bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–04–12
thirty-six papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Isatuximab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma: a randomized phase 3 trial.
  2. Targeted therapy in early-stage classical Hodgkin lymphoma.
  3. Targeting leukemic stem and progenitor cells expressing different BCR::ABL1 levels: antileukemic activity of asciminib with or without TKIs.
  4. Phase 1/1b study of BCMA-targeting bispecific T-cell engager pavurutamab in relapsed/refractory multiple myeloma.
  5. Advances in first-line treatment for primary central nervous system lymphoma: highlights from the 2025 ASH annual meeting.
  6. Predictors of complete molecular response and impact of allogeneic hematopoietic stem cell transplantation on outcome in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL): results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND).
  7. The Clinical Characteristics and Outcomes of Multiple Myeloma Patients With Oligo or Non-Secretory Relapse-A Retrospective Cohort Study.
  8. Ibrutinib: 10 years and counting.
  9. CPX-351 (Liposomal Cytarabine and Daunorubicin) versus venetoclax plus hypomethylating agent therapy in newly diagnosed acute myeloid leukemia: a retrospective comparison involving 600 Mayo Clinic patients.
  10. Venetoclax-Based Regimens in Chronic Myelomonocytic Leukemia: A Systematic Review and Meta-Analysis.
  11. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma.
  12. A paradigm shift in the treatment of patients with polycythemia vera. The initial early use of recombinant interferon-alpha.
  13. Das not enough in CBF AML.
  14. Leveraging Kinase Drugs for Neurosciences: Discovery of Selective, CNS-Penetrant Reversible Bruton's Tyrosine Kinase Inhibitors as Therapeutics for Neuroinflammation.
  15. Digging deep for the roots of lymphoma.
  16. Ring of fire cells: plasma cell-predominant relapse of Waldenström macroglobulinemia.
  17. HAT-PCR is non-inferior to NGS when quantifying measurable residual disease for myeloma.
  18. Targeted immunoPET imaging of multiple myeloma.
  19. IgD-λ multiple myeloma with hidden light chain on immunofixation electrophoresis: a clinical case.
  20. Epcoritamab plus R² in follicular lymphoma: practice-changing efficacy meets unresolved toxicity trade-offs.
  21. Discovery of potent kinase inhibitors with improved pharmacokinetics and safety potentials through structural optimization of dasatinib.
  22. A pharmacological profile of pacritinib for the treatment of myelofibrosis.
  23. Changes in neutrophil-to-lymphocyte ratio in patients with polycythemia vera treated with ruxolitinib reflect JAK2 variant allele frequency.
  24. Quizartinib in newly diagnosed patients with FLT3-ITD-positive AML who received maintenance therapy in QuANTUM-First.
  25. Efficacy and safety of blinatumomab combination therapy in high-risk B-cell acute lymphoblastic leukemia: A systematic review and meta-analysis.
  26. Response to therapy and prognosis according to molecular characterization in CALR-mutated essential thrombocythemia.
  27. Targeting of ibrutinib resistance-driving pathways by miR-28 in ABC-DLBCL.
  28. Relapse as a return, not a reinvention - genomic stability and pre-existing resistance in mantle cell lymphoma.
  29. Treatment and outcomes of pulmonary mucosa-associated lymphoid tissue lymphoma: A multicenter analysis of 186 patients.
  30. Treatment of Diffuse Large B-Cell Lymphoma.
  31. Targeting BCL-xL in Myeloid Malignancies: From Inhibitors to PROTAC.
  32. Differentiating polycythemia vera from sodium-glucose cotransporter 2 inhibitor-associated polycythemia.
  33. Correction to "Outcomes of patients with relapsed or refractory primary mediastinal B-cell lymphoma treated with anti-CD19 CAR-T cells: CARTHYM, a study from the French national DESCAR-T registry".
  34. Relapse Despite MRD Negativity in Multiple Myeloma: Toward Integrated Risk Prediction.
  35. Concomitant or sequential lower intensity triplet therapy in AML.
  36. Dynamics of BCR::ABL1 transcript levels and clinical outcomes after switch to second-line therapy in pediatric chronic myeloid leukemia.
  1. Nat Med. 2026 Apr 06.
    Isatuximab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma: a randomized phase 3 trial.
    Francesca Gay, Wilfried Roeloffzen, Meletios A Dimopoulos, Laura Rosiñol, Marjolein van der Klift, Roberto Mina, Albert Oriol, Eirini Katodritou, Ka Lung Wu, Paula Rodríguez Otero, Roman Hájek, Elisabetta Antonioli, Mark van Duin, Mattia D'Agostino, Joaquín Martínez-López, Elena M van Leeuwen-Segarceanu, Elena Zamagni, Niels W C J van de Donk, Katja C Weisel, Luděk Pour, Jakub Radocha, Angelo Belotti, Fredrik Schjesvold, Joan Bladé, Hermann Einsele, Pieter Sonneveld, Mario Boccadoro, Annemiek Broijl.
