bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–05–31
twenty-two papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy.
  2. Assessment of Transitioning from High-Potency to Low-Potency Inhibitors in Chronic Myeloid Leukemia (CML) Patients: The Downgrading-Impact (D-IMPACT) Project.
  3. IL-16 production is a mechanism of resistance to BTK inhibitors and R-CHOP in lymphomas.
  4. Long-Term Outcomes of Azacitidine, Venetoclax and Gilteritinib in Newly Diagnosed FLT3-Mutated AML.
  5. Improving salvage regimens prior to autologous stem cell transplantation in relapsed/refractory Hodgkin's lymphoma patients: updates in the novel therapy era.
  6. CD117-targeted HCT preconditioning in AML and MDS.
  7. An Evaluation of Ibrutinib and Ixazomib in Patients With Relapsed/Refractory Mantle Cell Lymphoma: PrE0404.
  8. Long-term outcomes of low-dose dasatinib in older patients with chronic myeloid leukemia in chronic phase: an extended follow-up of the DAVLEC phase 2 trial.
  9. Nivolumab with or without vinblastine for first-line treatment of elderly patients with Hodgkin lymphoma and coexisting medical conditions: the Niviniho phase II Lysa study.
  10. Interferon in early MF: intersection of biology and evidence.
  11. Translating advances in primary central nervous system lymphoma: from prognostic stratification to treatment innovation.
  12. Polycythemia Vera and Cardiovascular Disease: A Mini Review.
  13. Chronic Lymphocytic Leukemia Through the Spectrum: Frontline Therapy, Sequencing With Subsequent Therapy, and Treatment of Double-Refractory Patients.
  14. A first-in-class bifunctional antibody targeting CD20 and CD37 remodels the immune microenvironment in relapsed or refractory B-cell malignancies.
  15. Redefining Early Relapse in Multiple Myeloma - Time to Change the Rules.
  16. A multicentre randomized open-label phase 2 trial of dexamethasone plus glycyrrhizinate versus dexamethasone in newly diagnosed immune thrombocytopenia.
  17. Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials.
  18. Iron Deficiency and Oral Treatments: Limitations, Pharmacokinetics, and the Role of Iron Protein Succinylate in Clinical Practice.
  19. DUSP1 is a Key Driver of Disease Persistence and Potential Therapeutic Target in Hairy Cell Leukemia.
  20. A Comprehensive Echocardiographic Assessment of Patients With Chronic Myeloid Leukemia on Dasatinib.
  21. Smoldering Multiple Myeloma: Early Intervention or Structured Surveillance? A Comprehensive Review of Evidence for and Against Early Therapy.
  22. Chewing the fat: the role of total cholesterol in MPN management.
  1. N Engl J Med. 2026 May 29.
    Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy.
    MajesTEC-9 Trial Investigators
       BACKGROUND: The efficacy of teclistamab, a bispecific antibody targeting B-cell maturation antigen and CD3, as early-line monotherapy in relapsed or refractory multiple myeloma is unclear.
    METHODS: We randomly assigned patients with relapsed or refractory multiple myeloma who had previously received one, two, or three lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide, to receive teclistamab or the investigator's choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd). Antimicrobial prophylaxis and immune globulin replacement were recommended. The primary end point was progression-free survival as assessed by an independent review committee.
    RESULTS: A total of 296 patients were assigned to teclistamab and 297 to PVd or Kd. At the interim analysis (median follow-up, 17.3 months), teclistamab significantly improved progression-free survival as compared with PVd or Kd (estimated 18-month progression-free survival, 69.8% vs. 26.9%; hazard ratio for disease progression or death, 0.29; 95% confidence interval [CI], 0.23 to 0.38; P<0.001). The percentage of patients with a complete response or better was higher with teclistamab than with PVd or Kd (65.9% vs. 16.8%, P<0.001). Overall survival was improved with teclistamab as compared with PVd or Kd (estimated 18-month overall survival, 79.2% vs. 68.6%; hazard ratio for death, 0.60; 95% CI, 0.43 to 0.83; P = 0.002). Adverse events of grade 3 or 4 occurred in 84.9% of teclistamab recipients and in 76.3% of PVd or Kd recipients, with grade 5 adverse events in 6.5% and 3.5%, respectively. Cytokine release syndrome, mostly of grade 1 or 2, occurred in 66.0% of teclistamab recipients, and immune effector cell-associated neurotoxicity syndrome occurred in 4.1%. Grade 3 or 4 infection occurred in 41.6% of teclistamab recipients and in 29.0% of PVd or Kd recipients.
    CONCLUSIONS: Among patients with multiple myeloma and one to three previous lines of therapy, teclistamab significantly improved progression-free and overall survival as compared with PVd or Kd. Infections of grade 3 or 4 were common. (Funded by Johnson & Johnson; MajesTEC-9 ClinicalTrials.gov number, NCT05572515.).
    DOI:  https://doi.org/10.1056/NEJMoa2603870
  2. Cancers (Basel). 2026 May 20. pii: 1656. [Epub ahead of print]18(10):
    Assessment of Transitioning from High-Potency to Low-Potency Inhibitors in Chronic Myeloid Leukemia (CML) Patients: The Downgrading-Impact (D-IMPACT) Project.
