bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–08–23
29 papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Fixed-duration epcoritamab plus R-CHOP in newly diagnosed LBCL with IPI score 3-5: results from the EPCORE NHL-2 trial.
  2. Dual targeting of BCR::ABL1 and DNA methylation in advanced CML: A 3-year survival analysis of TKI-Azacitidine combination therapy.
  3. [Novel Treatment for Primary Central Nervous System Lymphoma].
  4. Sapablursen for Erythrocytosis Control in Patients with Polycythemia Vera.
  5. CD7 CAR-T cells eliminate chronic myeloid leukemia stem cells specifically and effectively.
  6. Sequential TKI Treatment in Patients With Chronic Phase Chronic Myeloid Leukemia Resistant to Frontline Nilotinib or Dasatinib Therapy. A Real-Life Survey From the Italian Campus CML Network.
  7. Second Line CD19 CAR-T vs Platinum Salvage and Autologous Stem Cell Transplant for Primary Mediastinal B-Cell Lymphoma.
  8. Dual MYC and GSPT1 Protein Degrader for MYC-Driven Hematologic Malignancies.
  9. Richter transformation: emerging immunologic strategies beyond chemoimmunotherapy.
  10. A tale of networking glycoproteins.
  11. Eltrombopag plus cyclosporine A for moderate aplastic anemia (EMAA): a placebo-controlled, double-blind, phase 3 trial.
  12. Ferroptosis in multiple myeloma: molecular mechanisms and therapeutic opportunities.
  13. Tripping the switch: p38 inhibition unlocks venetoclax and inotuzumab ozogamicin synergy.
  14. Real-world outcomes of venetoclax plus hypomethylating agents in unfit acute myeloid leukaemia: Results of the GIMEMA AML2320 trial.
  15. Histone deacetylase inhibitors as venetoclax-sensitising partners in acute myeloid leukaemia: Mechanisms, pharmacology and translational perspectives.
  16. BrECADD in three days: Implementation of a condensed intensive first-line regimen in Hodgkin lymphoma.
  17. Blood-based MALDI-TOF mass spectrometry versus bone marrow MRD for monitoring multiple myeloma: CASSIOPEIA study results.
  18. Making remissions last: the promise of maintenance in primary central nervous system lymphoma.
  19. Fracturing ferric carboxymaltose from the iron pharmacopeia.
  20. Weekly Metronomic Venetoclax and Decitabine/Cedazuridine in Acute Myeloid Leukemia Patient Declining Blood Transfusion.
  21. Danburstotug, an anti-PD-L1 antibody, in relapsed/refractory extra-nodal natural killer/T-cell lymphoma: The phase 2 DISTINKT study.
  22. Chronic Myeloid Leukemia Presenting With T-Lymphoid Blast Crisis in a Young Female With Marked Hyperleukocytosis: A Case Report.
  23. Drug Resistance in Multiple Myeloma: Tumor-Intrinsic Mechanisms and the Bone Marrow Microenvironment.
  24. Stability of c-Myc protein differentiates Ras oncogene addiction and MAPK pathway dependency in Ras-mutant multiple myeloma.
  25. Venetoclax in Combination With Chemo-Immunotherapy in Richter Transformation: A Real-Life Experience.
  26. American Society of Hematology 2026 Guidelines for Immune Thrombocytopenia (ITP): Initial and Second-Line Therapy in Adults with Primary ITP.
  27. NRAS knockdown reverses monocytic cell state and resensitizes resistant FLT3-AML cells to gilteritinib.
  28. Hypomethylating Therapy in VEXAS Syndrome: Disease Modification Beyond Bridging to Transplant.
  29. Novel targeted therapies for central nervous system involvement in chronic lymphocytic leukemia: A systematic review.
  1. Blood. 2026 Aug 11. pii: blood.2026033839. [Epub ahead of print]
    Fixed-duration epcoritamab plus R-CHOP in newly diagnosed LBCL with IPI score 3-5: results from the EPCORE NHL-2 trial.
    Lorenzo Falchi, Fritz Offner, Sven de Vos, Joshua D Brody, Daniel Morillo, Kim Linton, Sylvia Snauwaert, Michael Roost Clausen, Yasmin H Karimi, Catherine Thieblemont, Umberto Vitolo, Lori A Leslie, Mayur S Narkhede, Raúl Córdoba, Toshihiko Oki, Monica Wielgos-Bonvallet, Mina Khoshdeli, Yi Hao, Kimberly Archer, Malene Risum, David Belada.
      Patients with newly diagnosed large B-cell lymphoma (LBCL) and International Prognostic Index (IPI) scores ≥3 have inferior outcomes with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We evaluated efficacy and safety of epcoritamab plus R-CHOP in newly diagnosed LBCL in Arm 1 of the phase 1b/2 EPCORE NHL-2 trial. Adults with CD20+ LBCL and IPI scores 3-5 received R-CHOP (6 cycles) plus epcoritamab for a total of 1 year of treatment. Primary endpoint was investigator-assessed overall response rate (ORR). Key secondary endpoints included complete response (CR) rate, duration of CR (DOCR), progression-free survival (PFS), overall survival (OS), minimal residual disease (MRD) negativity, and safety. Forty-seven patients were treated. Median age was 64 years, 89% had Ann Arbor stage IV, and 53% had bulky disease (≥7 cm). ORR was 98% (95% CI, 89-100) and CR rate 85% (95% CI, 72-94). At median follow-up of 44.2 months, median DOCR, PFS and OS were not reached (NR; 95% CI, NR-NR); estimated 2-year PFS and OS rates were 80% (95% CI, 65-89) and 87% (95% CI, 73-94), respectively. MRD-negativity was achieved in 100% of MRD-evaluable patients. Most common adverse events were neutropenia (74%), anemia (72%), and cytokine release syndrome (CRS; 60%). CRS events were predominantly grade 1-2; all resolved. Epcoritamab plus R-CHOP induced high response rates in patients with newly diagnosed LBCL and IPI scores 3-5. These promising findings support the ongoing phase 3 evaluation of this treatment regimen. This trial was registered at ClinicalTrials.gov (NCT04663347).
    DOI:  https://doi.org/10.1182/blood.2026033839
  2. Ther Adv Hematol. 2026 ;17 20406207261474931
    Dual targeting of BCR::ABL1 and DNA methylation in advanced CML: A 3-year survival analysis of TKI-Azacitidine combination therapy.
    Zhuming Yang, Danlei Han, Renying Ge, Zhenhao Wang, Hanlin Du, Yigang Guo, Zhe Zhao, Li Liu, Jun Qin, Bangwei Yu, Jie Hu, Xiya Gui, Meifang Su, Shiming Chen, Daozi Jiang, Jing Zheng, Hongxiang Wang, Li Meng, Weiming Li, Zhenya Hong.
       Background: Advanced-phase chronic myeloid leukemia (CML) remains associated with poor outcomes despite advances in tyrosine kinase inhibitor (TKI) therapy, underscoring the need for more effective treatment approaches.
    Objectives: This multicenter study evaluated the efficacy and safety of tyrosine kinase inhibitor (TKI) plus azacitidine (with optional low-dose chemotherapy) in advanced-phase CML.
    Design: Prospective multicenter single-arm study.
