newly-diagnosed T-ALL or T-Myeloid MPAL who received the VAD regimen.
    Methods: The complete remission (CR) rate and adverse events were assessed. Kaplan-Meier curves were constructed to evaluate survival outcomes.
    Results: Among 11 patients (7 with early T-cell precursor [ETP] ALL, 2 with T-Myeloid MPAL, and 2 with non-ETP T-ALL), the overall CR rate after one cycle of VAD therapy was 90.9%, with 45.5% achieving measurable residual disease (MRD) negativity by flow cytometry. The historically poor-prognosis ETP-ALL subgroup showed an 85.7% CR rate (6/7), while both T-Myeloid MPAL cases attained MRD negativity. No tumor lysis syndrome or treatment-related mortality occurred. Over a median follow-up of 358 days, all 5 patients who received transplantations remained relapse-free.
    Conclusion: The VAD regimen demonstrated a high response rate and favorable safety, enabling effective transplantation bridging with avoidance of conventional cytotoxic therapy.
    Keywords:  T-lineage acute leukemia; non-cytotoxic chemotherapy; venetoclax
    DOI:  https://doi.org/10.1177/20406207261480378
  4. Lancet Haematol. 2026 Sep;pii: S2352-3026(26)00198-5. [Epub ahead of print]13(9): e614-e625
    Epcoritamab with rituximab and lenalidomide as first-line treatment for follicular lymphoma (EPCORE NHL-2): an open-label, multicentre, phase 1/2 b trial.
    Lorenzo Falchi, Joost S P Vermaat, Joshua D Brody, Lori Leslie, Fritz Offner, Jacob Haaber Christensen, Marcel Nijland, David Belada, Björn Engelbrekt Wahlin, Kristina Drott, Pilar Gomez Prieto, Kateřina Kopečkova, Alejandro Martín García-Sancho, Jian P Mei, Işıl Altıntaş, Malene Risum, Aidan Reilly, Jun Zou, Pau Abrisqueta.
       BACKGROUND: Chemotherapy-free regimens, such as rituximab and lenalidomide, are attractive first-line treatment options for follicular lymphoma, but combinations providing deeper, more durable responses are needed. We aimed to assess 3-year activity and safety of epcoritamab, a subcutaneously administered CD3 × CD20 bispecific antibody, plus rituximab-lenalidomide as first-line treatment for follicular lymphoma.
    METHODS: EPCORE NHL-2 is an open-label, phase 1b/2, clinical trial. Arm 6 of the study was conducted at 20 hospitals in six countries in Europe (Spain, the Netherlands, Czech Republic, Sweden, Belgium, and Denmark) and the USA in patients aged 18 years and older with CD20+, histologically confirmed grade 1-3A follicular lymphoma, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received intravenous rituximab 375 mg/m2 once per week in cycle 1 (28 days per cycle) and every 4 weeks in cycles 2-6; oral lenalidomide 20 mg daily on days 1-21 of cycles 1-12; and subcutaneous epcoritamab in a two-step-up dosing regimen of a 0·16 mg priming dose, followed by a 0·8 mg intermediate dose, then full 48 mg doses in cycle 1, 48 mg once per week in cycle 2, and 48 mg every 4 weeks in subsequent cycles for up to 2 years. The primary endpoint was investigator-assessed overall response rate by Lugano Response Criteria for Malignant Lymphoma. The full analysis set and the safety set included all patients who received one or more doses of trial drug. This study is registered with ClinicalTrials.gov (NCT04663347) and is ongoing (closed to new participants).
    FINDINGS: Between Sept 23, 2021, and May 3, 2022, 45 patients were assessed for eligibility in Arm 6, 41 of whom were eligible and included in the full analysis and safety sets. 21 (51%) of 41 patients were male and 20 (49%) were female; 27 (66%) of patients were White, one (2%) was Asian, one (2%) was of another race, and 12 (29%) did not have race reported. At a median follow-up of 35·9 months (IQR 35·8-36·6) the overall response rate was 95% (95% CI 84-99; 39 of 41 patients). The most common grade 3-4 adverse events were neutropenia (20 [49%] of 41 patients), infections (12 [29%]), COVID-19 (six [15%]), and alanine aminotransferase increase (five [12%]). Serious adverse events occurred in 29 (71%) patients, including cytokine release syndrome (13 [32%]), serious infections (13 [32%]; one grade 2), pyrexia (three [7%]), organising pneumonia (one [2%]), pleural effusion (one [2%]), pneumonitis (one [2%]), pulmonary embolism (one [2%]), maculopapular rash (two [5%]), toxic skin eruption (one [2%]), atrial fibrillation (one [2%]), diarrhoea (one [2%]), dehydration (one [2%]), ovarian epithelial cancer (one [2%]), cerebrovascular accident (one [2%]), and thrombophlebitis (one [2%]). Treatment-related deaths occurred in three (7%) patients due to septic shock, progressive multifocal leukoencephalopathy, and COVID-19.
