bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–04–05
twenty-two papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Evolution of the European LeukemiaNet recommendations for chronic myeloid leukemia.
  2. [Hematologic responses with favorable safety in three elderly patients with polycythemia vera treated with ropeginterferon alfa-2b].
  3. Venetoclax in myeloma: t(11;14) and what else?
  4. Breaking new ground with antibody-drug conjugates in myeloma.
  5. [Sustained hematologic complete response after discontinuation of ropeginterferon alfa-2b in patients with polycythemia vera].
  6. [Sustained molecular response after discontinuation of ropeginterferon alfa-2b in a young patient with polycythemia vera].
  7. Neutrophil-to-lymphocyte ratio half reduction as a surrogate of molecular response in polycythemia vera treated with ropeginterferon alfa-2b.
  8. Lenalidomide plus rituximab for previously untreated advanced follicular lymphoma: the 10-year RELEVANCE trial analysis.
  9. Relapsed classic Hodgkin lymphoma; should all patients receive an autologous stem cell transplant? - the PRO.
  10. Turning off SP140 to turn on HSCs.
  11. BCR::ABL1 tyrosine kinase inhibitors induce ribosome collisions to activate ZAK-dependent ribotoxic stress and apoptosis in chronic myeloid leukemia.
  12. A different alternative to warfarin?
  13. Final phase 2 study results of acalabrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia.
  14. BCMA/CD19 dual-targeting CAR T cell therapy in older patients with newly diagnosed multiple myeloma: a phase I study.
  15. Refining prognostic tools in Waldenström macroglobulinemia.
  16. Hypomethylating agents plus venetoclax in younger acute myeloid leukemia: Meta-analysis of a shifting treatment paradigm.
  17. Azacitidine for MDS and CMML.
  18. Precision targeting of CD38 in immune thrombocytopenia: Mechanistic foundations and therapeutic implications.
  19. Zanubrutinib-rituximab followed by shortened chemoimmunotherapy as frontline treatment for mantle cell lymphoma (CHESS): a phase II trial.
  20. Single-cell technologies in deciphering drug resistance of multiple myeloma: mechanistic insights and clinical translation prospects.
  21. Primary sinonasal DLBCL: High prevalence of MCD subtype and CNS risk.
  22. Arginine deprivation induces ROS dependent autophagic cell death in human acute myeloid leukemia cells.
  1. Expert Rev Hematol. 2026 Apr 01.
    Evolution of the European LeukemiaNet recommendations for chronic myeloid leukemia.
    Alkim Yolcu, Ibrahim Celalettin Haznedaroglu.
       INTRODUCTION: Chronic myeloid leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), leading to near-normal life expectancy for most patients diagnosed in the chronic phase. The European LeukemiaNet (ELN) recommendations provide the internationally recognized framework for the diagnosis, monitoring, and treatment of CML.
    AREAS COVERED: This review provides a chronological overview of the evolution of ELN recommendations for CML across five updates (2006, 2009, 2013, 2020, and 2025). Relevant literature published up to January 2026 was identified through a search of PubMed/MEDLINE, using keywords including 'chronic myeloid leukemia,' 'CML,' 'European LeukemiaNet,' 'ELN recommendations,' 'tyrosine kinase inhibitors,' and 'treatment-free remission.'
    EXPERT OPINION: Over time, ELN recommendations have shifted from cytogenetic to molecular monitoring, incorporated second-generation TKIs, and introduced treatment-free remission as a major therapeutic goal. The latest framework emphasizes personalized CML management by integrating molecular response with patient-specific factors, reflecting the broader evolution of precision medicine in hematology.
    Keywords:  CML; Chronic myeloid leukemia; ELN recommendations; European LeukemiaNet; molecular response; personalized medicine; treatment-free remission; tyrosine kinase inhibitors
    DOI:  https://doi.org/10.1080/17474086.2026.2654720
  2. Rinsho Ketsueki. 2026 ;67(3): 214-219
    [Hematologic responses with favorable safety in three elderly patients with polycythemia vera treated with ropeginterferon alfa-2b].
    Satoko Oka, Yuina Ueda, Takaya Mitsuyoshi, Kazuo Ono.