    Elisabetta Abruzzese, Monica Crugnola, Luca Garuffo, Uros Markovic, Malgorzata Monika Trawinska, Sara Barulli, Alessandro Maggi, Sara Galimberti, Daniele Cattaneo, Daniele Sannipoli, Mariella D'Adda, Elena Chiara, Massimiliano Bonifacio, Antonella Vita Russo Rossi, Germana Beltrami, Sabina Russo, Elena Crisà, Grazia Sanpaolo, Francesco Cavazzini, Giuseppina Loglisci, Carmen Fava, Valentina Giai, Anna Rita Scortechini, Barbara Scappini, Matteo Dalmazzo, Gianni Binotto, Monica Bocchia, Davide Facchinelli, Ambra Di Veroli, Sara Pasquina Pascale, Annapaola Leporace, Simona Bernardi.
      Background: Since the advent of imatinib, more potent next-generation tyrosine kinase inhibitors (TKIs) and asciminib have expanded therapeutic options for chronic myeloid leukemia (CML). Treatment-free remission (TFR) is an important goal in CML management, but only ~30% of patients can achieve it, leaving many on lifelong therapy. TKIs are usually used in escalating order of potency, but in patients ineligible for or failing TFR, "downgrading" to safer, lower-potency agents may be advantageous. Methods: We analyzed this strategy in 157 patients across 29 Italian CML Campus centres. Data were collected via e-forms in July 2024. Prognostic scores at diagnosis did not influence downgrading. Results: The most downgraded TKIs were nilotinib (47%) and dasatinib (37%). Imatinib was the most frequent target agent (69.7%), followed by nilotinib and bosutinib. The majority underwent downgrading during first-line therapy and most after prior dose de-escalation. Adverse events were the leading reason for downgrading (79%). Notably, in 52.6% of cases, molecular responses improved afterwards. Twenty-one patients subsequently attempted TFR, with 17 (81%) remaining treatment-free at a median follow-up of 22 months. Conclusions: These results show that, beyond the known role of de-escalation, downgrading represents a new, feasible approach to maintaining long-term control, limiting toxicity and costs, and favouring TFR.
    Keywords:  CML; TKIs; dose; down-grading
    DOI:  https://doi.org/10.3390/cancers18101656
  3. Blood. 2026 May 29. pii: blood.2025029956. [Epub ahead of print]
    IL-16 production is a mechanism of resistance to BTK inhibitors and R-CHOP in lymphomas.
    Alberto J Arribas, Eleonora Cannas, Giulio Sartori, Francesca Guidetti, Luciano Cascione, Sara Napoli, Gabriela Forestieri, Federica Fuzio, Emma Daniela Susanna Pesenti, Chiara Tarantelli, Filippo Spriano, Antonella Zucchetto, Francesca Maria Rossi, Alessio Bruscaggin, Andrea Rinaldi, Manuel Castro de Moura, Sandra Jovic, Andrea Raimondi, Roberta Bordone Pittau, Lodovico Terzi di Bergamo, Xiaofei Ye, Anastasios Stathis, Yaacov Ben-David, Qiang Pan-Hammarström, Federico Simonetta, Georg Stussi, Emanuele Zucca, Valter Gattei, Jennifer R Brown, Manel Esteller, Davide Rossi, Francesco Bertoni.
      Resistance to Bruton tyrosine kinase (BTK) inhibitors remains a major clinical challenge in B-cell lymphomas and often occurs in the absence of BTK or PLCG2 mutations. Here, we investigated non-genetic mechanisms of ibrutinib resistance in marginal zone lymphoma (MZL) and their broader therapeutic implications. Chronic ibrutinib exposure generated a resistant MZL model that showed cross-resistance to BTK inhibitors and degraders, without evidence of multidrug resistance or genetic alterations. Integrated transcriptomic, epigenetic, and proteomic analyses revealed extensive reprogramming, including activation of PI3K/AKT, MAPK, and MYC pathways, repression of apoptosis and oxidative phosphorylation, and a prominent cytokine-secretory phenotype. Interleukin-16 (IL-16) emerged as a central mediator of resistance. IL-16 was transcriptionally upregulated, actively secreted, and sufficient to induce ibrutinib resistance across multiple CD9-positive models of MZL, mantle cell lymphoma, chronic lymphocytic leukemia (CLL), and activated B-cell-like diffuse large B-cell lymphoma. Serum IL-16 levels were elevated in ibrutinib-refractory CLL patients without BTK/PLCG2 mutations. Mechanistically, IL-16 engaged CD9-enriched membrane microdomains to activate PI3Kδ, thereby sustaining AKT and ERK signaling, stabilizing MYC, inducing NF-κB-dependent programs, and upregulating antiapoptotic effectors, including BFL1 (BCL2A1). Pharmacological or genetic disruption of the IL-16/CD9/PI3K axis restored sensitivity to BTK inhibitors and R-CHOP and abrogated IL-16-induced signaling in primary CLL samples. In conclusion, an IL-16/CD9-driven, epigenetically regulated survival pathway represents one possible mechanism of resistance to BTK inhibitors and chemoimmunotherapy, supporting therapeutic targeting of this axis in refractory B-cell lymphomas.