    INTERPRETATION: Epcoritamab plus rituximab-lenalidomide showed high activity in first-line treatment for follicular lymphoma, with 95% of patients having a response over 3 years of follow-up, supporting this treatment regimen as a promising approach that warrants further analysis to ascertain its role in this setting.
    FUNDING: Genmab and AbbVie.
    DOI:  https://doi.org/10.1016/S2352-3026(26)00198-5
  5. Lancet Haematol. 2026 Sep;pii: S2352-3026(26)00191-2. [Epub ahead of print]13(9): e626-e638
    Venetoclax added to dose-adjusted EPOCH-R for newly diagnosed double-hit lymphomas: phase 2 results from ALLIANCE A051701, an open-label, randomised, controlled, phase 2-3 trial.
    Jeremy S Abramson, Susan Geyer, Sharmila Giri, Levi Pederson, Ann Hudson, Eric D Hsi, Neha Mehta-Shah, Patrick M Reagan, Richard L Deming, Richard F Little, Steven Gore, Shira N Dinner, Anusha Vallurupalli, Daniel J Landsburg, Brad Kahl, Jonathan W Friedberg, Nancy L Bartlett, John P Leonard.
       BACKGROUND: High-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6, known as double-hit lymphoma, is a highly aggressive malignancy with poor outcomes after standard chemoimmunotherapy. We aimed to study whether the addition of the BCL2-inhibitor venetoclax to chemoimmunotherapy in patients with double-hit lymphoma resulted in superior efficacy compared with chemotherapy alone.
    METHODS: ALLIANCE A051701 is an open-label, randomised, controlled, phase 2-3 trial in separate cohorts of patients with double-hit lymphoma and patients with double-expressor lymphoma. In this analysis, we report phase 2 results from the double-hit lymphoma cohort. Patients aged 18-80 years with newly diagnosed double-hit lymphoma and Eastern Cooperative Oncology Group (ECOG) performance status 0-2 were recruited from 41 hospitals and outpatient clinics in the USA. Patients were randomly assigned (1:1) to receive DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) either alone (DA-EPOCH-R group) or with venetoclax (DA-EPOCH-R plus venetoclax group) using permuted block randomisation schedule. All patients and investigators were aware of group assignment. DA-EPOCH-R was administered on a 21-day schedule for up to six total cycles. Venetoclax was given as 600 mg by mouth daily on days 4-8 of cycle 1 and on days 1-5 of cycles 2-6. The primary endpoint was progression-free survival in the modified intent-to-treat population inclusive of all eligible patients with centrally confirmed double-hit lymphoma. The safety analysis population consisted of all evaluable patients who received at least one dose of protocol treatment. This trial is registered with ClinicalTrials.gov (NCT03984448) and is closed to enrolment.
    FINDINGS: 36 patients were randomly assigned to the DA-EPOCH-R group and 37 to the DA-EPOCH-R plus venetoclax group between Oct 22, 2019, and Sept 18, 2020. Median age was 65 years (IQR 56-73) and baseline demographic factors were well balanced between groups, with 30 (45%) female and 36 (55%) male patients. Most patients (59 [89%]) were white, two (3%) were Asian, one (2%) was Black or African American, and four (6%) had unknown or unreported ethnicity. The majority of patients had MYC-BCL2 double-hit lymphoma (59 [89%] patients), advanced stage disease (57 [86%] patients), and high-intermediate/high-risk IPI score (42 [64%] patients). Median follow-up was 34·7 months (IQR 30·1-36·8). Median progression-free survival was 28·4 months (95% CI 5·2-not estimable) in the DA-EPOCH-R group (n=30) and 7·7 months (95% CI 4·7-NE) in the DA-EPOCH-R plus venetoclax group (n=36; hazard ratio [HR] 1·13, 95% CI 0·53-2·37; p=0·75). Deaths on treatment occurred in one (3%) patient in the DA-EPOCH-R group (due to dyspnoea; possibly related to treatment) and six (17%) patients in the DA-EPOCH-R plus venetoclax group (four due to sepsis [three at least possible related and one unrelated], two due to cardiac arrest [at least possibly related]), prompting early closure of the double-hit lymphoma cohort. The most common grade 3-4 non-haematological adverse event was febrile neutropenia, occurring in 15 (43%) of 35 patients in the DA-EPOCH-R plus venetoclax group and 11 (37%) of 30 patients in the DA-EPOCH-R group. The median overall survival has not been reached in either group. The 24-month overall survival estimates were 72% (95% CI 52-85) in the DA-EPOCH-R group compared with 52% (95% CI 33-68) in the DA-EPOCH-R plus venetoclax group (HR 2·49, 95% CI 1·03-6·04; p=0·038).