      Treatment selection for patients with polycythemia vera (PV) is based on patient age and history of thrombosis. The standard treatment is low-dose aspirin and phlebotomy, with cytoreductive therapy added for high-risk PV. Clinical trials in patients with PV have shown that ropeginterferon alfa-2b (ropeg-IFN) treatment is safe, efficacious, and reduces JAK2 V617F allele burden. As PV mainly affects individuals aged 60 years and older, incidence estimates have been increasing. Here we report 3 cases of elderly patients treated with ropeg-IFN who experienced no serious adverse events. All 3 patients achieved and maintained complete hematologic response with reduced JAK2 V617F allele burden. Ropeg-IFN is an effective and safe therapy for elderly patients with PV that also improves quality of life.
    Keywords:  Elderly; JAK2 V617F allele burden; Polycythemia vera; Ropeginterferon alfa-2b
    DOI:  https://doi.org/10.11406/rinketsu.67.214
  3. Blood. 2026 Apr 02. 147(14): 1513-1515
    Venetoclax in myeloma: t(11;14) and what else?
    Catherine Pellat-Deceunynck.
      
    DOI:  https://doi.org/10.1182/blood.2025032670
  4. Blood. 2026 Apr 02. 147(14): 1510-1511
    Breaking new ground with antibody-drug conjugates in myeloma.
    Saad Z Usmani.
      
    DOI:  https://doi.org/10.1182/blood.2025032443
  5. Rinsho Ketsueki. 2026 ;67(3): 205-208
    [Sustained hematologic complete response after discontinuation of ropeginterferon alfa-2b in patients with polycythemia vera].
    Masaki Maruta, Kento Mori, Koji Oka, Yuya Masuda, Junichi Kato, Tatsuya Konishi, Shogo Nabe, Yukihiro Miyazaki, Toshiki Ochi, Jun Yamanouchi, Katsuto Takenaka.
      We report two cases of polycythemia vera (PV) treated with ropeginterferon alfa-2b (ropeg-IFN) in which hematologic control was maintained without therapy after treatment discontinuation. The patients achieved complete response (CR) at 14 and 22 weeks after treatment initiation, respectively. After discontinuation of ropeg-IFN, Patient 1 has maintained hematocrit (Ht) <45% for 3 years and 3 months, while patient 2 has maintained CR for 1 year and 5 months. Clinical trials have demonstrated that ropeg-IFN reduces the JAK2 V617F allele burden, which is recognized as an independent risk factor for disease progression and thrombosis, apart from traditional factors such as age and prior cardiovascular events. To improve the prognosis of PV, it is essential to accumulate clinical evidence on trends in JAK2 V617F allele burden and the conditions required to maintain hematologic control after discontinuation of ropeg-IFN therapy in real-world settings.
    Keywords:  JAK2 V617F allele burden; Polycythemia vera; Ropeginterferon alfa-2b
    DOI:  https://doi.org/10.11406/rinketsu.67.205
  6. Rinsho Ketsueki. 2026 ;67(3): 209-213
    [Sustained molecular response after discontinuation of ropeginterferon alfa-2b in a young patient with polycythemia vera].
    Daigo Akahane, Meiko Kuriyama, Kai Osone, Yuya Arai, Shohei Wakamatsu, Shunsuke Ohtuki, Mitsuru Moriyama, Michiyo Asano, Seiichiro Katagiri, Seiichiro Yoshizawa.
      Ropeginterferon alfa-2b (ropeg-IFN), a treatment that allows for prolonged dosing intervals through site-specific PEGylation, has been approved for the treatment of polycythemia vera (PV) in patients for whom existing therapies are insufficient or unsuitable. In this case report, we describe a woman in her thirties who was treated with ropeg-IFN. Blood tests showed increased levels of all three blood cell lineages, and PV was diagnosed following bone marrow examination. The patient was enrolled in a clinical study in which she received ropeg-IFN because phlebotomy could not be performed due to difficulty with securing peripheral vascular access. Complete hematologic response (CHR) was achieved 12 weeks after the start of administration, and molecular response (MR) with a JAK2 V617F allele burden of <1% was achieved after approximately 156 weeks of continuous administration of ropeg-IFN. Alopecia (grade 1) occurred as an adverse event, but resolved after ropeg-IFN dose reduction. The patient maintained CHR and MR for 2 years following treatment discontinuation. We also discuss the potential benefit of ropeg-IFN in low-risk PV patients who were not previously considered candidates for aggressive cytoreductive therapy.