    Methods: 41 patients with accelerated- (AP) or blast-phase (BP) CML received azacitidine 75 mg/m2/day for 7 days per 28-day cycle (6 cycles) plus TKIs selected by ABL1 mutation status; chemotherapy was added based on early response. Major hematologic response (MaHR) was the primary endpoint. The secondary endpoints included cytogenetic/molecular responses-major cytogenetic response (MCyR), major molecular response (MMR), and undetectable minimal disease (UMD) - along with progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were documented.
    Results: Among 36 evaluable patients (median age 51 years; range: 24-77; AP: 13, BP: 23) after excluding 5 noncompliant patients, 63.9% achieved MaHR, with a median response time of 1.33 months. The cumulative 3-year response rates were as follows: MCyR, 48.5%; MR2.0 (BCR::ABL1 IS ≤1%), 16.3%; MMR, 21.8%; and UMD, 14.2%. Patients maintained sustainable responses during follow-up. Four hematopoietic stem cell transplantation (HSCT) recipients maintained durable remission with TKI consolidation. At 28.1-month median follow-up, median OS was not reached and median PFS was 8.17 months; estimated 3-year OS and PFS rates were 50.3% and 41.1%, respectively. Elevated baseline WBC count and BCR::ABL1 transcript levels predicted poor survival. Hematologic toxicities of grade 3 or higher occurred in 55.6% of patients, including neutropenia (36.1%), thrombocytopenia (33.3%).
    Conclusion: TKI-azacitidine therapy demonstrated promising efficacy and acceptable tolerability in patients with advanced-phase CML and may represent a feasible treatment option for this high-risk population.
    Keywords:  DNA methylation; azacitidine; chronic myeloid leukemia; combination therapy; tyrosine kinase inhibitors
    DOI:  https://doi.org/10.1177/20406207261474931
  3. No Shinkei Geka. 2026 Jul;54(4): 802-810
    [Novel Treatment for Primary Central Nervous System Lymphoma].
    Nobuyoshi Sasaki.
      Primary central nervous system lymphoma (PCNSL) is a form of aggressive extranodal lymphoma confined to the central nervous system. Outcomes have substantially improved thanks to the introduction of high-dose methotrexate-based induction chemotherapy and consolidation strategies (including autologous stem cell transplantation); however, therapeutic challenges remain, particularly in elderly patients and those with relapsed or refractory disease. Recent genomic studies have indicates that PCNSL is characterized by frequent MYD88 and CD79B mutations, resulting in constitutive activation of the B-cell receptor and NF-κB signaling pathways, concurrent with an immunosuppressive tumor microenvironment. These insights provide a rationale for the development of targeted therapies and immunotherapies. Bruton's tyrosine kinase inhibitors and immunomodulatory drugs have shown promising activity in both relapsed and frontline settings, and are currently being evaluated in combination with maintenance strategies. CD19-directed chimeric antigen receptor T-cell therapy and CD20×CD3 bispecific antibodies have also emerged as potential therapeutic options for relapsed/refractory PCNSL, with encouraging efficacy and manageable toxicity profiles. This review summarizes the molecular pathogenesis of PCNSL, current standard treatments, and recent advances in targeted therapies and immunotherapeutic strategies that could improve treatment outcomes.
    DOI:  https://doi.org/10.11477/mf.030126030540040802
  4. Blood. 2026 Aug 18. pii: blood.2026033792. [Epub ahead of print]
    Sapablursen for Erythrocytosis Control in Patients with Polycythemia Vera.
    Jeanne M Palmer, Jonathan How, Prithviraj Bose, Pankit Vachhani, Adam J Mead, Jonathan Sillar, Aaron T Gerds, Angela G Fleischman, Caitlin M O'Neill, Ross Ian Baker, Ronald Hoffman, Shiangtung Jung, Jon L Ruckle, Keyvan Yousefi, Sanjay Bhanot, Terrance D Barrett, Ruben A Mesa.
      Polycythemia vera is characterized by erythrocytosis and increased risk of thrombosis. Sapablursen is an antisense oligonucleotide that suppresses transmembrane serine protease 6 (TMPRSS6), increases hepcidin production, and reduces iron availability for erythropoiesis. IMPRSSION; an ongoing phase 2a, randomized, open-label study includes patients meeting 2016 WHO criteria for polycythemia vera, requiring ≥3 phlebotomies within 6 months of screening and ≥1 phlebotomy within the last 12 weeks. Cohort A (120 or 80 mg) and Cohort B (40 mg) received sapablursen subcutaneously once every 4 weeks (Q4W). The primary efficacy endpoint was the reduction in phlebotomy frequency from baseline to weeks 17-37 in patients who received ≥1 dose. Forty-nine patients received ≥1 sapablursen dose (median age 61 years; 82% male). The baseline mean±SD weekly phlebotomy rate was 0.15±0.07 in Cohort A; 0.17±0.07 in Cohort B and was reduced by -0.10 (95%CI, -0.13, -0.07; n=32;p<0.0001) in Cohort A; -0.10 (95%CI, -0.14, -0.06; n=17;p=0.0001) in Cohort B. Sapablursen reduced the median (IQR) number of phlebotomies from 5.0 (3.0-6.0,Cohort A; 3.5-6.5,Cohort B) at baseline (26-weeks) to 0 (0-1.0) in the efficacy evaluation window (20-weeks) in Cohort A and 1.5 (0-2.5) in Cohort B. Most adverse events were mild or moderate; anemia and fatigue were most common. The mean change in MPN-SAF-TSS at week 37 was -6.21 points (95%CI: -10.56, -1.85, p=0.0052) in Cohort A; -2.71 points in Cohort B (95% CI: -8.33, 2.91, p=0.34). Sapablursen reduced phlebotomy need, improved symptoms, and was safe and well-tolerated in patients with polycythemia vera. (Funded by Ionis Pharmaceuticals; ClinicalTrials.gov: NCT05143957).
    DOI:  https://doi.org/10.1182/blood.2026033792
  5. Hematology. 2026 Dec 31. 31(1): 2719241
    CD7 CAR-T cells eliminate chronic myeloid leukemia stem cells specifically and effectively.
    Wenjing Zhang, Haobing Wang, Ling Tang, Yingjie Kong, Yong You, Xiaojian Zhu, Hongxiang Wang.
       OBJECTIVES: Leukemia stem cells (LSCs) in chronic myeloid leukemia (CML) are associated with disease recurrence and progression, cannot be eliminated by tyrosine kinase inhibitors (TKIs), and affect TKI discontinuation in CML patients. Chimeric antigen receptor T cells (CAR-T) therapy can eliminate tumor cells expressing specific antigens. CD7 is highly expressed on LSCs and can distinguish LSCs from normal hematopoietic stem cells (HSCs). This study explored the biological characteristics of CD7, and evaluated the effects of CD7 CAR-T cells on CD7+ CML tumor cells and CD7+ LSCs in vitro.
    METHODS: We examined CD7 expression in primary CML LSCs, constructed CD7-overexpressing K562 cells, and assessed the in vitro cytotoxicity, degranulation and cytokine secretion of CD7 CAR-T cells against CD7+ CML cells and CD34+CD7+ LSCs, along with the correlation between CD7 and TKI resistance.
    RESULTS: CD7+ CML tumor cells were resistant to TKI to a certain extent. This molecule appears to be relevant to the survival of LSCs in patients with CML receiving TKI-targeted therapy. In the in vitro co-culture system, CD7 CAR-T cells effectively eliminate CD7+ CML cells and LSCs and exhibit multiple immunological activities during the co-culture process.