    INTERPRETATION: The addition of venetoclax to DA-EPOCH-R resulted in excess mortality, prompting early study closure. Robust accrual shows that prospective multicentre trials are feasible in double-hit lymphoma, and the outcomes in the DA-EPOCH-R group serve as a benchmark for future studies.
    FUNDING: National Cancer Institute of the National Institutes of Health.
    DOI:  https://doi.org/10.1016/S2352-3026(26)00191-2
  6. Clin Lymphoma Myeloma Leuk. 2026 Aug 01. pii: S2152-2650(26)00244-2. [Epub ahead of print]
    Targeting the Menin-KMT2A Axis in AML: Translating Molecular Insights into Therapeutic Success.
    Claudia Simio, Alessandra Vatteroni.
      Menin inhibitors (MIs) represent a novel class of targeted agents that disrupt the interaction between the nuclear protein menin and the KMT2A (MLL) complex, thereby interrupting a crucial oncogenic transcriptional program in acute myeloid leukemias (AML) with KMT2A rearrangements and NPM1 mutations. Robust preclinical data have shown that menin inhibition suppresses HOXA/MEIS1 expression, induces differentiation, and reduces the fitness of leukemic cells, including the stem-like compartment. These findings rapidly led to phase I/II clinical trials with oral MIs such as revumenib and ziftomenib, which demonstrated CR+CRh rates of 22% to 23% in refractory/relapsed patients, with conversion to measurable residual disease (MRD) negativity in 61% to 68% of responders and early use as a bridge to allogeneic transplantation. However, the median duration of response remains limited (approximately 4-5 months), suggesting that menin inhibition as monotherapy may be insufficient to ensure durable disease control. Key emerging clinical issues include specific adverse events (QTc prolongation in 12%-44%, differentiation syndrome in 10%-29%), drug-drug interactions mediated by CYP3A4 metabolism, resistance dynamics (on-target mutations in 39% of cases), and the definition of the optimal role in combination with venetoclax, hypomethylating agents, and intensive chemotherapy. This review synthesizes molecular mechanisms, preclinical and clinical data, discusses use within MRD-guided and transplant pathways, and proposes translational priorities for integrating MIs into future therapeutic paradigms, pending confirmation from randomized studies.
    Keywords:  Epigenetic therapy; KMT2A-rearranged AML; Menin inhibition; NPM1-mutated AML; Therapeutic Resistance
    DOI:  https://doi.org/10.1016/j.clml.2026.07.019
  7. Haematologica. 2026 Aug 27.
    Continued remission maintained with decitabine monotherapy in an elderly patient with TP53 multi-hit acute myeloid leukemia relapsed after allogeneic transplantation.
    Julian List, Etienne Sollier, Robin Benkelmann, Miriam Mozaffari Jovein, Christoph Plass, Jürgen Finke, Michael Lübbert.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2026.301209
  8. Blood. 2026 Aug 28. pii: blood.2026034036. [Epub ahead of print]
    Nipocalimab for warm autoimmune hemolytic anemia: results from the phase 2/3 randomized, double-blind ENERGY study.
    Bruno Fattizzo, Irina Murakhovskaya, Yasutaka Ueda, Doug Schlichting, Kristen Marie Sweet, Michael Zelasky, Jagriti Craig, Sophia G Liva, Jocelyn H Leu, Leona E Ling, Sheryl Pease, Amuche Anakor, Cathye Shu.