    DOI:  https://doi.org/10.1182/blood.2025029956
  4. Blood Adv. 2026 May 27. pii: bloodadvances.2026019841. [Epub ahead of print]
    Long-Term Outcomes of Azacitidine, Venetoclax and Gilteritinib in Newly Diagnosed FLT3-Mutated AML.
    Nicholas J Short, Hagop M Kantarjian, Naval G Daver, Roberta S Azevedo, Omer Karrar, Courtney D DiNardo, Tapan M Kadia, Musa Yilmaz, Manuel M Maroun, Maria Catherine Rita Hachem, Gautam Borthakur, Ghayas C Issa, Elizabeth J Shpall, Uday R Popat, Xuelin Huang, Wei Qiao, Lewis Fady Nasr, Walid Macaron, Regina Abramova, Guillermo Garcia-Manero, Marina Konopleva, Farhad Ravandi.
      In patients with FLT3-mutated AML who receive frontline azacitidine plus venetoclax, relapses are commonly driven by expansion of the FLT3-mutated clone, providing rationale for "triplet" FLT3 inhibitor-based lower-intensity regimens. Here we report long-term outcomes of a phase II study of azacitidine, venetoclax and gilteritinib in adults with newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy. Thirty patients were treated; the median age was 71 years, and 22 (73%) had a FLT3-ITD mutation. The complete remission (CR)/CR with incomplete hematologic recovery rate was 96%, and 14 patients (47%) underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first remission. With a median follow-up of 41.5 months, 11 patients (37%) relapsed; in 67% of evaluable relapses, the FLT3 mutation was not detectable. The median RFS and OS were 23.4 and 29.7 months, respectively, and the 3-year RFS and OS rates were 43% and 46%, respectively. Among patients with FLT3-ITD-mutated AML, the median RFS and OS were 17.0 and 21.8 months, respectively, and the 3-year RFS and OS rates were 32% and 36%, respectively. The presence of a baseline RAS pathway mutation was associated with worse outcomes. Survival rates were similar regardless of HSCT in first remission. Among patients who received at least one consolidation cycle, 68% had a reduction in the dose or duration of at least one of the study drugs. The triplet regimen of azacitidine, venetoclax and gilteritinib is associated with durable remissions and encouraging long-term survival. Randomized studies comparing this regimen to standard of care approaches are warranted. This trial is registered at www.clinicaltrials.gov #NCT04140487.
    DOI:  https://doi.org/10.1182/bloodadvances.2026019841
  5. Expert Rev Hematol. 2026 May 29.
    Improving salvage regimens prior to autologous stem cell transplantation in relapsed/refractory Hodgkin's lymphoma patients: updates in the novel therapy era.
    Jowon Laura Kim, Ivana N Micallef.
       INTRODUCTION: Relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) has historically been managed with multi-agent salvage chemotherapy followed by autologous stem cell transplantation (ASCT). Recently, brentuximab vedotin (BV) and programmed cell death protein 1 (PD-1) inhibitors in the salvage setting have substantially improved response rates and post-transplant outcomes. A PubMed search was conducted to identify key studies evaluating salvage therapies in R/R transplant-eligible cHL.
    AREAS COVERED: This review summarizes conventional salvage regimens and modern BV/ PD-1 inhibitor-based strategies, including response-adapted approaches. Emerging data on chemotherapy-sparing regimens, retreatment after frontline PD-1 inhibitor exposure, and novel consolidation strategies are discussed. The evolving role of post-ASCT maintenance, circulating tumor DNA-guided response assessment, potential for ASCT omission in deep molecular remission, and the next generation of immunotherapeutic approaches for multiply relapsed disease are also reviewed.
    EXPERT OPINION: PD-1 inhibitor-based salvage regimens now represent the preferred strategy for many transplant-eligible patients, producing unprecedented complete response rates and durable disease control after ASCT. The next major advance will be biologically guided risk stratification using metabolic and molecular response measures to individualize consolidation and potentially omit ASCT in selected patients. Novel immune-based therapies are urgently needed for patients who relapse after BV and PD-1 inhibitor therapy.
    Keywords:  Autologous stem cell transplantation; PD-1 inhibitor; brentuximab vedotin; checkpoint inhibitors; classical Hodgkin lymphoma; nivolumab; pembrolizumab; relapsed or refractory disease; salvage therapy; transplant-eligible patients
    DOI:  https://doi.org/10.1080/17474086.2026.2683036
  6. Blood. 2026 May 28. 147(22): 2559-2560
    CD117-targeted HCT preconditioning in AML and MDS.
    Markus G Manz.
      
    DOI:  https://doi.org/10.1182/blood.2026033642
  7. Clin Lymphoma Myeloma Leuk. 2026 May 04. pii: S2152-2650(26)00139-4. [Epub ahead of print]
    An Evaluation of Ibrutinib and Ixazomib in Patients With Relapsed/Refractory Mantle Cell Lymphoma: PrE0404.
    Jonathon B Cohen, Craig A Portell, Mehdi Hamadani, Opeyemi Jegede, Catherine Diefenbach, Christopher Fletcher, Matthew Matasar, Daniel Landsburg, Suparna Mantha, Brad Kahl.