    Keywords:  Allele burden; Alopecia; Polycythemia vera; Ropeginterferon alfa-2b
    DOI:  https://doi.org/10.11406/rinketsu.67.209
  7. Ther Adv Hematol. 2026 ;17 20406207261431904
    Neutrophil-to-lymphocyte ratio half reduction as a surrogate of molecular response in polycythemia vera treated with ropeginterferon alfa-2b.
    Seug Yun Yoon, Sung-Soo Yoon, Deok-Hwan Yang, Gyeong-Won Lee, Sang Kyun Sohn, Ho-Jin Shin, Sung Hwa Bae, Chul Won Choi, Eun-Ji Choi, June-Won Cheong, Soo-Mee Bang, Joon Seong Park, Yong Park, Young Hoon Park, Sung-Eun Lee.
       Background: Polycythemia vera (PV) is a myeloproliferative neoplasm driven by JAK2 V617F mutations. Ropeginterferon alfa-2b effectively reduces both hematologic parameters and JAK2 allele burden, but molecular monitoring is not always readily available.
    Objectives: To evaluate whether a ⩾50% reduction in the neutrophil-to-lymphocyte ratio (NLR) can serve as a surrogate marker of hematologic and molecular response during ropeginterferon therapy.
    Design: Secondary analysis of a multicenter, phase II, open-label trial in South Korea.
    Methods: Ninety-five patients with PV received ropeginterferon alfa-2b biweekly for 48 weeks. NLR and JAK2 allele burden were serially measured, and generalized estimating equations and logistic regression were used to assess associations.
    Results: NLR half reduction significantly predicted hematologic response (week 24 OR 6.42, p = 0.001) and molecular response consistently across all time points (week 24 OR 27.94, p < 0.001).
    Conclusion: NLR half reduction is a simple, cost-effective biomarker that may reflect molecular response and treatment efficacy in PV.
    Keywords:  molecular response; neutrophil-to-lymphocyte ratio; polycythemia vera; ropeginterferon alfa-2b
    DOI:  https://doi.org/10.1177/20406207261431904
  8. Blood. 2026 Mar 31. pii: blood.2026033126. [Epub ahead of print]
    Lenalidomide plus rituximab for previously untreated advanced follicular lymphoma: the 10-year RELEVANCE trial analysis.
    Nicolas Gower, Pierre Feugier, Jason R Westin, Jean-Marc Schiano Schiano de Colella, Hervé Tilly, M Lia Palomba, Edith Julia, Gandhi Laurent Damaj, Amandine Durand, Ian W Flinn, François Lemonnier, Nadine Morineau, Loic Ysebaert, Nancy Bartlett, Catherine Thieblemont, Vincent Ribrag, Thomas Gastinne, Dony Arthur, Ludovic Fouillet, Stephanie Guidez, Roch Houot, Maria Gomes da Silva, Jeffrey Barnes, Fontanet Bijou, Guillaume Cartron, Alejandro Martin Martin Garcia-Sancho, Herbert A Eradat, Morgane Cheminant, Armando Lopez López-Guillermo, Pau Abrisqueta, Julie Abraham, Clémentine Sarkozy, Koji Izutsu, Gilles Crochet, Laurie H Sehn, Argyrios Gkasiamis, Marie-Laurence Yge, Loic Chartier, Nathan H Fowler, Luc Xerri, Gilles A Salles, Franck Morschhauser.
      In the multinational, phase 3 RELEVANCE trial, 1,030 patients with previously untreated follicular lymphoma were randomized to receive rituximab plus lenalidomide (R2; n=513) or rituximab-based immunochemotherapy (R-Chemo; n=517). In the final analysis, at 120 months of follow-up, median PFS was comparable between the treatment groups: 110.6 months with R2 versus 102.8 months with R-Chemo, according to Independent Review Committee assessment. The 10-year PFS rates were 46.4% and 46.6%, respectively. Median overall survival (OS) and time-to-next lymphoma treatment (TTNLT) were not reached in either arm; 10-year OS rates were 82.4% and 81.1%, respectively, and 10-year TTNLT rates were 62.2% and 66.3%, respectively. Overall, patients with POD24 had a poorer prognosis compared to those without POD24 (HR, 6.215; P<0.0001); however, no difference was observed between the study groups. The incidence of second primary malignancies (SPMs) was 2.11 cases per 100 patient-years (95% CI, 1.80-2.46). Only 9 transformations occurred after 24 months (3 with R2 versus 6 with R-chemo). In each study group, 87 patients died, mainly due to lymphoma progression and SPMs. This long-term follow-up of RELEVANCE confirmed that R2 provides a chemo-free alternative to immunochemotherapy in this patient population. Trial registration: NCT01476787 and NCT01650701; EudraCT: 2011-002792-42.