      Warm autoimmune hemolytic anemia (wAIHA) is a rare, life-threatening disease characterized by autoantibody-mediated destruction of red blood cells with no approved treatments. Nipocalimab, an immunoselective neonatal Fc receptor blocker, reduces circulating IgG levels, including autoantibodies implicated in wAIHA. The phase 2/3, randomized, 24-week, double-blind ENERGY study in participants with wAIHA evaluated nipocalimab 30 mg/kg IV q4w (n=38), 15 mg/kg IV q2w (n=38), and placebo (n=39). The primary endpoint, durable hemoglobin response (hemoglobin ≥10 g/dL and a ≥2 g/dL increase from baseline at 3 consecutive visits [≥28 days] starting by Week 16, without rescue therapy), achieved statistical significance for nipocalimab 30 mg/kg IV q4w (23.7% [9/38]; 1-sided P=0.015) but not 15 mg/kg IV q2w (21.1% [8/38]; P=0.044; not significant) versus placebo (7.7% [3/39]). Improvement in FACIT-Fatigue score at Week 24 (key secondary endpoint) was observed with nipocalimab, with mean (SD) improvement of 3.4 (7.29) points (nominal P=0.007) for 30 mg/kg IV q4w and 1.2 (6.07) (nominal P=0.267) for 15 mg/kg IV q2w versus 0.6 (3.42) for placebo. Mean percent (SD) reduction in average daily prednisone dose (key secondary endpoint) was 15.1% (28.2) for nipocalimab 30 mg/kg IV q4w (nominal P=0.039) and 14.0% (30.4) for 15 mg/kg IV q2w (nominal P=0.055) versus 3.9% (16.33) for placebo. The safety profile was consistent with the known safety profile of nipocalimab and with wAIHA-associated risks. Overall, in the double-blind ENERGY study, nipocalimab demonstrated rapid hemoglobin response and nominal improvements in fatigue that were maintained over 24 weeks, with no new safety findings in wAIHA. NCT04119050.
    DOI:  https://doi.org/10.1182/blood.2026034036
  9. Exp Hematol Oncol. 2026 Aug 28. pii: 83. [Epub ahead of print]15(1):
    Novel agents and evolving strategies in Waldenström macroglobulinemia: clinical trial updates from ASH 2025.
    Yujing Liang, Xinyi Deng, Ziwen Wang, Chuanmiao Xie, Lie Zheng, He Huang, Shaohan Yin, Huageng Huang.
      Waldenström macroglobulinemia (WM) is a rare, indolent lymphoplasmacytic lymphoma characterized by bone marrow infiltration of IgM-secreting lymphoplasmacytic cells and associated with the MYD88(L265P) mutation in over 90% of cases. This mutation drives constitutive NF-κB signaling through aberrant MYD88 oligomerization, rendering WM dependent on BCR-proximal kinases including BTK for survival. Despite significant therapeutic advances over the past decade, including the established efficacy of BTK inhibitors, proteasome inhibitors, and anti-CD20 monoclonal antibodies in both frontline and relapsed settings, unmet needs persist-particularly regarding treatment durability, acquired resistance to covalent BTK inhibitors via C481S mutations, and the need for chemotherapy-free alternatives. The 2025 American Society of Hematology (ASH) Annual Meeting featured several pivotal clinical trials addressing these challenges, spanning optimized immunochemotherapy combinations in treatment-naive disease, next-generation BTK-targeted agents for relapsed/refractory cases including non-covalent inhibitors that bypass C481S-mediated resistance and protein degraders that eliminate both BTK kinase activity and scaffolding function, and emerging modalities including BCL2 inhibitors that exploit the apoptotic dependence of WM cells on BCL2 family proteins, MALT1 inhibitors that target downstream NF-κB signaling, and CD19-targeted antibody-drug conjugates and cellular therapies.
    Keywords:  Clinical research; Relapse or refractory; Treatment-naive; Waldenström macroglobulinemia
    DOI:  https://doi.org/10.1186/s40164-026-00821-0
  10. Blood. 2026 Aug 25. pii: blood.2026034704. [Epub ahead of print]
    Phase 1 Trial with Soquelitinib, a Selective ITK Inhibitor for Treatment of Relapsed/Refractory T Cell Lymphomas.