       INTRODUCTION: Management of relapsed mantle cell lymphoma (MCL) has included Bruton's tyrosine kinase (BTK) inhibitors for more than 10 years, but finding an optimal combination partner that meaningfully improves outcomes while limiting toxicity has been difficult. We conducted a phase 1/2 trial of ibrutinib and the proteasome inhibitor, ixazomib, in patients with relapsed/refractory MCL.
    PATIENTS AND METHODS: Patients and Methods: The primary endpoint for the phase 1 study was to determine the recommended phase 2 dose (RP2D), and for the phase 2 study was the complete response (CR) rate, compared with the previously reported single-agent CR rate of ibrutinib. After the phase 1 portion of the study identified a recommended phase 2 dose of ixazomib 4 mg days 1, 8, and 15, of a 28-day cycle combined with ibrutinib 560 mg daily until progression or unacceptable toxicity.
    RESULTS: We enrolled 35 BTK-naïve patients to the phase 2 portion of the study. Overall response rate was 77%, and 37% of patients achieved a CR. The 2-year progression-free survival is 44%, and the duration of response is 47%. Treatment-related adverse events were common, resulting in treatment discontinuation for 37% of patients.
    CONCLUSION: Given that the progression-free survival (PFS) was not significantly improved compared to historical reports for single-agent BTK inhibitors and the high rate of treatment-related toxicity, this combination does not merit further study in this setting. Additional trials evaluating newer BTK inhibitors and alternative combination partners are warranted.
    Keywords:  BTK inhibitors; Clinical trial; Non-Hodgkin lymphoma; Proteasome inhibitors; Targeted therapy
    DOI:  https://doi.org/10.1016/j.clml.2026.04.025
  8. Blood Cancer J. 2026 May 28. pii: 83. [Epub ahead of print]16(1):
    Long-term outcomes of low-dose dasatinib in older patients with chronic myeloid leukemia in chronic phase: an extended follow-up of the DAVLEC phase 2 trial.
    Hiroshi Ureshino, Kazunori Murai, Takashi Kumagai, Tatsuji Mino, Kaichi Nishiwaki, Satoshi Wakita, Tomoharu Takeoka, Masayuki Mita, Chikashi Yoshida, Nobuhiko Uoshima, Toshihiro Fukushima, Junya Kuroda, Takeshi Kondo, Masahiro Chiba, Takuya Miyazaki, Katsuhiro Io, Tomoaki Ueda, Takaaki Ono, Kensuke Usuki, Takahiro Yamauchi, Katsumichi Fujimaki, Takayuki Ikezoe, Atsushi Kawaguchi, Shinya Kimura.
      
    DOI:  https://doi.org/10.1038/s41408-026-01526-7
  9. Haematologica. 2026 May 28.
    Nivolumab with or without vinblastine for first-line treatment of elderly patients with Hodgkin lymphoma and coexisting medical conditions: the Niviniho phase II Lysa study.
    Julien Lazarovici, Sandy Amorim, Krimo Bouabdallah, Marguerite Fournier, Stéphanie Guidez, Lysiane Molina, Franck Morschhauser, Baptiste Delapierre, Thomas Gastinne, Kamel Laribi, Vincent Launay, Bohrane Slama, Nawel Belmecheri, René-Olivier Casasnovas, Anne Corby, Eric Durot, Pierre Feugier, Emmanuelle Nicolas-Virelizie, David Sibon, Alina Berriolo-Riedinger, Véronique Edeline, Thierry Vander Borght, Diane Damotte, Alexandra Traverse-Glehen, Vincent Ribrag, Marc André.
      The prognosis of elderly patients with Hodgkin lymphoma (HL) unfit for conventional chemotherapy remains poor. We report the results of the LYSA phase II NIVINIHO trial in treatment-naive HL patients aged ≥ 61 years with comorbidities contraindicating standard chemotherapy. Treatment included an induction phase with nivolumab alone, followed by a consolidation phase: either nivolumab monotherapy for patients with early complete metabolic response or nivolumab plus vinblastine for patients with stable disease or partial response. The primary objective of the study was the complete metabolic response (CMR) rate at the end of treatment. From August 2018 to April 2020, 64 patients were enrolled. Median age was 75.0 (range, 62 to 91) years, Ann Arbor stage was advanced (stage III-IV) in 75.0% of patients. At end of nivolumab induction, 11 patients (17.2%) achieved CMR and were consolidated with nivolumab alone, 23 (35.9%) patients obtained PMR or SD and received vinblastine plus nivolumab. Among the 56 evaluable patients, 16 (28.6%) achieved CMR at the end of treatment. With a median follow-up of 24.4 months (range, 0.9 to 35.2), median progression-free survival (PFS) was 9.8 months (95% confidence interval [CI], 4.2 to 12) while the 2-year overall survival (OS) rate was 74.1% (95%CI, 58.9% to 84.4%). Thirtytwo patients (50%) experienced grade ≥ 3 adverse events (AEs). Nivolumab-related adverse events led to treatment discontinuation in 19 patients (29.7%). Our results show that nivolumab can be administrated to elderly, frail patients unfit for classical chemotherapy; however, the objective response rate with monotherapy remains low. Trial registration number: NCT03580408.