    DISCUSSION: This study targets the key limitation of current CML treatment in that TKIs fail to eliminate LSCs, and confirms the correlation between CD7 and LSC survival, as well as the targeting potential of CD7 CAR-T for CML.
    CONCLUSION: This study showed that using CD7 CAR-T cells to specifically eliminate LSCs is effective and rational in vitro, which provides experimental evidence for LSC-targeted CML therapy and lays a foundation for subsequent in vivo and translational research.
    Keywords:  CD7; chimeric antigen receptor T cells (CAR-T); chronic myeloid leukemia (CML); leukemia stem cell; tyrosine kinase inhibitors, BCR-ABL1, immunotherapy, drug resistance
    DOI:  https://doi.org/10.1080/16078454.2026.2719241
  6. Clin Lymphoma Myeloma Leuk. 2026 Jul 24. pii: S2152-2650(26)00216-8. [Epub ahead of print]
    Sequential TKI Treatment in Patients With Chronic Phase Chronic Myeloid Leukemia Resistant to Frontline Nilotinib or Dasatinib Therapy. A Real-Life Survey From the Italian Campus CML Network.
    Gabriele Gugliotta, Mario Annunziata, Isabella Capodanno, Davide Rapezzi, Immacolata Attolico, Marianna Caramella, Iolanda D Vincelli, Antonella R Rossi, Mario Tiribelli, Alessandra Malato, Michele Cimminiello, Vincenzo Accurso, Massimiliano Bonifacio, Sara Galimberti, Giuseppina Loglisci, Elisabetta Abruzzese, Monica Bocchia, Antonella Gozzini, Micaela Bergamaschi, Maria C Miggiano, Agostino Tafuri, Grazia Sanpaolo, Anna R Scortechini, Monica Crugnola, Debora Luzi, Luigiana Luciano, Gianni Binotto, Roberto Latagliata, Fausto Castagnetti, Alessandro Allegra, Giorgina Specchia, Uros Markovic, Gianantonio Rosti, Robin Foà, Giuseppe Saglio, Massimo Breccia, Fabio Stagno.
       BACKGROUND: Limited information is available on the management and outcome of chronic myeloid leukemia (CML) patients who are resistant to first-line treatment with a second-generation tyrosine kinase inhibitor (2G-TKI).
    PATIENTS AND METHODS: We conducted a multicenter, real-world, retrospective analysis on 69 chronic phase (CP) CML patients who switched to second-line treatment in case of failure (according to the European LeukemiaNet 2020 recommendations) after first-line nilotinib or dasatinib.
    RESULTS: The median time to switch to second-line therapy was 15 months, and ponatinib was the most frequently used TKI (68%). As best molecular response (MR), 78% of patients achieved a BCR::ABL1IS transcript level <1%. The estimated 3-year cumulative incidence of MR3 was 69.4% (95% CI, 53.2%-84.2%). Thirty percent of patients, after a median time of 9 months from the start of second-line treatment, received a third-line treatment, mainly because of resistance (81%). As the best MR to third-line TKI, 50% of patients obtained a BCR::ABL1IS transcript level <1%. Overall, 9% of patients proceeded to stem-cell transplantation. Progression to blast phase occurred in 7% of patients, and all of them died. An additional patient died because of heart failure. The estimated 5-year progression-free survival and overall survival were 87% (95% CI, 67.1%-95.2%) and 83% (95% CI, 61.7%-93%), respectively. The MR at the last contact was ≥MR4 in 30% and MR3 in 22% of patients.
    CONCLUSION: Our analysis highlights that sequential treatment in patients with CP-CML resistant to frontline 2G-TKIs therapy is feasible and can be effective in a relevant proportion of patients.
    Keywords:  Chronic myeloid leukemia; Failure; Ponatinib; Sequential treatment; Tyrosine kinase inhibitors
    DOI:  https://doi.org/10.1016/j.clml.2026.07.011
  7. Blood Adv. 2026 Aug 20. pii: bloodadvances.2026020965. [Epub ahead of print]
    Second Line CD19 CAR-T vs Platinum Salvage and Autologous Stem Cell Transplant for Primary Mediastinal B-Cell Lymphoma.
    Xi Yang, Henry Dumke, Swetha Kambhampati Thiruvengadam, Christine Argao, Joseph G Schroers-Martin, Sree Lanka, Yazeed Sawalha, Hanan Alharthy, Sairah Ahmed, Izel Okcu, Grzegorz S Nowakowski, Peter G Doukas, Reem Karmali, Krithika Shanmugasundaram, Meryl Colton, Michael A Spinner, Stefania Marron Rodriguez, Adam S DuVall, Brock G Lakin, Christopher R D'Angelo, Vincenzo J Pizzuti, Manali Kamdar, Olutobi Adewale, Joanna M Rhodes, Yun Kyoung Ryu Tiger, Kelsey Baron, Allison M Bock, Marcus J Geer, Yasmin H Karimi.
      Primary mediastinal B-cell lymphoma (PMBCL) is a rare form of large B-cell lymphoma (LBCL) with around 90% of patients cured with frontline treatment. For relapsed or refractory (R/R) disease, the optimal treatment is unclear. CD19 chimeric antigen receptor-T cell (CAR-T) has been established as the preferred second line (2L) treatment for primary refractory or early relapsing LBCL based on the overall survival benefits observed in the landmark phase III trials. However, PMBCL patients were underrepresented on these pivotal studies. This study evaluated outcomes of 252 patients treated with 2L therapies for R/R PMBCL at 14 US institutions between 2001 and 2025. Platinum-based salvage with intent to proceed to high dose therapy and autologous stem cell transplant (HDT/ASCT) (platinum cohort) and CD19 CAR-T (CAR-T cohort) were given as 2L therapy in the real-world setting in 157 and 26 patients, respectively. Overall response rate (ORR), complete response (CR) rate and median progression-free survival (PFS) were significantly higher in the CAR-T cohort compared with the platinum cohort (ORR: 91.3% vs 44.2%, p <0.001; CR 65.2% vs 14.7%, p<0.001; median PFS not reached vs 3.5 months, hazard ratio (HR) 0.28, 95% CI 0.15-0.54, p=0.001). No significant difference was observed in overall survival. This study demonstrated superior response rate and PFS of CD19 CAR-T over platinum-based salvage with intent to proceed to HDT/ASCT as 2L treatment for R/R PMBCL.
    DOI:  https://doi.org/10.1182/bloodadvances.2026020965
  8. Blood. 2026 Aug 17. pii: blood.2025030170. [Epub ahead of print]
    Dual MYC and GSPT1 Protein Degrader for MYC-Driven Hematologic Malignancies.
    Yuki Nishida, Valeria Impedovo, Edward Ayoub, Natalia Baran, Darah A Scruggs, Hideaki Mizuno, Shayaun Khazaei, Lauren B Ostermann, Kazuharu Kamachi, Liang Zhang, Jo Ishizawa, Sandeep Singh, Andrea D Bedoy, Po Yee Mak, Bing Z Carter, Eiji Sugihara, Tetsuya Takimoto, Youzhi Tong, Honghua Yan, Dong Chen, Ji Huang, Hsu-Feng Chu, Liang Tong, Zamal Ahmed, Sarita Namjoshi, John Tainer, Mihai Gagea, Thomas Huynh, Abhishek Maiti, Koji Sasaki, Branko Cuglievan, Steffen Boettcher, Torsten Haferlach, Stefano Tiziani, Liandong Ma, Michael Andreeff.