    Richard A Miller, Ning Ding, John C Reneau, Yuqin Song, Dok Hyun Yoon, Tatyana A Feldman, Costas K Yannakou, Won Seog Kim, Robin Gasiorowski, Youn H Kim, Michael S Khodadoust, Dejan Radeski, Pratyush Giri, Ho-Jin Shin, Sung-Soo Yoon, Neha Mehta-Shah, Oleg E Akilov, Amit S Khot, Nagendra Prasad Sungala, Suresh Mahabhashyam, Ryan A Wilcox.
      Despite advances in the molecular characterization of mature T and NK cell lymphomas, outcomes for these patients is poor especially those with relapsed/refractory (R/R) disease. These tumors possess mutations that often result in tonic T cell receptor (TCR) signaling and an immunosuppressive tumor microenvironment. Interleukin-2-inducible T cell kinase (ITK) plays an important role in TCR signaling and T cell differentiation. Soquelitinib is a covalent oral selective ITK inhibitor that blocks Th2 differentiation while sparing Th1 cells (Th1 skewing). We conducted a phase 1 trial with soquelitinib for the treatment of R/R peripheral T cell lymphomas to determine safety, target occupancy and antitumor activity. A dose escalation design was followed by an expansion cohort to confirm dosing and identify predictive characteristics. Seventy-five patients were enrolled. No dose-limiting toxicities were observed with doses up to 600mg BID and target occupancy exceeding 80% was established for 200mg BID dose. At the 200mg BID dose, number of prior lines of therapy was found to affect antitumor activity as durable complete and partial responses were seen in 37% patients with 1-3 prior therapies; no responses were seen in patients with >3. Objective and durable tumor responses were observed in various histologic subtypes. Blood and tumor biopsies indicated that soquelitinib treatment leads to Th1 skewing, reduction of T cell exhaustion and blockade of Th2 cells. These studies demonstrate soquelitinib is active in T cell lymphomas with a mechanism related to effects on malignant T cells and/or normal T effector cells. Trial registration: NCT03952078 at www.ClinicalTrials.gov.
    DOI:  https://doi.org/10.1182/blood.2026034704
  11. Blood Adv. 2026 Aug 25. pii: bloodadvances.2026020480. [Epub ahead of print]
    Real-world effectiveness and safety of Zanubrutinib in Spanish patients with relapsed/refractory marginal zone lymphoma.
    Fernando Martin-Moro, Ana Muntanola Prat, Xabier Gutierrez Lopez De Ocariz, Maria Sofia Vazquez Diaz, Lucía Morais, Itxaso Amarika, Ramón Diez-Feijóo, Mariana Bastos-Oreiro, Beatriz de la Cruz Benito, Javier Marco Ayala, Sergio Ramos Cillan, Ana Jiménez-Ubieto, Pablo Galindo-Navarro, Juan Gonzalo Correa, Esperanza Lavilla Rubira, Cristina García-Herce, Miriam Moreno, Eva Domingo-Domenech, Nazaret Domínguez, Aranzazu Alonso, Maria José Otero, Alessandra Comai, Maria Luisa Bengochea Casado, Carolina Villegas, Norma C Gutierrez, Rafael Lluch García, Sara Fernández-Luis, Joan-Alfons Soler, Jimena Cannata-Ortiz, Ángeles Medina, Sofía Martín-Consuegra, Marta Aceituno, Paola Villafuerte Gutierrez, Dunia de Miguel Llorente, José-María Arguiñano, Javier López-Marín, Lucia Villalon, Horacio Gulino, Armando López-Guillermo, Antonio Salar.
      There is no established standard treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL). Zanubrutinib was approved in this setting based on the phase II MAGNOLIA trial. We retrospectively evaluated the characteristics and outcomes of 118 real-world patients in Spain with R/R MZL treated with zanubrutinib after at least one prior anti-CD20-based regimen. The median age at zanubrutinib initiation was 75 years, and 56% were female. MZL subtypes included splenic (55.3%), MALT (18.9%), nodal (19.8%), and non-classifiable (6%). The median number of prior lines of therapy (LoT) was 1.5 (range 1-7); 26% were refractory to the immediately preceding line, and 59% were POD24 to frontline. Thirty-one patients (26.3%) would not have met MAGNOLIA eligibility criteria, 68% had cardiovascular comorbidities, and 28% were receiving antithrombotic therapy. The overall and complete response rates were 76% and 22.2%, respectively, with no differences according to MZL subtype, age, POD24, or MAGNOLIA eligibility. Fewer prior LoT were associated with higher and deeper responses. With a median follow-up of 14 months, 1-year progression-free and overall survival were 79.4% and 86.8%, respectively. Zanubrutinib responders and patients with stable disease presented better outcomes than cases with progressing disease (p < 0.01). Adverse events (AEs) were reported in 34.1% of patients (grade ≥ 3 in 14.4%). MAGNOLIA-ineligible patients experienced a higher incidence of AEs, and bleeding events were more frequent among patients receiving anticoagulant therapy (p = 0.04). Overall, zanubrutinib demonstrated favorable effectiveness and safety in real-world R/R MZL, with improved outcomes when administered earlier in the disease.