    DOI:  https://doi.org/10.3324/haematol.2025.300166
  10. Blood Adv. 2026 Jun 09. 10(11): 3998-3999
    Interferon in early MF: intersection of biology and evidence.
    John Mascarenhas.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2026020389
  11. Front Oncol. 2026 ;16 1591328
    Translating advances in primary central nervous system lymphoma: from prognostic stratification to treatment innovation.
    Zhenjiang Pan, Jing Bao, Shepeng Wei.
      Primary central nervous system lymphoma (PCNSL) is a rare but aggressive diffuse large B-cell lymphoma confined to the CNS, characterized by unique clinical behavior and therapeutic challenges. Outcomes have improved with high-dose methotrexate (HD-MTX)-based regimens, but relapse, treatment toxicity, and age-related frailty remain major barriers. This review synthesizes advances in prognostic stratification and treatment of PCNSL. We highlight two validated clinical models (IELSG and MSKCC) and emerging genomic biomarkers that refine risk assessment. HD-MTX-based induction (MTR, R-MPV, MATRix, R-MBVP) is the standard first-line approach for fit patients, including many older adults. Consolidation with thiotepa-based high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) yields durable disease control in eligible patients, whereas non-myeloablative cytarabine-based chemotherapy or reduced-dose whole-brain radiotherapy remains an option for those unfit for transplant. In relapsed disease, methotrexate rechallenge benefits prior responders, while BTK- or IMiD-based regimens, CAR-T therapy, and focal or whole-brain radiotherapy are under active investigation. Maintenance with HD-MTX or targeted agents shows promise but requires validation. Although therapeutic outcomes have steadily improved, particularly with HD-MTX-based induction and HDC-ASCT consolidation, long-term survival for elderly and relapsed patients remains unsatisfactory. The integration of molecular biomarkers, neurotoxicity-sparing consolidation, and novel immunotherapies may further individualize treatment and improve the durability of remission.
    Keywords:  Bruton tyrosine kinase inhibitors; CAR-T cell therapy; autologous stem-cell transplantation; high-dose methotrexate; lymphoma; prognostic stratification; relapsed/refractory disease; whole-brain radiotherapy
    DOI:  https://doi.org/10.3389/fonc.2026.1591328
  12. Juntendo Med J. 2026 ;72(2): 189-192
    Polycythemia Vera and Cardiovascular Disease: A Mini Review.
    Mone Mukai, Tadao Aikawa, Yuya Matsue, Tohru Minamino.
      Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by clonal erythrocytosis driven by JAK2 mutations, affecting more than 95% of patients. Morbidity and mortality in PV are dominated by cardiovascular complications-particularly arterial and venous thrombosis. Modern treatment approaches, including therapeutic phlebotomy, low-dose aspirin, and cytoreductive therapies (hydroxyurea, interferon-α formulations, and ruxolitinib), have reduced blood cell counts and thrombotic risk, yet concerns about treatment-associated cardiovascular toxicity have emerged. Recent cardio-oncology guidelines emphasize structured monitoring for cancer therapy-related cardiovascular toxicity. This mini review summarizes the cardiovascular burden of PV, therapeutic strategies to mitigate risk, and emerging perspectives on cardiotoxicity-including a recently reported case of reversible left ventricular dysfunction associated with ropeginterferon α-2b.
    Keywords:  cardio-oncology; cardiotoxicity; cardiovascular disease; polycythemia vera; ropeginterferon α-2b
    DOI:  https://doi.org/10.14789/ejmj.JMJ25-0065-R
  13. Am Soc Clin Oncol Educ Book. 2026 Jun;46(3): e517476
    Chronic Lymphocytic Leukemia Through the Spectrum: Frontline Therapy, Sequencing With Subsequent Therapy, and Treatment of Double-Refractory Patients.
    Anna Maria Frustaci, Alessandra Tedeschi, Alexander F Vom Stein, Michael Hallek, Susan O'Brien.
      The rapid development of novel agents and combinations in chronic lymphocytic leukemia/small lymphocytic lymphoma has led to multiple options for frontline therapy and relapse, including continuous therapy and fixed duration regimens. The choice of therapy may be affected by the patient performance status, molecular abnormalities, potential side effects, logistics, patient expectations, and sequencing options in patients who will likely need more than one therapy in their lifetime. Current therapy options consist of several Bruton tyrosine kinase inhibitors (BTKis; covalent and noncovalent), one BCL-2 inhibitor (with others in development), and antibodies, with the possibility of single-agent therapy, doublets, or, less frequently, triplet therapy. In addition, treatment for double-refractory patients (refractory to both a BTKi and a BCL-2i) is available, but options are limited, so additional therapies for treatment in these high-risk patients are needed and in development.
    DOI:  https://doi.org/10.1200/EDBK-26-517476
  14. J Hematol Oncol. 2026 May 29.
    A first-in-class bifunctional antibody targeting CD20 and CD37 remodels the immune microenvironment in relapsed or refractory B-cell malignancies.
    Li Wang, Jiaying Liu, Keshu Zhou, Zengjun Li, Yun Zeng, Ying Qian, Yuping Sun, Hui Wu, Lindsay Roerker, Peter Tan, Chen Ma, Liwei Zhou, Xianlin Duan, Xiaoyan Kang, Weili Zhao.