      Direct targeting of the oncoprotein MYC has not yet been successful. We here report a novel dual protein degrader, GT19630, which binds directly to MYC and G1 to S phase transition protein 1 (GSPT1). GT19630 disrupts a novel feedforward loop of MYC and GSPT1, where MYC promotes transcription of GSPT1, and GSPT1 senses the stop codon of MYC to properly terminate its translation. The agent induces integrated stress response and abrogates oxidative phosphorylation through inhibition of the TCA cycle, resulting in apoptosis. GT19630 has superior activity compared to GSPT1- targeting molecular glues. GT19630 induces profound anti-proliferative effects and apoptosis at low nanomolar concentrations in a multitude of leukemia and lymphoma cell lines and primary samples, including those with TP53 mutations. GT19630 is highly active in vivo in models of therapy-resistant hematologic malignancies, including Burkitt's lymphoma, acute myeloid leukemia (AML) and multiple myeloma. CD34+ AML blasts overexpress MYC protein compared to normal hematopoietic stem/progenitor cells (HSPCs) and GT19630 induces greater cytotoxicity in AML cells compared to normal HSPCs. Further, GT19630 restores sensitivity to venetoclax and profoundly prolongs survival in vivo in venetoclax-resistant AML. GT19630 was well tolerated in humanized Crbn mice. In conclusion, our data support the development of the MYC/GSPT1 degrader GT19630 as a therapeutic strategy of MYC-driven hematologic malignancies.
    DOI:  https://doi.org/10.1182/blood.2025030170
  9. Blood Adv. 2026 Aug 20. pii: bloodadvances.2026020197. [Epub ahead of print]
    Richter transformation: emerging immunologic strategies beyond chemoimmunotherapy.
    Jian Li, Mark R Dowling, Constantine S Tam, Mary Ann Anderson, Philip A Thompson.
      Richter transformation (RT) is an aggressive lymphoma that arises in patients with chronic lymphocytic leukemia (CLL), most commonly diffuse large B-cell lymphoma (DLBCL-RT). Outcomes remain poor with conventional chemoimmunotherapy, reflecting the role of increased genomic instability and impaired DNA repair in the pathogenesis of RT.. Targeted therapies used in CLL (BTK or BCL2 inhibition) have shown efficacy in RT; however, durable disease control remains elusive, highlighting the need for immunological approaches. This review discusses the clinical evidence supporting immunologic approaches in RT, focusing on allogeneic stem cell transplantation, chimeric antigen T-cell (CAR T-cell) therapy, bispecific T-cell directing antibodies, and checkpoint inhibition. Allogeneic stem cell transplantation can provide long-term remission in selected patients; however, there are considerable barriers, such as the requirement for adequate patient fitness and pre-transplant disease control. Post-approval observational studies have provided evidence of the efficacy and safety of CAR T-cell therapy, as well as the risk of immunologic toxicity. Early phase studies on bispecific antibodies and checkpoint inhibition have demonstrated disease activity, and multiple studies on combination strategies are ongoing. Future priorities include optimizing disease control prior to immunologic therapy, testing novel combination approaches and conducting correlative studies to optimize future therapeutic strategies.
    DOI:  https://doi.org/10.1182/bloodadvances.2026020197
  10. Blood. 2026 Aug 20. 148(8): 923-924
    A tale of networking glycoproteins.
    Renhao Li.
      
    DOI:  https://doi.org/10.1182/blood.2026034977
  11. Blood. 2026 Aug 18. pii: blood.2025032682. [Epub ahead of print]
    Eltrombopag plus cyclosporine A for moderate aplastic anemia (EMAA): a placebo-controlled, double-blind, phase 3 trial.
    Britta Höchsmann, Philippe Schafhausen, Fabian Beier, Michael Heuser, Jörg Westermann, Beatrice Drexler, Alexander Röth, Regina Theresia Herbst, Mathias Hänel, Michaela Schwarz, Flore Sicre de Fontbrune, Regis Peffault de Latour, Astrid Marx-Hofmann, Antonia Beitzen-Heineke, Jens P Panse, Felicitas R Thol, Sixten Körper, Tim H Brümmendorf, Hubert Schrezenmeier.
      Eltrombopag combined with horse antithymocyte globulin and cyclosporine A (CSA) is the standard of care for patients with severe aplastic anemia who are not eligible for stem cell transplantation. No consensus exists on the optimal treatment of moderate aplastic anemia (MAA). The "Eltrombopag for MAA" (EMAA) trial is an investigator-initiated, prospective, randomized, placebo-controlled, double-blind, multicenter, phase III trial and compared eltrombopag+CSA (n=41) with placebo+CSA (n=44) as a first-line therapy for MAA patients with clinically significant cytopenia. In patients with evaluable response at week 24 (n=75), the overall response rate (ORR), including partial response (PR) and complete response (CR), was significantly higher in the eltrombopag+CSA arm (71.4%; 95% confidence interval [CI], 54.8%-83.8%) than in the placebo+CSA arm (42.5%; 95% CI, 28.5%-57.8%) (p=0.011, Fisher's exact test; primary endpoint). After response assessment at week 24 and unblinding, patients in the placebo arm without CR were switched to receive eltrombopag in addition to continued CSA. This group achieved an ORR of 73.5% by week 48 (p=0.009, McNemar test, comparing response at 24 vs. 48 weeks). Relapse rate and failure-free survival did not differ significantly among the arms. Eltrombopag was well tolerated without new safety concerns. Adding eltrombopag to CSA for first-line treatment of MAA significantly improves trilineage hematologic response at week 24 and addition of eltrombopag in patients without CR after 24 weeks of single-agent CSA treatment also significantly improves the ORR. The trial was registered at www.clinicaltrials.gov as #NCT02773225 and at European Union Drug Regulating Authorities Clincial Trials as EudraCT2014-000174-19.
    DOI:  https://doi.org/10.1182/blood.2025032682
  12. Front Oncol. 2026 ;16 1897942
    Ferroptosis in multiple myeloma: molecular mechanisms and therapeutic opportunities.
    Wanfu Jiang, Li Xu, Changling Zhu, Guangqiang Bai, Sihao Peng, Na Ma.
      Multiple myeloma (MM) is a hematologic malignancy driven by clonal plasma-cell proliferation and remains largely incurable owing to disease relapse and acquired drug resistance. Ferroptosis, an iron-dependent form of regulated cell death characterized by excessive lipid peroxidation, has emerged as a potential therapeutic target in cancer and is increasingly implicated in MM biology. Unlike apoptosis and other classical cell death pathways, ferroptosis is closely associated with dysregulated iron metabolism, oxidative stress, and lipid peroxidation, all of which are key features of MM biology. This review first outlines the molecular mechanisms of ferroptosis and then summarizes current evidence linking ferroptosis to MM progression, therapeutic resistance, and emerging therapeutic strategies. In addition, current therapeutic strategies targeting ferroptosis are discussed, including inhibition of system Xc-, direct targeting of GPX4, modulation of iron metabolism, and their potential synergistic effects with existing anti-myeloma therapies. Finally, the major challenges associated with clinical translation are highlighted, together with future directions for biomarker development and ferroptosis-based therapeutic strategies. Collectively, ferroptosis represents a promising therapeutic concept for exploiting redox and metabolic vulnerabilities in MM. Nevertheless, current knowledge is derived predominantly from preclinical studies, and successful clinical translation will require improved tumor selectivity, rigorous safety evaluation, and biomarker-guided patient stratification.