    DOI:  https://doi.org/10.1182/bloodadvances.2026020480
  12. Blood Res. 2026 Aug 24. pii: 45. [Epub ahead of print]61(1):
    Targeting CDK7 to overcome hypomethylating agent resistance in acute myeloid leukemia.
    Bon-Kwan Koo, Eun-Ji Choi, Ju Hyun Moon, Ji Yun Kim, Hyunkyung Park, Joon Young Hur, Han-Seung Park, Yunsuk Choi, Jung-Hee Lee, Je-Hwan Lee, Eun-Hye Hur.
       PURPOSE: Hypomethylating agents (HMAs), such as azacitidine and decitabine, are widely used in elderly or medically unfit patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). However, most patients eventually develop primary or acquired resistance and outcomes following HMA failure remain poor, particularly in transplantation-ineligible patients. This study evaluated the efficacy of CDK7 inhibition as a therapeutic strategy for overcoming HMA resistance in vitro.
    METHODS: HMA-resistant AML cells (MOLM/AZA-1 and MOLM/DEC-5) were generated to evaluate the therapeutic activity of the CDK7 inhibitor, YPN-005. Cell viability was assessed using a CellTiter-Glo assay. Western blotting was performed to examine the dysregulation of DNA methyltransferases (DNMTs) and apoptotic markers. Cell cycle distribution and apoptosis were evaluated using flow cytometry. Transcriptomic changes were analyzed using quantitative reverse transcription polymerase chain reaction.
    RESULTS: YPN-005 demonstrated potent growth-inhibitory effects in HMA-resistant AML cells, with an efficacy comparable to that observed in parental MOLM-13 cells. Mechanistically, CDK7 inhibition reduced DNMT expression and decreased the phosphorylation of RNA polymerase II (Ser2/5/7). YPN-005 significantly induced apoptosis, as evidenced by increased Annexin V positivity and the activation of PARP and caspase-3. Notably, CD40 expression was markedly upregulated at both the transcript and protein levels.
    CONCLUSION: CDK7 inhibition effectively induces apoptosis in HMA-resistant AML cells by suppressing RNA polymerase II phosphorylation and downregulating aberrant DNMT expression. Furthermore, the induction of CD40 suggests a potential role for CDK7 blockade in modulating immunophenotypic features. These findings support CDK7 inhibition as a promising therapeutic strategy for overcoming resistance to epigenetic therapies in patients with AML/MDS.
    Keywords:  Acute myeloid leukemia; Cyclin dependent kinase 7 inhibitor; Hypomethylating agent resistance
    DOI:  https://doi.org/10.1007/s44313-026-00162-1
  13. Haematologica. 2026 Aug 27.
    Final results of a phase II study of the combination of azacitidine and ruxolitinib in patients with myelofibrosis.
    Sankalp Arora, Jayastu Senapati, Victoria Chu, Naveen Pemmaraju, Prithviraj Bose, Elias Jabbour, Tapan Kadia, Jing Ning, Dyana Saenz, Linghsa Zhou, Habiba Halim, Yesid Alvarado, Maro Ohanian, Courtney DiNardo, Koichi Takahashi, Nitin Jain, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero, Lucia Masarova, Naval Daver.
      Monotherapy with JAK2 inhibitors reduces splenomegaly and symptom burden but has limited effect on natural progression of myelofibrosis. We conducted a phase 2 clinical trial evaluating the combination of azacitidine (AZA) and ruxolitinib (RUX) in myelofibrosis. The interim analysis with 46 patients (median follow-up 28 months) demonstrated a response rate of 72%. We now report the final results of this clinical trial. The study primary endpoint was objective response rate by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. From 3/2013 to 10/2021, 61 patients were treated (median age 66 years; range, 46-87 years). By baseline blast count, 54 patients had chronic phase disease (.