      Induction and consolidation with a quadruplet therapy of a CD38-targeting monoclonal antibody, a proteasome inhibitor, an immunomodulatory drug and dexamethasone are a standard-of-care treatment in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM) with the optimal drugs to be used still under debate. The ongoing, phase 3 EMN24 IsKia trial randomized 302 TE patients with NDMM aged ≤70 years 1:1 to isatuximab-carfilzomib-lenalidomide-dexamethasone (Isa-KRd) versus KRd pretransplant induction and post-transplant consolidation. The primary endpoint was the rate of measurable residual disease (MRD) negativity (sensitivity of 10-5 or better) by next-generation sequencing (NGS) after consolidation. Key secondary endpoints were the rates of NGS-MRD negativity after induction and progression-free survival (PFS). MRD negativity rates at higher sensitivity (10-6 or better) were exploratory. Post-consolidation MRD negativity was significantly higher with Isa-KRd versus KRd at the 10-5 (77% versus 67%; odds ratio (OR) 1.67, P = 0.049) and 10-6 (68% versus 48%; OR 2.36, P = 0.0004) sensitivities. Deep MRD responses were rapid (post-induction Isa-KRd versus KRd: 10-5 46% versus 27%, OR 2.32, P = 0.0007; 10-6 28% versus 14%, OR 2.44, P = 0.0029) and durable (1-year sustained 10-6 MRD negativity 52% versus 38%, OR 1.82, P = 0.012). At current follow-up, PFS data were immature. Grade 3-4 non-hematologic adverse events (AEs), treatment discontinuations and deaths due to AEs were similar in the two arms. Isa-KRd significantly improved NGS-MRD negativity in TE patients with NDMM, with a manageable safety profile. ClinicalTrials.gov registration: NCT04483739 .
    DOI:  https://doi.org/10.1038/s41591-026-04282-0
  2. Blood. 2026 Apr 09. 147(15): 1655-1657
    Targeted therapy in early-stage classical Hodgkin lymphoma.
    Tomohiro Aoki, John Kuruvilla.
      
    DOI:  https://doi.org/10.1182/blood.2025032560
  3. Front Pharmacol. 2026 ;17 1780054
    Targeting leukemic stem and progenitor cells expressing different BCR::ABL1 levels: antileukemic activity of asciminib with or without TKIs.
    Michele Massimino, Elena Tirrò, Chiara Romano, Stefania Stella, Cristina Tomarchio, Silvia Rita Vitale, Livia Manzella, Francesco Di Raimondo, Fabio Stagno, Paolo Vigneri.
      Tyrosine kinase inhibitors (TKIs) targeting ABL1 catalytic activity have markedly improved Chronic Myeloid Leukemia (CML) outcomes, inducing unprecedented and durable therapeutic responses. However, while TKIs efficiently target committed leukemic progenitors, they fail to eradicate leukemic stem cells (LSCs), which may drive disease relapse. High BCR::ABL1 transcripts at diagnosis confer a proliferative and survival advantage and are associated with a higher risk of CML progression to the acute phase. Specifically Targeting the ABL Myristoyl Pocket (STAMP) compounds, including asciminib (ASC), provide a novel mechanism to inhibit BCR::ABL1 catalytic activity. ASC is FDA-approved for patients who have failed one or more TKIs, and its efficacy has been evaluated as monotherapy, and in combination with different TKIs, in T315I-positive or advanced-phase CML. We investigated the cytotoxic effects of ASC, alone or with imatinib (IM) or nilotinib (NIL), on committed progenitors and LSCs from CML patients expressing high or low BCR::ABL1 at diagnosis. ASC reduced BCR::ABL1-dependent survival and impaired clonogenicity in committed progenitors with low, but not high, BCR::ABL1 transcripts. ASC also disrupted LSC self-renewal, reducing both frequency and number of Long-Term Culture-Initiating Cells (LTC-ICs). When combined with IM or NIL, ASC restored TKI activity against LTC-ICs expressing high BCR::ABL1 transcripts, with the association of ASC and NIL reducing both LTC-IC division rates and LTC-IC-derived CFUs. These findings suggest that ASC, alone or with NIL, may target LSCs and improve outcomes in patients with high BCR::ABL1 expression at diagnosis.
    Keywords:  BCR::ABL1; LTC-ICs; TKIs; asciminib; leukemic stem cells
    DOI:  https://doi.org/10.3389/fphar.2026.1780054
  4. Blood. 2026 Apr 08. pii: blood.2025032044. [Epub ahead of print]
    Phase 1/1b study of BCMA-targeting bispecific T-cell engager pavurutamab in relapsed/refractory multiple myeloma.
    Hans C Lee, Wouter J Plattel, Simon J Harrison, Douglas W Sborov, Suzanne Lentzsch, Andrew Spencer, Ruben Niesvizky, Suzanne Trudel, Peter Mollee, Ravi Vij, Monique C Minnema, Leo Rasche, Vijay V Upreti, Di Zhou, Qing Xia, Mihaela Talpes, Tobias Eggert, Prashant Kapoor, Sikander Ailawadhi.