       BACKGROUND: Bispecific antibodies engaging CD3 have transformed the treatment landscape of B-cell malignancies but remain constrained by T-cell overactivation and cytokine release. Here, we describe PSB202, a first-in-class bifunctional antibody co-targeting CD20 and CD37 to deplete malignant B cells independently of T-cell engagement.
    METHODS: In this multicenter, open-label phase Ia trial (NCT05003141), adults with relapsed or refractory (R/R) CD20⁺ B-cell non-Hodgkin lymphoma (B-NHL) received escalating doses of PSB202 from 12 to 300 mg. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary endpoints were safety, pharmacokinetics, pharmacodynamics, and efficacy.
    RESULTS: Fifteen heavily-pretreated patients were enrolled, with a median age of 67.7 years (range, 54-78). One DLT of grade 4 neutropenia occurred at 100 mg. MTD was not reached. PSB202 showed a manageable safety profile, with grade ≥ 3 neutropenia and leukopenia both occurring in 60% of patients. The overall response rate was 30% in 10 evaluable patients, including one complete response at 300 mg. PSB202 achieved sustained B-cell depletion and induced IFN-γ release without cytokine release syndrome. Single-cell sequencing revealed different immune microenvironments in responders and non-responders, and the treatment also induced alterations.
    CONCLUSIONS: PSB202 may represent a novel dual-targeting strategy that possibly mitigates CD3-related toxicity while promoting cytotoxic immune activation. These findings support further clinical development of PSB202 as an off-the-shelf therapeutic alternative for R/R B-NHL.
    TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov, NCT05003141.
    Keywords:  B-cell lymphoma; Bifunctional antibody; First-in-human; Pharmacodynamics; Pharmacokinetics; Phase I
    DOI:  https://doi.org/10.1186/s13045-026-01796-5
  15. N Engl J Med. 2026 May 29.
    Redefining Early Relapse in Multiple Myeloma - Time to Change the Rules.
    María-Victoria Mateos.
      
    DOI:  https://doi.org/10.1056/NEJMe2605404
  16. Br J Haematol. 2026 May 24.
    A multicentre randomized open-label phase 2 trial of dexamethasone plus glycyrrhizinate versus dexamethasone in newly diagnosed immune thrombocytopenia.
    Haoyi Wang, Ruting Wang, Chenglu Yuan, Kehong Bi, Taiwu Xiao, Qingliang Teng, Haiying Wang, Jie Yu, Ming Hou, Yu Hou.
      Standard first-line therapy with dexamethasone requires further optimization due to unsatisfying long-term outcomes in patients with primary immune thrombocytopenia (ITP). Previous research suggested that glycyrrhizinate induces platelet responses in ITP murine models. This study aimed to compare the efficacy and safety of dexamethasone plus glycyrrhizinate with dexamethasone in patients with newly diagnosed ITP. Eligible patients aged ≥18 years with newly diagnosed, treatment-naïve ITP who had baseline platelet count of <30 × 109/L were enrolled during routine outpatient visits. Recruited patients were randomly assigned 1:1 to receive either dexamethasone plus glycyrrhizinate (n = 55) or dexamethasone (n = 56). The modified intention-to-treat analysis included 96 patients (48 vs. 48) who received at least one dose of allocated treatments. The primary end-point overall response, defined as a platelet count of ≥30 × 109/L, at least doubling of baseline platelet count and no bleeding, was reached in more patients in combination group [56.25% (27/48)] than that in the monotherapy group [31.25% (15/48)] at month 6 (*p = 0.0231), with a longer duration of response, but not at day 14. The most common treatment-emergent adverse events were gastrointestinal reactions and anxiety. No grade 3-5 adverse events or deaths occurred. Dexamethasone plus glycyrrhizinate was an optimized initial therapy in ITP (NCT05023915).
    Keywords:  first‐line treatment; glycyrrhizinate; high‐dose dexamethasone; newly diagnosed; primary immune thrombocytopenia (ITP)
    DOI:  https://doi.org/10.1111/bjh.70574
  17. J Clin Oncol. 2026 May 29. JCO2600755
    Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials.
    CARES Investigators
       PURPOSE: In immunoglobulin light chain (AL) amyloidosis, amyloid fibrils cause organ dysfunction. Anselamimab, a monoclonal antibody, selectively binds to amyloid fibrils, accelerating their clearance.
    METHODS: Newly diagnosed patients with European modification of Mayo 2004 stage IIIa or IIIb AL amyloidosis were randomly assigned to receive anselamimab or placebo with cyclophosphamide, bortezomib, and dexamethasone (with or without daratumumab). The primary end point was a hierarchical composite of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalizations (CVHs), analyzed using the Finkelstein-Schoenfeld test and win ratio estimation.