    Keywords:  GPX4; SLC7A11; drug resistance; ferroptosis; iron metabolism; lipid peroxidation; multiple myeloma; therapeutic target
    DOI:  https://doi.org/10.3389/fonc.2026.1897942
  13. Haematologica. 2026 Aug 20.
    Tripping the switch: p38 inhibition unlocks venetoclax and inotuzumab ozogamicin synergy.
    Alisson Charmey, Beat C Bornhauser.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2026.301601
  14. Br J Haematol. 2026 Aug 17.
    Real-world outcomes of venetoclax plus hypomethylating agents in unfit acute myeloid leukaemia: Results of the GIMEMA AML2320 trial.
    Raffaele Palmieri, Alfonso Piciocchi, Stefano Soddu, Marco Frigeni, Erika Borlenghi, Nicola Fracchiolla, Maria Paola Martelli, Ernesta Audisio, Alessandro Cignetti, Giacomo Gianfaldoni, Calogero Vetro, Nicola di Rienzo, Daniela Esposito, Ambra Di Veroli, Carmine Selleri, Federica Gigli, Antonio Curti, Antonino Mulè, Catello Califano, Sara Bigliardi, Massimo Breccia, Claudio Fozza, Monica Bocchia, Albana Lico, Federico Simonetti, Elisabetta Pierdomenico, Monia Marchetti, Ilaria Cerroni, Francesco Buccisano, Maria Ilaria Del Principe, Luca Maurillo, Giovangiacinto Paterno, Paola Fazi, Marco Vignetti, Giuseppe Rossi, Alessandro Rambaldi, Adriano Venditti.
      Venetoclax (VEN) plus hypomethylating agents (HMAs) represents the standard of care for newly diagnosed acute myeloid leukaemia (AML) patients unfit for intensive chemotherapy, but prospective real-world observational data outside randomized clinical trials remain limited. The Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) AML2320 is a prospective, multicentre, observational study (NCT04589728) including 193 newly diagnosed unfit AML patients receiving VEN plus azacitidine or decitabine between November 2020 and December 2021. Primary end-point was overall survival (OS); secondary end-points included composite complete remission (cCR), disease-free survival and safety. Median age was 74 years with 42% of patients being ≥75 years. After completing cycle 4, cCR was achieved in 73% of the patients, with 54% responding before cycle 2. After a median follow-up of 23 months, median OS was 13.0 months. cCR achievement within cycle 4 correlated with longer OS (19.1 vs. 9.1 months, p = 0.001). Patients receiving 400 mg VEN without azoles had improved OS compared with those on reduced doses with azoles (18.2 vs. 11.4 months, p = 0.015). An anchored matching-adjusted indirect comparison with the phase III VIALE-A trial (NCT02993523) showed comparable median OS (14.8 months vs. 14.9 months; p = 0.6). The GIMEMA AML2320 trial confirmed the efficacy of VEN/HMAs in a prospective, real-world unfit population. Early remission was associated with improved outcomes.
    Keywords:  acute myeloid leukaemia; hypomethylating agents; real‐world evidence; unfit patients; venetoclax
    DOI:  https://doi.org/10.1111/bjh.70752
  15. Br J Pharmacol. 2026 Aug 16.
    Histone deacetylase inhibitors as venetoclax-sensitising partners in acute myeloid leukaemia: Mechanisms, pharmacology and translational perspectives.
    Jaebok Lee, Marc Diederich.
      Venetoclax combined with hypomethylating agents has improved treatment for older or unfit patients with acute myeloid leukaemia (AML), but resistance and relapse remain common. This review analyses the rationale for combining venetoclax with inhibitors of histone deacetylase (HDAC). Class I histone deacetylase 1/2/3-dependent suppression of myeloid cell leukaemia 1 and de-repression of pro-apoptotic BCL-2 homology domain 3 (BH3)-only genes provide the strongest mechanistic basis, whereas HDAC6/heat shock protein 90, autophagy, immune-modulatory and super-enhancer mechanisms remain context-dependent and incompletely validated in primary AML under venetoclax exposure. Effects of HDAC inhibition must also be interpreted in the context of tumour protein 53 status. Early HDAC inhibitor-containing composite regimens, particularly chidamide-based CACAG-VEN (chidamide, venetoclax, azacitidine, low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor), report high response rates, including overall response rate of 76.5-98.0%, complete remission/complete remission with incomplete count recovery or composite complete remission of 73.5-93.3%, and measurable residual disease negativity of 44-61%. This six-component regimen does not isolate the contribution of HDAC inhibition. Future development should prioritise biomarker-selected trials that hold non-HDAC components constant, incorporate pharmacodynamic HDAC engagement and BH3 profiling, and account for cytochrome P450 3A-mediated drug interactions. HDAC inhibitor-venetoclax combinations are mechanistically rational, but standard-of-care positioning requires randomised or pharmacodynamic validation.
    Keywords:  acute myeloid leukaemia; combination therapy; drug resistance; histone deacetylase inhibitor; venetoclax
    DOI:  https://doi.org/10.1111/bph.70641
  16. Br J Haematol. 2026 Aug 21.
    BrECADD in three days: Implementation of a condensed intensive first-line regimen in Hodgkin lymphoma.
    Christian Peter Jaworek, Maja Supprian, Paul Jan Bröckelmann, Hishan Tharmaseelan, Justin Ferdinandus, Dennis A Eichenauer, Anne Sophie Robertz, Janina Jablonski, Vincent Combüchen, Jan-Oliver Staak, Karin Töpelt, Jan-Michel Heger, Jon Rischewski, Jannik Stemler, Wolfram Klapper, Peter Borchmann, Bastian von Tresckow.
      Intensive multiagent treatment regimens have substantially improved outcomes in advanced-stage classic Hodgkin lymphoma (cHL). Brentuximab vedotin (BV), etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (BrECADD) demonstrated the highest efficacy in cHL reported to date in a randomised phase III trial. Cytotoxic agents are conventionally administered during the first 4 days of a 21-day cycle. A total of four cycles are applied to patients with a complete response after two cycles, otherwise six cycles. We developed a condensed BrECADD protocol, reducing intravenous administration days to only three (-25%). Between January 2024 and July 2026, 30 patients received 132 cycles of 3-day BrECADD at our institution. Primary objective was to describe feasibility and safety; secondary objectives included response, progression-free survival (PFS) and overall survival (OS). Grade ≥3 adverse events occurred in 23 patients (77%), predominantly haematological. Six patients (20%) had grade ≥3 infections (four viral, two bacterial) and six (20%) had pathogen-unspecified febrile neutropenia. Twenty-four patients (80%) required only four BrECADD cycles. There were no treatment discontinuations. After a median follow-up of 18 months (range 4-29), 1-year PFS and OS rates were both 100%. Based on these encouraging results, the condensed 3-day protocol is considered feasible and we recommend it for future BrECADD use.
    Keywords:  BrECADD; Hodgkin lymphoma; brentuximab vedotin; first‐line treatment
    DOI:  https://doi.org/10.1111/bjh.70771
  17. Blood. 2026 Aug 17. pii: blood.2026033773. [Epub ahead of print]
    Blood-based MALDI-TOF mass spectrometry versus bone marrow MRD for monitoring multiple myeloma: CASSIOPEIA study results.