    DOI:  https://doi.org/10.3324/haematol.2026.301178
  14. Br J Haematol. 2026 Aug 27.
    LTB-TREAT: A validated international prognostic model for time to treatment in low tumour burden follicular lymphoma.
    Luani Barge, Lachlan Webb, Anita Pelecanos, Niamh Waters, Ross Salvaris, Sam Lai, Tessa Potezny, Helen Cashman, Caitlyn Nguyen-Ngo, Denise Lee, Costas K Yannakou, Nada Hamad, Adrien Chauchet, Sylvain Choquet, Cédric Rossi, Adélie Herbin, Lukshe Kanagaratnam, Cyrielle Rodier, Constantine S Tam, Abir Bhattacharyya, Chan Y Cheah, Eliza A Hawkes, Kirk Morris, Eric Durot, Joshua Tobin, Greg Hapgood.
      Watchful waiting (WW) in low tumour burden follicular lymphoma (LTB FL) defers treatment. There is a need to develop a model to predict time to treatment (TTT). We aimed to develop and externally validate a model for TTT in LTB FL. We conducted a retrospective analysis across eight centres within the Australasian Lymphoma Alliance. Two hundred and twenty-nine patients were included between 2004 and 2022 with a median follow-up of 5.0 years (range 0.5-17.8 years) and a median age was 64 years. All patients were Group d'Etude des Lymphomes Folliculaires (GELF) negative and managed with WW. Elevated lactate dehydrogenase and >4 nodal areas were independent prognostic factors associated with shorter TTT. These factors formed a prognostic model identifying three groups: low 59% (median TTT 6.34 years), intermediate 36% (median TTT 4.08 years), high risk 5% (median TTT 1.49 years) (p < 0.001). There was a higher incidence of serious complications among risk groups (low 7.5% vs. intermediate 13.3% vs. high 25%; p = 0.096). The prognostic value of the LTB-TREAT model was confirmed in an external validation cohort. The low-risk group is predicted to have a prolonged TTT with WW and a high-risk group is predicted to experience early progression in whom treatment should be considered.
    Keywords:  low tumour burden follicular lymphoma; prognostic models; time to treatment
    DOI:  https://doi.org/10.1111/bjh.70748
  15. Chin Med J (Engl). 2026 Aug 24.
    Long-term outcomes of vindesine or vincristine substitutions for vinblastine in classical Hodgkin lymphoma.
    Yu Fang, Min Bai, Yao Liu, Jianhong Wang, Hui Geng, Liyun He, Xiaoxi Zhou, Fang Zhu, Weicheng Zheng, Mingyi Di, Kai Hu, Huimin Liu, Fuling Zhou, Huiqiang Huang, Yi Xia, Rui Cao, Yafen Xiong, Weiying Gu, Yu Xie, Xiongpeng Zhu, Shaoxiong Wang, Jing Yang, Jingwei Yu, Chenchen Wang, Rong Liang, Liping Su, Qingqing Cai.
      
    DOI:  https://doi.org/10.1097/CM9.0000000000004265
  16. Br J Haematol. 2026 Aug 27.
    Comparison of post-transplant cyclophosphamide and low-dose anti-thymocyte globulin with dose-dependent effects in mismatched unrelated donor transplantation.
    Donor/Source Working Group of the Japan Society for Transplantation and Cellular Therapy
      
    Keywords:  anti‐thymocyte globulin; mismatched unrelated donor transplantation; post‐transplant cyclophosphamide
    DOI:  https://doi.org/10.1111/bjh.70791
  17. Nature. 2026 Aug 26.
    Vaporization trick enables 'tandem' solar cells to be made at lower temperatures.
    Ulrich W Paetzold, Paul Fassl.
      
    Keywords:  Chemistry; Energy; Materials science
    DOI:  https://doi.org/10.1038/d41586-026-02469-6
  18. Br J Haematol. 2026 Aug 28.
    NFкB pathway suppression as a key driver of pacritinib response in high-risk myelofibrosis.
    R Van Dijck, M Ter Borg, B van der Holt, A E C Broers, M D Hazenberg, J J Cornelissen, N P M Schaap, E de Pater, P A W Te Boekhorst.
      
    Keywords:  NFkB; myelofibrosis; pacritinib
    DOI:  https://doi.org/10.1111/bjh.70811
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