    DOI:  https://doi.org/10.1182/blood.2026033126
  9. Haematologica. 2026 Apr 02.
    Relapsed classic Hodgkin lymphoma; should all patients receive an autologous stem cell transplant? - the PRO.
    Chathuri Abeyakoon, John Kuruvilla.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2026.300574
  10. Blood. 2026 Apr 02. 147(14): 1511-1513
    Turning off SP140 to turn on HSCs.
    Sarah Juster, Berthold Göttgens.
      
    DOI:  https://doi.org/10.1182/blood.2025032459
  11. Leukemia. 2026 Mar 30.
    BCR::ABL1 tyrosine kinase inhibitors induce ribosome collisions to activate ZAK-dependent ribotoxic stress and apoptosis in chronic myeloid leukemia.
    Jumin Park, Soo-Hyun Kim, Jongmin Park, Heeju Park, Hongtae Kim, Dong-Wook Kim, Chunghun Lim.
      Ribosome collisions act as molecular sensors of cellular stress, yet their role in disease physiology remains unclear. Here, we demonstrate that inhibition of the oncogenic kinase BCR::ABL1 in chronic myeloid leukemia (CML) cells induces ribosome collisions and activates the ribotoxic stress response (RSR). Clinical analyses revealed that CML progression from the chronic phase to the aggressive blast phase correlated with elevated expression of the RSR-initiating kinase ZAK. Although ZAK sustained CML cell proliferation by promoting AKT activity, loss of ZAK function paradoxically reduced the cytotoxic effects of BCR::ABL1 inhibitors. Mechanistically, BCR::ABL1 inhibition promoted phosphorylation of eukaryotic translation elongation factor 2 (EEF2) via the mTOR-EEF2K pathway, slowed translation elongation, and generated nuclease-resistant collided ribosomes that triggered ZAK-dependent p38 activation and apoptosis. Furthermore, pharmacological modulation of translation flux fine-tuned the efficacy of BCR::ABL1 inhibitors, including in primary patient cells. These findings define a ribosome-based stress pathway crucial for CML apoptosis and highlight ZAK-dependent RSR as a therapeutic vulnerability.
    DOI:  https://doi.org/10.1038/s41375-026-02916-3
  12. Blood Adv. 2026 Apr 14. 10(7): 2406-2407
    A different alternative to warfarin?
    James H Morrissey.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2025019370
  13. Blood Adv. 2026 Mar 31. pii: bloodadvances.2025018310. [Epub ahead of print]
    Final phase 2 study results of acalabrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia.
    Richard R Furman, William G Wierda, Piers Em Patten, Jorge M Chaves, Jennifer R Brown, Talha Munir, Peter Martin, Farrukh T Awan, Deborah M Stephens, Paolo Ghia, Jacqueline Claudia Barrientos, Krish Patel, Jennifer A Woyach, Marianne de Borja, Min-Hui Wang, Nitin Jain, Susan M O'Brien, John C Byrd.
      Acalabrutinib is a selective, covalent Bruton tyrosine kinase inhibitor approved for marketing in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). We report final, long-term phase 1/2 study (NCT02029443) results in 99 patients with treatment-naive (TN) and 134 with relapsed/refractory (R/R) CLL/SLL. At final data cutoff, 71% and 31% of patients in the TN and R/R cohorts, respectively, remained on acalabrutinib treatment (median follow-up of 73.7 and 52.6 months). Among events of clinical interest (any grade) in the TN and R/R cohorts, atrial fibrillation was reported in 6.1% and 9.0%, hypertension in 29.3% and 23.1%, other malignancies (excluding non-melanoma skin cancer) in 14.1% and 17.2%, and major bleeding in 8.1% and 8.2% of patients, respectively. The incidence of the most common adverse events decreased over time. Overall response rates were 97.0% and 94.8% in the TN and R/R cohorts, respectively, with similar response findings among patients with standard and high-risk genomic features. In the TN cohort, median progression-free survival (PFS) was not reached and the 72-month PFS rate was 86.7% (95% confidence interval [CI] 77.0, 92.5). For the R/R cohort, median PFS was 66.1 months (range 0.4-87.8) and the 72-month PFS rate was 45.1% (95% CI 35.6, 54.1). This final analysis extends the duration of benefit seen with acalabrutinib, demonstrates that no new safety signals are apparent with longer follow-up, and confirms the safety and tolerability of acalabrutinib monotherapy in patients with CLL/SLL.