    Thomas Dejoie, Neila Rebouh, Jill Corre, Soraya Wuilleme, Françoise Kraeber-Bodere, Cyrille Hulin, Aurore Perrot, Cyrille Touzeau, Xavier P Leleu, Bertrand Arnulf, Lionel Karlin, Philippe Moreau, Helene Caillon.
      Minimal residual disease (MRD) status is widely used to assess depth of response and predict outcome in multiple myeloma, but bone marrow MRD testing is invasive and subject to sampling variability. Blood-based mass spectrometry (MS), which measures patient-specific monoclonal immunoglobulins, offers a non-invasive approach to monitoring residual disease. Using the structured assessment schedule of the CASSIOPEIA trial, we compared serum MS with bone marrow MRD by next-generation flow cytometry (NGF) and next-generation sequencing (NGS). This retrospective post-hoc analysis included 237 patients from the CASSIOPET companion study with paired serum and bone marrow samples prospectively collected at predefined CASSIOPEIA time points from post-induction through maintenance. MRD results by MS, NGF, and NGS were evaluated for associations with progression-free survival, agreement between methods, longitudinal changes, and sustained MRD status according to International Myeloma Working Group criteria. At all time points, MRD negativity by any method was associated with longer progression-free survival, with comparable landmark prognostic performance across platforms. Agreement between serum MS and bone marrow MRD improved during maintenance, with high positive predictive value and high negative predictive value relative to a 10⁻⁵ marrow reference, but more limited rule-out performance against NGS at 10⁻⁶. Sustained MRD negativity over 1 and 2 years identified patients with favorable outcomes irrespective of method. These findings support a complementary, phase-adapted role for serum MS alongside bone marrow MRD testing, enabling frequent non-invasive monitoring during maintenance while preserving bone marrow assessment when maximum sensitivity is required. The Cassiopeia trial is registered at www.clinicaltrials.gov as NCT02541383.
    DOI:  https://doi.org/10.1182/blood.2026033773
  18. Haematologica. 2026 Aug 20.
    Making remissions last: the promise of maintenance in primary central nervous system lymphoma.
    Christian Grommes, Lauren R Schaff.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2026.301604
  19. Blood Adv. 2026 Aug 21. pii: bloodadvances.2026021739. [Epub ahead of print]
    Fracturing ferric carboxymaltose from the iron pharmacopeia.
    Daniel Wang, Sam Hirniak, Adam Cuker, George Goshua.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2026021739
  20. Case Rep Oncol. 2026 Jan-Dec;19(1):19(1): 1268-1274
    Weekly Metronomic Venetoclax and Decitabine/Cedazuridine in Acute Myeloid Leukemia Patient Declining Blood Transfusion.
    Mahmood Aldapt, Talha Badar, Antoine N Saliba, James Foran, Sidney Bianco, Catherine Hanratty, Hemant Murthy.
       Introduction: Acute myeloid leukemia (AML) treatment typically involves intensive chemotherapy associated with prolonged cytopenias and frequent transfusion requirements. Patients who decline blood products, such as Jehovah's Witnesses (JW), present a therapeutic challenge, as transfusion support is integral to standard care. Emerging low-intensity regimens combining venetoclax (VEN) with hypomethylating agents offer a potential alternative with reduced myelosuppression.
    Case Presentation: A 77-year-old male JW with AML with myelodysplastic syndrome-related changes and mutations in DDX41, ASXL1, and PPM1D presented with pancytopenia. Due to refusal of transfusions, he was treated with a metronomic, all-oral regimen of VEN 400 mg weekly and decitabine/cedazuridine (DEC-C) 35/100 mg weekly, supported by erythropoiesis-stimulating agent (darbepoetin alfa) and thrombopoietin agonist (romiplostim) as needed. After 4 weeks, bone marrow blasts decreased from 20-25% to 10%, with clearance of ASXL1 and PPM1D mutations and reduction of DDX41 variant allele frequency (VAF) to 2.9% from 9.7%. At 26 weeks, marrow blasts further decreased to 5%, DDX41 VAF remained low (2.6%), and counts normalized (ANC 1.73 × 103/µL, hemoglobin 13.1 g/dL, PLT 256 × 103/µL) without any transfusions.
    Conclusion: This case demonstrates that a metronomic, all-oral VEN and DEC-C regimen can achieve hematologic improvement and molecular response in AML while maintaining transfusion independence. It highlights a feasible and safe therapeutic option for patients declining blood products, achieving disease control with minimal toxicity.
    Keywords:  Acute myeloid leukemia; Case report; Decitabine/cedazuridine; Jehovah’s Witness; Metronomic; Venetoclax
    DOI:  https://doi.org/10.1159/000551645
  21. Br J Haematol. 2026 Aug 18.
    Danburstotug, an anti-PD-L1 antibody, in relapsed/refractory extra-nodal natural killer/T-cell lymphoma: The phase 2 DISTINKT study.
    Won Seog Kim, Seok Jin Kim, Jae-Cheol Jo, Sang Eun Yoon, Youngil Koh, Deok-Hwan Yang, Dok Hyun Yoon, Junhun Cho, Sung Young Lee, Suyeon Kim, Seongyeon Kang, Woochan Hwang, Hyukjung Kim, Hwi-Yeol Yun, Jihyun Jeon, Chul Ahn, Heung Tae Kim.
      Relapsed/refractory extra-nodal natural killer/T-cell lymphoma (R/R ENKTL) has limited treatment options. Danburstotug, an antibody targeting programmed death-ligand 1 (PD-L1), was evaluated in adults with R/R ENKTL in a phase 2, open-label study (NCT04414163). Danburstotug 20 mg/kg was administered intravenously every 2 weeks up to 52 cycles, disease progression or unacceptable toxicity. In the full analysis set (n = 19), objective response rate (ORR; primary end-point) was 78.9% (95% confidence interval 54.4-94.0); complete response (CR) rate was 63.2% (38.4-83.7); 76.9% of participants maintained responses; and 90.9% of participants maintained CR for 2 years. In the intention-to-treat population (n = 23), median progression-free survival (PFS) was 29.4 months (12.0-46.9; 2-year PFS rate 62.1%); and median overall survival was 40.2 months (25.1-55.4; 2-year overall survival rate 77.9%). Treatment-emergent adverse events occurred in 91.3% of 23 participants (73/83 events were grade 1/2); grade 3 serious treatment-related adverse events comprised liver injury and uveitis (one participant each). High PD-L1 membrane specificity (MS) was associated with greater ORR, CR rate and PFS versus low PD-L1 MS. In tumour immune microenvironment assessments, clinical benefit was observed across immune tolerance and immune evasion subtypes, despite lower PD-L1 expression in immune evasion-B. Danburstotug demonstrated robust, durable efficacy and manageable safety. PD-L1 MS showed potential as a predictive biomarker.
    Keywords:  anti‐PD‐L1 antibody; clinical trial; danburstotug; extra‐nodal natural killer/T‐cell lymphoma; immunotherapy; relapsed and refractory
    DOI:  https://doi.org/10.1111/bjh.70742
  22. EJHaem. 2026 Apr;7(2): e70213
    Chronic Myeloid Leukemia Presenting With T-Lymphoid Blast Crisis in a Young Female With Marked Hyperleukocytosis: A Case Report.
    E Somasundaram, R P Hasserjian, B J Aubrey, A T Fathi, H Hock.