    RESULTS: Among 406 randomly assigned patients, the primary end point win ratio for anselamimab versus placebo was 1.11 (95% CI, 0.83, 1.50; P = .332) and the hazard ratio (HR) for ACM was 0.80 (95% CI, 0.57, 1.13; P = .290). CVH rates in the anselamimab and placebo groups were 0.59 (95% CI, 0.42, 0.83) and 0.89 (95% CI, 0.55, 1.43), respectively (P = .145). Among patients with kappa isotype (n = 72), the win ratio was 2.06 (95% CI, 0.98, 4.31; P = .100) and anselamimab reduced ACM by 62% versus placebo (HR, 0.38; 95% CI, 0.17 to 0.86; nominal P = .012), and CVH by 71% (IRR, 0.29; 95% CI, 0.10 to 0.87; nominal P = .028) with improvements in Kansas City Cardiomyopathy Questionnaire-Overall Score. There was no clinical benefit observed in the lambda population. Anselamimab was generally well-tolerated; safety data were comparable between treatment arms overall.
    CONCLUSION: Treatment with anselamimab, an antifibril antibody used alongside antiplasma cell dyscrasia therapy, while not meeting the primary end point in the overall population, significantly improved ACM and CVH in patients with kappa AL, potentially offering a new therapeutic option for this isotype.
    DOI:  https://doi.org/10.1200/JCO-26-00755
  18. J Clin Med. 2026 May 11. pii: 3691. [Epub ahead of print]15(10):
    Iron Deficiency and Oral Treatments: Limitations, Pharmacokinetics, and the Role of Iron Protein Succinylate in Clinical Practice.
    José Antonio García-Erce, Santiago García-López, Antonio Martínez-Francés.
      Iron deficiency (ID) is the most prevalent nutritional disorder worldwide, affecting diverse populations including children, women of reproductive age, older adults and patients with chronic conditions. Oral iron supplementation remains the cornerstone of treatment, together with management of the underlying causes. However, conventional ferrous and ferric salts are often associated with gastrointestinal side effects, poor adherence and limited efficacy, especially in inflammatory settings due to hepcidin-mediated absorption blockade. This review summarizes iron absorption physiology, limitations of traditional oral therapies, and the potential benefits of iron protein succinylate (IPS), a ferric complex bound to succinylated casein. IPS provides pH-dependent release and contains succinic acid, which may enhance absorption while reducing gastrointestinal adverse events. Clinical studies indicate that IPS achieves hematologic outcomes comparable or superior to standard oral salts, fewer gastrointestinal effects and better tolerability. These properties make IPS suitable for patients who do not tolerate or respond adequately to conventional therapy. Special attention is given to chronic inflammation, pregnancy, cancer, or gastrointestinal disorders, where oral iron often fails due to impaired absorption or poorer tolerance. Practical recommendations are included to optimize supplementation through dosing strategies and tailored approaches. Overall, IPS offers an effective, better-tolerated alternative to conventional oral iron therapy.
    Keywords:  ID; hepcidin; iron absorption; iron protein succinylate; oral iron supplementation; tolerability
    DOI:  https://doi.org/10.3390/jcm15103691
  19. Blood Adv. 2026 May 27. pii: bloodadvances.2025019057. [Epub ahead of print]
    DUSP1 is a Key Driver of Disease Persistence and Potential Therapeutic Target in Hairy Cell Leukemia.
    Jan-Paul Bohn, Alexandra Scheiber, Gregor Sturm, Thomas Maurer, Anna Mair, Valentina Kugler, Andreas Feichtner, Alexandra Fritz, Omar Torres-Quesada, Ulrich Jaeger, Roland G Huber, Sophia Daum, Agnieszka Martowicz, Norbert Redlinger, Andreas Pircher, Sieghart Sopper, Zlatko Trajanoski, Eduard Stefan, Stefan Salcher, Dominik Wolf.
      Classic hairy cell leukemia (HCL) is a rare indolent B cell lymphoproliferative disorder characterized by the driver mutation BRAF V600E. Standard treatment with purine analogs (i.e. cladribine) induces long-term remissions, but up to 25% of patients relapse early. Even when targeting BRAF V600E, residual HCL cells frequently persist in the bone marrow (BM). To unravel additional biologic alterations contributing to HCL disease persistence, we performed single-cell RNA sequencing in sorted primary HCL cells from long-term versus short-term cladribine responders (LT-R versus ST-R: >10 versus ≤3 years PFS) at diagnosis and in ST-R at diagnosis versus relapses. We identified a distinct HCL subcluster characterized by elevated DUSP1, FOS, and JUND expression, which was detected in all patients and persisted or even expanded at relapses. Cancer pathway analysis suggested enhanced tumor microenvironment dependency as reflected by suppression of the p38-MAP kinase pathway. In the absence of a suitable BRAF V600E-mutated HCL cell line, we validated HAIR-M cells (BRAF D594E) as a bona fide experimental HCL model. The activating BRAF D594E mutation mimics V600E-induced downstream signals that can efficiently be targeted by BRAF inhibitors (BRAFi). HAIR-M co-culture with BM stromal cells (BMSC) strongly induced DUSP1 that was accompanied by protection from BRAFi-induced HAIR-M apoptosis. The functional importance of DUSP1 was corroborated by demonstrating that BMSC-induced protection from cell death could be overcome through DUSP1 inhibition. Our results might set the stage for future clinical testing of DUSP1 inhibition to eliminate minimal residual disease (MRD) and prevent disease relapse in HCL.