    DOI:  https://doi.org/10.1182/bloodadvances.2025018310
  14. Blood Adv. 2026 Apr 02. pii: bloodadvances.2025019036. [Epub ahead of print]
    BCMA/CD19 dual-targeting CAR T cell therapy in older patients with newly diagnosed multiple myeloma: a phase I study.
    Jin Liu, Xiaoqiang Fan, Liying Peng, Jia Liu, Haiyan He, Wanting Qiang, Lina Jin, Lang Shi, Jing Lu, Pei Guo, Nina Shah, Qi Zhang, Lianjun Shen, Juan Du.
      GC012F, now renamed AZD0120, is an autologous B-cell maturation antigen (BCMA) and CD19 dual-targeting CAR T cell product manufactured on the novel FasTCAR® platform. CAR T cell therapy has not been routinely studied in older patients with newly diagnosed multiple myeloma (NDMM). Therefore, we conducted a trial to assess AZD0120 as a frontline therapy for MM patients age ≥70. In this single-arm phase 1 study, NDMM patients age ≥70 received two cycles of VRD (bortezomib/lenalidomide/dexamethasone) induction therapy followed by AZD0120 infusion at the dose of 1.5x105 or 3x105 cells/kg. A total of 8 patients received AZD0120, with 4 classified as frail according to the Intergroupe Francophone du Myelome Simplified Frailty Score criteria, while the remaining 4 were non-frail patients. At a median follow-up of 9.8 months post-infusion, hematologic toxicities being the most common ≥grade 3 treatment-emergent adverse events (TEAEs), including lymphopenia (25%), leukopenia (50%), and neutropenia (75%). Four (50%) patients had cytokine release syndrome (CRS), all grade 1. No immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. All patients achieved stringent complete response (sCR) and all patients achieved minimal residual disease (MRD) negativity by Euroflow (10-6) at 1 month, with MRD negativity rates of 100% among evaluable patients at month 6 (n=7) and month 12 (n=2). Two patients in the frail subgroup with ECOG status of 2 recovered to ECOG status of 1 post-infusion. AZD0120 dual-targeting fast CAR T shows promising preliminary efficacy and a manageable safety profile for older patients with NDMM. NCT05840107.
    DOI:  https://doi.org/10.1182/bloodadvances.2025019036
  15. Blood Adv. 2026 Apr 14. 10(7): 2349-2350
    Refining prognostic tools in Waldenström macroglobulinemia.
    Anath C Lionel, Sheeba K Thomas.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2025019212
  16. Cancer. 2026 Apr 01. 132(7): e70372
    Hypomethylating agents plus venetoclax in younger acute myeloid leukemia: Meta-analysis of a shifting treatment paradigm.
    Salvatore Perrone, Laura De Fazio, Sebastian Monachetti, Matteo Molica.
       BACKGROUND: In younger, fit patients with acute myeloid leukemia (AML), intensive chemotherapy (IC) followed by consolidation or allogeneic hematopoietic stem cell transplantation (HSCT) is the standard approach. The authors performed a systematic review and meta-analysis to evaluate younger patients with AML treated with hypomethylating agents (HMA) plus venetoclax.
    METHODS: This systematic review and meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MEDLINE and the Cochrane Library were systematically searched through February 2026. Studies included AML patients with a median age <70 years treated with HMA/venetoclax. Primary outcomes were complete remission (CR/CRi) rate, measurable residual disease (MRD) negativity, 1-year overall-survival (OS), 1-year event-free survival (EFS), and rates of HSCT.
    RESULTS: Eight studies (two randomized controlled trials, two phase 2 trials, and four real-world studies), comprising 429 patients with a mean age of 54 years, were included. The pooled CR/CRi rate was 66% (95% confidence interval [CI], 48%-85%), with an MRD-negative rate of 69% (95% CI, 49%-90%). The pooled 1-year OS was 75% (95% CI, 63%-86%), exceeding Surveillance, Epidemiology, and End Results database cohorts (62%). The 1-year EFS was 59% (95% CI, 53%-65%), with low between-study heterogeneity. Overall, 66% of patients successfully proceeded to HSCT. Meta-regression analyses suggested a trend toward improved EFS and OS in studies using decitabine than azacitidine.