       Background: Chronic myeloid leukemia (CML) presenting in blast crisis (BC) is uncommon in the era of tyrosine kinase inhibitor (TKI) treatment, and T-lymphoblastic BC is exceptionally rare. We report a case of T-lymphoid BC presenting with extreme hyperleukocytosis.
    Case: A 37-year-old woman with previously diagnosed chronic phase CML who had declined therapy presented with dyspnea and constitutional symptoms. She was found to have diffuse lymphadenopathy and a markedly elevated white cell count (WCC) of 729 × 109/L with 24% blasts. Bone marrow biopsy showed T-lymphoblastic leukemia, BCR::ABL1 fusion (p210), and a RUNX1 gene mutation as well as an IKZF1 gene mutation. Staging revealed extensive nodal, splenic, renal, and ocular involvement. She underwent cytoreduction with hydroxyurea, prednisone, and dasatinib, followed by HyperCVAD induction. She achieved complete remission and proceeded to a sibling-donor allogeneic stem cell transplant. A bone marrow biopsy 100 days after transplant showed complete remission without MRD assessed by PCR and flow cytometry. At 6 months post-transplant, she remains disease-free.
    Discussion: T-lymphoid BC in CML is exceedingly rare, with limited knowledge of disease characteristics, molecular features, prognosis, and treatment outcomes. This case highlights the importance of early recognition, comprehensive molecular workup, and aggressive therapy. Despite historically poor outcomes, aggressive induction with BCR-ABL1 kinase inhibition followed by transplant may offer durable disease control.
    Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.
    Keywords:  CML; T cell; blast crisis; hyperleukocytosis
    DOI:  https://doi.org/10.1002/jha2.70213
  23. Cell Biochem Funct. 2026 Aug;44(8): e70286
    Drug Resistance in Multiple Myeloma: Tumor-Intrinsic Mechanisms and the Bone Marrow Microenvironment.
    Yixuan Chen, Wenming Huang, Mingxuan Tang, Xiaotao Wang.
      Multiple myeloma (MM) is a malignant plasma cell disorder, and despite substantial improvements in prognosis achieved through chemotherapy, immunotherapy, and autologous stem cell transplantation, most patients ultimately develop relapsed or refractory disease. Drug resistance (DR) is increasingly recognized as a dynamically evolving ecosystem shaped by tumor-intrinsic plasticity and continuous remodeling of the bone marrow microenvironment (BMME), rather than as a single molecular lesion. This review summarizes the major mechanisms of resistance across key drug classes, including alterations in drug targets and signaling nodes, rewiring of apoptotic, proteostatic, and metabolic circuits, and BMME-dependent protection. We highlight how these processes converge on a limited set of survival hubs and collectively raise the apoptotic threshold under therapeutic pressure. The key to overcoming DR is to conceptualize it as an evolving ecosystem, thereby enabling rational, mechanism-based combination and sequencing strategies that may prolong progression-free survival and move MM closer to a functional cure.
    Keywords:  bone marrow microenvironment; cell communication; drug resistance; immunotherapy; multiple myeloma; signal transduction
    DOI:  https://doi.org/10.1002/cbf.70286
  24. bioRxiv. 2026 Aug 07. pii: 2026.08.06.743109. [Epub ahead of print]
    Stability of c-Myc protein differentiates Ras oncogene addiction and MAPK pathway dependency in Ras-mutant multiple myeloma.
    Yeon-Hwa Lee, Christophe Cataisson, Haibo Zhang, Snehal Gaikwad, Wendy D du Bois, Aleksandra M Michalowski, Howard H Yang, Thomas J Meyer, Ryan M Young, Beverly A Mock, Ji Luo.
      Multiple myeloma (MM) is a plasma cell malignancy that frequently harbors activating mutations in NRAS and KRAS oncogenes. Previous clinical trials targeting the Ras/MAPK oncogenic pathway with MEK inhibitors (MEKi) were met with limited efficacy, and newer generation of Ras inhibitors (RASi) have not been specifically evaluated in MM patients. To investigate the vulnerabilities of Ras-mutant MM to targeted therapies, we examined the sensitivity of a panel of human MM cell lines to the RASi RMC-6236 (daraxonrasib) and the MEKi trametinib. Although Ras-mutant MM cells are responsive to oncogenic Ras signaling and are sensitive to RAS inhibition, their sensitivity to MEK inhibition is heterogeneous. Mechanistic studies revealed that c-Myc protein is destabilized by MEK inhibition only in MEKi-sensitive MM cells but not in MEKi-resistant cells, and pharmacological and genetic stabilization of c-Myc is sufficient to confer MEKi resistance. In contrast, Ras inhibition reduced c-Myc protein across all MM cell lines tested, regardless of their dependency on the MAPK pathway, and c-Myc expression was insufficient to promote RASi resistance. Together, these findings demonstrate that c-Myc protein stability differentiates the response of Ras-mutant MM cells to Ras and MEK inhibition, and suggest that direct targeting of the Ras oncoprotein, rather than its downstream MAPK pathway, may present a more effective strategy.
    DOI:  https://doi.org/10.64898/2026.08.06.743109
  25. Hematol Oncol. 2026 Sep;44(5): e70223
    Venetoclax in Combination With Chemo-Immunotherapy in Richter Transformation: A Real-Life Experience.
    L Ballotta, J Olivieri, D Facchinelli, I Ferrarini, A Visentin, R Moia, M Cavallari, V Innao, E Derenzini, P M Nierychlewska, A Cuda, V Gattei, M Ballerini, E Lucchini, M Turoldo, M C Rossetti, F Gaudio, F Zaja.
      The prognosis of Richter Transformation (RT) with standard chemo-immunotherapy (CIT) remains poor. Several previous experiences with Venetoclax (V) in combination with CIT demonstrated the feasibility and safety of V-CIT based regimens in RT. This is a retrospective, observational multicenter study aimed to assess the efficacy and safety of the real-life use of V-CIT in the treatment of RT. Response assessments were evaluated according to the Lugano 2014 criteria. 20 consecutive patients treated with V-CIT based regimens from October 2018 to July 2024, were included. Median age was 63.5 years (33-73), with 75% of males. 11/17 were IGHV unmutated and 8/18 carried a mutation for Tp53 and/or a del17p. The median time from CLL diagnosis to RT was 6.5 years (0-17). A clonal relationship was demonstrated in 16/16 evaluable patients. The median number of prior treatments for CLL was 2 (0-4): CIT in 10, BTKi in 10, V based treatment in 4, no previous therapy in 5. V was associated with R-DA-EPOCH, R-CHOP, and BFM in 10, 9 and 1 patients for a median number of 4 cycles (1-6). ORR was 55% with 10 CR (50%) and 1 PR (5%). 3 patients had progressive disease (PD) and 1 died for multiorgan failure. 7 patients received allogeneic-HSCT consolidation. At a median follow up of 11.5 months (1-78), 10 patients, including 5 who received HSCT, are alive in CR; median PFS and OS were not reached. All patients experienced grade 3-4 hematological toxicities: neutropenia (100%), anemia (50%) and thrombocytopenia (25%). Non-hematological toxicities included: febrile neutropenia (15%), covid19 (25%), other infections (30%), nausea (10%), thrombotic/hemorrhagic events (10%). Data from this real-life experience confirm the feasibility and the activity of V-CIT based combination in younger fit RT patients, where the high rate of initial response may allow a significant proportion to receive allogeneic-HSCT consolidation. New studies with V combinations are ongoing and the comparison with this real-life data may be worthwhile to better understand their therapeutic impact.