    DOI:  https://doi.org/10.1182/bloodadvances.2025019057
  20. Echocardiography. 2026 Jun;43(6): e70517
    A Comprehensive Echocardiographic Assessment of Patients With Chronic Myeloid Leukemia on Dasatinib.
    Chen Chen, Vinesh Appadurai, Maria Paulina Hernandez, Jessica Altman, Nausheen Akhter.
       PURPOSE: Dasatinib, a tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML), is known to cause cardiopulmonary toxicities; however, little is known about the echocardiographic changes associated with this therapy. We present a comprehensive echocardiographic assessment of patients with CML on Dasatinib therapy.
    METHODS: We performed a retrospective cohort analysis on adult patients with CML receiving Dasatinib between 2017 and 2023. Comprehensive clinical and echocardiographic data with speckle-tracking analyses were included.
    RESULTS: Of 199 patients with CML on Dasatinib, 75 (38%) patients had a pre-Dasatinib echocardiogram, and 49 (25%) patients had both pre- and post-Dasatinib echocardiograms. Among 44 patients with analyzable echocardiograms (average age 59 ± 15 years old, 39% female), 7 (16%) patients had baseline heart failure with preserved ejection fraction (HFpEF). After initiation of Dasatinib, there was a significant increase in left ventricular (LV) end-diastolic diameter index (2.4 [2.2, 2.6] vs. 2.6 [2.4, 2.8]cm/m2, p < 0.01), LV end-systolic volume index (16 [13, 26] vs. 21 [14, 26] mL/m2, p = 0.04) and LV mass index (85.3 [75.4, 94.4] vs. 93.1 [80.6, 114.7]g/m2, p < 0.01). There was a significant increase in left atrial (LA) volume index (LAVI, 29.0 ± 10.6 vs. 33.4 ± 13.0 mL/m2, p = 0.01), decrease in lateral e' velocity (11.8 ± 3.3 vs. 10.4 ± 2.8 cm/sec, p < 0.01) and increase in E/e' (9.5 ± 2.8 vs. 10.7 ± 3.5, p = 0.04) post-Dasatinib. Among patients with abnormal LAVI post-Dasatinib, higher LAVI correlated with worsened LA reservoir strain (r = -0.59, p = 0.01). LV ejection fraction and global longitudinal strain were not significantly changed. Patients with baseline HFpEF were significantly more likely to have progression in diastolic dysfunction compared to patients without HFpEF (p = 0.03).
    CONCLUSION: Dasatinib was associated with significant changes in LV structure, LA volume, and diastolic parameters in patients with CML. Patients with baseline HFpEF were more likely to progress in diastolic dysfunction on Dasatinib.
    Keywords:  chronic myeloid leukemia; dasatinib; diastolic dysfunction
    DOI:  https://doi.org/10.1111/echo.70517
  21. Cancers (Basel). 2026 May 07. pii: 1505. [Epub ahead of print]18(10):
    Smoldering Multiple Myeloma: Early Intervention or Structured Surveillance? A Comprehensive Review of Evidence for and Against Early Therapy.
    Kirti Arora, Lara Soueid, Louis Williams, Jahanvi Grover, Diana Basali, Jack Khouri, Yuvraj Kaushal, Sandra Mazzoni, Rockey Dahiya, Beth Faiman, Jason Valent, Faiz Anwer, Shahzad Raza.
      Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by a heterogeneous risk of progression to overt multiple myeloma (MM). Historically managed with active surveillance, advances in risk stratification and the development of novel therapeutics have renewed debate regarding early intervention, particularly in patients with high-risk disease. We conducted a narrative review of clinical trials and observational studies evaluating early treatment versus observation in SMM. Outcomes assessed included progression-free survival (PFS), time to progression (TTP), overall survival (OS), treatment-related toxicity, and quality-of-life measures, alongside evolving diagnostic criteria and risk-stratification models that influence therapeutic decision-making. Early randomized trials using conventional cytotoxic therapy did not demonstrate a survival advantage and supported observation as the standard management approach. However, contemporary studies using novel agents have demonstrated improved disease control in selected high-risk populations. The QuiRedex and ECOG-E3A06 trials showed significant reductions in progression risk with lenalidomide-based therapy, and long-term follow-up suggests a potential overall survival benefit in Qui-Redex. The phase III AQUILA trial further demonstrated delayed progression with daratumumab in high-risk SMM using updated diagnostic criteria. Phase II studies evaluating combination regimens, including KRd-based and daratumumab-containing approaches, have reported high response rates and MRD negativity, although survival data remain immature. Importantly, many benefits reflect delayed biochemical or imaging-defined progression rather than prevention of symptomatic end-organ damage. Current evidence supports selective early intervention in carefully defined high-risk SMM populations; however, uncertainties remain regarding long-term survival benefit, optimal treatment duration, quality-of-life impact, and clonal evolution. Active surveillance with modern monitoring remains appropriate for many patients.
    Keywords:  daratumumab; early intervention; lenalidomide; measurable residual disease; progression-free survival; risk stratification; smoldering multiple myeloma; surveillance
    DOI:  https://doi.org/10.3390/cancers18101505
  22. Blood Adv. 2026 May 26. 10(10): 3744-3745
    Chewing the fat: the role of total cholesterol in MPN management.
    Andrew M Brunner.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2026020072
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