    CONCLUSIONS: In younger patients with AML, HMA plus venetoclax yielded high response rates, MRD negativity, and a substantial proportion of patients proceeding to HSCT. These findings support HMA/venetoclax as an effective induction strategy in selected younger patients and provide a rationale for prospective randomized trials comparing this approach with IC-based regimens.
    Keywords:  AML; azacitidine; decitabine; meta‐analysis; venetoclax
    DOI:  https://doi.org/10.1002/cncr.70372
  17. Haematologica. 2026 Apr 01. 111(4): 1147-1148
    Azacitidine for MDS and CMML.
    Emma St Martin, Mrinal M Patnaik.
      
    DOI:  https://doi.org/10.3324/haematol.2026.289398
  18. Eur J Pharmacol. 2026 Mar 27. pii: S0014-2999(26)00294-3. [Epub ahead of print]1021 178812
    Precision targeting of CD38 in immune thrombocytopenia: Mechanistic foundations and therapeutic implications.
    Xin Zhou, Yulu Liu, Peipei Zhang, Ningning Shan.
      Immune thrombocytopenia (ITP) is a multifactorial autoimmune disorder in which antibody-mediated platelet clearance and impaired megakaryopoiesis converge to drive thrombocytopenia and bleeding risk. Guideline-recommended first-line therapies often induce transient responses, yet durable remission is uncommon and many patients remain exposed to relapsing or refractory disease. A central mechanism of persistence is the trafficking of spleen-derived, antigen-specific plasmablasts to the bone marrow, where they differentiate into long-lived plasma cells that sustain antiplatelet autoantibody production. CD38, a multifunctional ectoenzyme and surface receptor expressed on plasma cells, B cells, NK cells, macrophages, and activated T cells, integrates NAD+/Ca2+ signalling with cellular crosstalk within these niches. CD38-directed monoclonal antibodies offer a rational strategy to target this terminal autoantibody reservoir while reshaping effector pathways: they deplete plasmablasts and plasma cells, attenuate Fcγ receptor-mediated phagocytosis, and modulate cytotoxic lymphocyte activity, collectively promoting platelet recovery. This review synthesises CD38 biology in the context of ITP pathogenesis, evaluates the emerging clinical evidence for CD38-targeted interventions, and outlines how biomarker-guided, combination-based strategies might redefine future treatment algorithms.
    Keywords:  Anti-CD38 monoclonal antibody; Immune thrombocytopenia; Long-lived plasma cells
    DOI:  https://doi.org/10.1016/j.ejphar.2026.178812
  19. Nat Commun. 2026 Mar 28.
    Zanubrutinib-rituximab followed by shortened chemoimmunotherapy as frontline treatment for mantle cell lymphoma (CHESS): a phase II trial.
    Yuchen Zhang, Man Nie, Yi Cao, Zhiming Li, He Huang, Guowei Li, Xiuhua Sun, Panpan Liu, Yan Gao, Xiaojie Fang, Bing Bai, Jun Cai, Lirong Li, Yingxian Liu, Sihua Peng, Huiqiang Huang, Yi Xia, Qingqing Cai.
      A combination of Bruton's tyrosine kinase (BTK) inhibitor ibrutinib and rituximab has shown promising efficacy in mantle cell lymphoma (MCL). This phase II trial evaluated the second-generation BTK inhibitor zanubrutinib plus rituximab as induction, followed by shortened chemoimmunotherapy as frontline treatment for MCL (NCT04624958). Eligible patients had histologically confirmed stage II-IV disease requiring immediate therapy and no prior MCL-related systemic treatment. Patients received zanubrutinib-rituximab for up to 12 cycles (part A); those achieving a complete response (CR) or experiencing disease progression proceeded to four cycles of R-DHAOx (rituximab, dexamethasone, cytarabine, and oxaliplatin) (part B). Patients with CR after part B received zanubrutinib maintenance for one year. The primary endpoint was the CR rate at part A completion. Forty-two patients were enrolled. The CR rate at part A completion was 88% (95% confidence interval [CI], 74-96), and 86% (95% CI, 72-95) at part B completion. Hematologic toxicities predominated: the most common grade 3-4 adverse events were neutropenia (7%) in part A, and thrombocytopenia (77%) and neutropenia (49%) in part B. In conclusion, zanubrutinib-rituximab induction followed by shortened R-DHAOx is efficacious with manageable safety as frontline therapy for MCL. This strategy allows for a reduction in chemotherapy cycles and warrants validation in randomized controlled trials.