    DOI:  https://doi.org/10.1002/hon.70223
  26. Blood Adv. 2026 Aug 19. pii: bloodadvances.2026021269. [Epub ahead of print]
    American Society of Hematology 2026 Guidelines for Immune Thrombocytopenia (ITP): Initial and Second-Line Therapy in Adults with Primary ITP.
    Adam Cuker, Deirdra R Terrell, Honieh Sowdagar, Donald M Arnold, Sylvain Audia, James B Bussel, Tomas Jose Gonzalez-Lopez, Rachael F Grace, Camila Masias, Keith R McCrae, Mirjana Mitrovic, Cindy E Neunert, Sandhya Ramanathan Panch, Surbhi Shah, Brenda G Shy, Jessica VandeVelde, Douglas B Cines, Sara K Vesely.
       BACKGROUND: Since publication of the American Society of Hematology 2019 Guidelines for Immune Thrombocytopenia (ITP), new clinical trials have been completed and new treatments have become available.
    OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) are a focused update of the 2019 ASH ITP guidelines, centering on treatment of adults with primary ITP.
    METHODS: ASH formed a multidisciplinary guideline panel including two patient representatives that was balanced to minimize potential bias from conflicts of interest. The University of Oklahoma supported the guideline development process, including updating or performing systematic evidence reviews (up to July 19, 2025). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and identification of areas with new data or where application of new methods would be of benefit. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks and the GRADE framework for multiple comparisons, to assess evidence and make recommendations, which were subject to public comment.
    RESULTS: The panel agreed on recommendations in adults with primary ITP regarding initial therapy and second-line treatment in patients who failed first-line corticosteroids. The panel also issued good practice statements on thrombopoietic agent switching and splenectomy.
    CONCLUSIONS: Novel recommendations of these guidelines include: (1) initial therapy with a combination of rituximab plus corticosteroids or a thrombopoietic agent plus corticosteroids rather than corticosteroids alone (conditional recommendation) and (2) a thrombopoietic agent (strong recommendation) or rituximab (conditional recommendation) for patients who failed first-line corticosteroids.
    DOI:  https://doi.org/10.1182/bloodadvances.2026021269
  27. Blood. 2026 Aug 11. pii: blood.2026033305. [Epub ahead of print]
    NRAS knockdown reverses monocytic cell state and resensitizes resistant FLT3-AML cells to gilteritinib.
    Sunil K Joshi, Hadi Maazi, Janét Pittsenbarger, Belinda B Garana, Andy Kaempf, Ariane Huang, Marina A Gritsenko, Chelsea Hutchinson-Bunch, Karl K Weitz, Rosalie K Chu, Sara J C Gosline, Paul D Piehowski, Ann-Kathrin Eisfeld, Martin P Carroll, Alexander E Perl, Karin D Rodland, Bill H Chang, Alexey S Revenko, Jeffrey W Tyner, Brian J Druker, Elie Traer.
      While the FLT3 inhibitor gilteritinib is initially effective in patients with FLT3-mutated acute myeloid leukemia (AML), patients invariably relapse within months of treatment. Gilteritinib resistance is commonly driven by the emergence of NRAS mutations and a shift towards a more monocytic cell state. We hypothesized that directly targeting and depleting NRAS protein would reverse these adaptive differentiation changes and restore therapeutic sensitivity. To test this, we utilized a mutation-agnostic antisense oligonucleotide (ASO) to selectively knock down NRAS expression across gilteritinib-resistant AML cell lines, in vivo cell-line-derived xenografts, and primary patient samples. NRAS ASO successfully resensitized gilteritinib resistant cells with multiple distinct NRAS mutations, displaying superior efficacy compared to downstream MEK inhibition. This therapeutic efficacy was independent of NRAS mutant variant allele frequency, suggesting that wild-type NRAS may also contribute to resistance. Comprehensive multi-omic profiling (transcriptomics, proteomics, phosphoproteomics) revealed that NRAS knockdown consistently reversed monocytic phenotype, shifting cells back toward a more primitive cell state. Monocytic differentiation and NRAS mutations are established drivers of resistance to diverse targeted regimens in AML, including FLT3, IDH, and BCL2 inhibitors, so we also tested venetoclax resistant primary cells with NRAS mutations. Resistant cells were resensitized to venetoclax after NRAS knockdown, suggesting that NRAS knockdown may be more broadly applicable in overcoming monocytic cell state and drug resistance in AML.
    DOI:  https://doi.org/10.1182/blood.2026033305
  28. Am J Hematol. 2026 Aug 19.
    Hypomethylating Therapy in VEXAS Syndrome: Disease Modification Beyond Bridging to Transplant.
    Emanuele Ammatuna.
      
    DOI:  https://doi.org/10.1002/ajh.70478
  29. Ther Adv Hematol. 2026 ;17 20406207261474934
    Novel targeted therapies for central nervous system involvement in chronic lymphocytic leukemia: A systematic review.
    Abdulrahman F Al-Mashdali, Mujahid O Abdelraof, Raga M Mukhtar, Shehab F Mohamed.
       Background: Central nervous system (CNS) involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare, diagnostically challenging, and historically associated with poor outcomes. Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL2) inhibitors may improve outcomes, but evidence remains limited to case reports and small series.
    Objectives: To summarize the clinical features, diagnostic findings, treatment patterns, efficacy, safety, and outcomes of CNS involvement by CLL/SLL treated with novel targeted therapies.
    Design: Systematic review of published case reports, case series, and cohorts with extractable individual-level data.
    Methods: PubMed, Scopus, and Web of Science were searched from database inception to September 15, 2025. Eligible studies reported adults with CNS involvement by CLL/SLL treated with targeted agents, including BTK inhibitors, venetoclax, duvelisib, dasatinib, or other novel therapies. Chemotherapy-only regimens and Richter transformation cases were excluded. Patient-level data were extracted, and study quality was assessed using the Murad tool.
    Results: Twenty-six studies including 32 patients were analyzed. Median age at CNS presentation was 65.5 years, and most cases occurred at relapse. CNS disease was meningeal in 47%, parenchymal in 22%, and combined in 31%. Adverse biological features, including TP53 mutation, del(17p), and unmutated immunoglobulin heavy chain variable region (IGHV), were common. Across 34 treatment regimens, the overall response rate was 94.1%, with 55.9% complete and 38.2% partial responses. Ibrutinib was the most frequently used agent, while venetoclax and ibrutinib-venetoclax showed favorable activity. Other targeted agents showed promising responses in isolated cases. Toxicities were infrequent and consistent with known safety profiles.
    Conclusion: BTK inhibitor- and venetoclax-based regimens show encouraging activity in CNS involvement by CLL/SLL, including in genomically adverse disease. However, the current evidence remains primarily exploratory and descriptive. Prospective multicenter studies are warranted to establish optimal treatment sequencing, combination strategies, and the role of adjunctive intrathecal therapy or radiotherapy.
    Keywords:  BTK inhibitors; central nervous system; chronic lymphocytic leukemia; ibrutinib; small lymphocytic lymphoma; targeted therapy; venetoclax
    DOI:  https://doi.org/10.1177/20406207261474934
This page is being maintained by Thomas Krichel. It was last updated on 2026‒08‒23 at 17:39.