    DOI:  https://doi.org/10.1038/s41467-026-71241-1
  20. Leuk Lymphoma. 2026 Apr 01. 1-16
    Single-cell technologies in deciphering drug resistance of multiple myeloma: mechanistic insights and clinical translation prospects.
    Jun Wu, Haibo Dong, Xuejing Xu, Mei Wang.
      The greatest hindrance to long-lasting remission in multiple myeloma (MM) is drug resistance and is modulated by the complex interaction of tumor-intrinsic plasticity and microenvironmental co-evolution. Multi-omics of single cells has transformed the exploration of this complexity, and has solved the dynamics of clonal architecture and ecosystem at an unprecedented resolution. The present review summarizes critical relapse-driver revealed by single cell technologies, including existing resistant subclones and non-genetic programs, as well as inflammatory stromal remodeling and immune exhaustion. We also discuss the problem of reproducibility crisis due to analytical heterogeneity critically, outlining computational best practices to distinguish robust biological signals to technical artifacts. Moreover, we comment on the translational imperative, emphasizing new target discovery, rational combination strategies and mechanism-based prognostic modeling. Ultimately, high-fidelity molecular profiling needs to be bridged with strict analytical principles to make precision oncology advance in MM.
    Keywords:  Multiple myeloma; clinical application; drug resistance; mechanisms; single-cell technologies
    DOI:  https://doi.org/10.1080/10428194.2026.2649879
  21. Ann Acad Med Singap. 2026 Mar 24.
    Primary sinonasal DLBCL: High prevalence of MCD subtype and CNS risk.
    Shuai Tan, Yaofang Cao, Hong Zhao, Jing Ni, Qiang Ma, Yixian Guo, Dongmei Zou, Wuhan Hui, Mingyue Shang, Huizhen He, Yuxin Li, Li Su, Wanling Sun.
      
    Keywords:  CNS prophylaxis; CNS risk; molecular feature; primary sinonasal diffuse large B-cell lymphoma; survival
    DOI:  https://doi.org/10.47102/annals-acadmedsg.2025407
  22. Hum Cell. 2026 Mar 30. pii: 55. [Epub ahead of print]39(4):
    Arginine deprivation induces ROS dependent autophagic cell death in human acute myeloid leukemia cells.
    Fatima Taki, Mirna Farhat, Oula El-Atat, Sarah Al-Samman, Nicole Assaf, Ralph J Abi-Habib.
      In this study, we assess the activation of autophagy and its impact on cytotoxicity following [HuArgI (Co)-PEG5000]-induced arginine deprivation in AML cells. We have previously shown that arginine deprivation is selectively cytotoxic to AML cells and that cell death is caspase independent and non-apoptotic, hence the mechanism of cell death remained elusive. We tested a panel of 7 AML cell lines, and we first demonstrated that the cytotoxicity of [HuArgI (Co)-PEG5000] to AML cells is long-term and sustained despite re-expression of overexpression of ASS1 in all cell lines. We also demonstrated that arginine deprivation leads to a prolonged and extensive activation of autophagy starting at 24 and lasting up to 120 h in all cells. Autophagy was shown to induce cell death since its inhibition using chloroquine (CQ) significantly decreased [HuArgI (Co)-PEG5000]-induced cytotoxicity, indicating autophagic cell death in AML cells following arginine deprivation. Moreover, we showed that arginine deprivation leads to ROS accumulation and that neutralizing ROS using N-acetylcysteine (NAC) does not affect the autophagic response but completely reverses the cytotoxicity of arginine deprivation, demonstrating that death by autophagy is dependent on ROS generation in AML cells.
    Keywords:  Acute myeloid leukemia; Arginine deprivation; Autophagy; Death by autophagy; ROS-induced cell death; [HuArgI (Co)-PEG5000]
    DOI:  https://doi.org/10.1007/s13577-026-01370-8
This page is being maintained by Thomas Krichel. It was last updated on 2026‒05‒11 at 13:33.