      The B-cell maturation antigen (BCMA)-targeting bispecific T-cell engager (BiTE®) pavurutamab (AMG 701) directs the cytotoxic T-cell response toward multiple myeloma (MM) cells. This phase 1/1b, open-label, dose-exploration and dose-expansion study evaluated the safety, tolerability, and efficacy of pavurutamab monotherapy in patients with triple-class relapsed/refractory MM (RRMM). Pavurutamab (5-18,000 µg) was administered intravenously weekly with step-up dosing in week 1. Overall, 172 patients received at least one dose of pavurutamab; 73 received the recommended phase 2 dose (RP2D; 18,000 µg), with two different step-up dosing regimens in phase 1b. Twelve patients had dose-limiting toxicities, which included cytokine release syndrome (CRS) and increased transaminases. None occurred at the RP2D. The most frequently reported treatment-emergent adverse events included CRS (74.4%), anemia (61.0%), neutropenia (47.1%), and hypophosphatemia (45.3%). Grade 3 or higher infections were noted in 60 patients (34.9%). The overall response rate was 46.5% among all patients and 65.8% (≥very good partial response [VGPR], 60.3%) among 73 patients treated at the RP2D. At median follow-up of 17.2 months, median duration of response was 36.6 months (95% confidence interval [CI]: 22.3-not estimable). Median progression-free survival for all patients was 5.5 months (95% CI: 2.8-10.1) and 16.8 months (95% CI: 5.0-not estimable) with the RP2D. Pavurutamab exposure generally increased in a dose-proportional manner, with high soluble BCMA levels correlating with lower exposure level. The acceptable safety profile, pharmacokinetics, and preliminary efficacy of pavurutamab supports anti-BCMA T-cell engager therapy in heavily pretreated patients with RRMM. The trial was registered at www.ClinicalTrials.gov as # NCT03287908.
    DOI:  https://doi.org/10.1182/blood.2025032044
  5. J Hematol Oncol. 2026 Apr 09. pii: 22. [Epub ahead of print]19(1):
    Advances in first-line treatment for primary central nervous system lymphoma: highlights from the 2025 ASH annual meeting.
    Rong Wei, Shenmiao Yang.
      Advances in targeted therapies for newly diagnosed primary central nervous system lymphoma (PCNSL) were a key highlight at the 2025 ASH Annual Meeting. While high-dose methotrexate (HD-MTX) remains the cornerstone of PCNSL treatment, the integration of BTK inhibitors, immunomodulators, and novel agents-such as selinexor and anti-PD-1 antibodies-is reshaping the first-line management paradigm. These emerging combinations are improving response rates and survival, paving the way for more effective strategies. Here, we provide a timely synthesis of these pivotal updates presented at ASH 2025.
    Keywords:  Anti-PD1 antibody; BTK inhibitor; Immunomodulator; PCNSL; Selinexor
    DOI:  https://doi.org/10.1186/s13045-026-01786-7
  6. Leuk Lymphoma. 2026 Apr 09. 1-8
    Predictors of complete molecular response and impact of allogeneic hematopoietic stem cell transplantation on outcome in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL): results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND).
    Razan Mohty, Ravi Narra, Alice S Mims, Cameron Hunter, Rory M Shallis, Vamsi Kota, Omer Jamy, Alexander Coltoff, Tamer Adel Othman, Brian A Jonas, Anand A Patel, Adam S DuVall, Charles E Foucar, Mahmoud Abdelsamia, Neil Palmisiano, Shyam A Patel, Emily Curran, Zulfa Omer, Anjali Advani, Ehab Atallah, Mark R Litzow, Talha Badar.
      With the advent of tyrosine kinase inhibitors (TKIs), the outcomes of patients with Philadelphia positive acute lymphoblastic leukemia (Ph + ALL) improved. We conducted a retrospective multicenter study of 467 adult patients with Ph + ALL (2003-2023) evaluating predictors of complete molecular response (CMR) at 3 months and its impact on outcomes. CMR was achieved in 297(63.7%) patients. In the multivariate analysis, WBC > 70,000/L at diagnosis (p = 0.01), p210 BCR::ABL1 fusion (p < 0.001) and monosomy 7 (p = 0.007) were independently associated with failure to achieve CMR, while use of ponatinib or dasatinib (p = 0.008) and intensive chemotherapy (IC) (p = 0.009) predicted higher CMR. Among patients who achieved CMR, the median relapse-free survival (RFS) was significantly better (123.1 vs. 30.3 months, p < 0.0001), however, overall survival (OS) was not significantly different (129.2. vs. 149.3 months, p = 0.07) with or without allogeneic hematopoietic cell transplantation (allo-HCT). These findings suggest that allo-HCT may be deferred in selected patients achieving early CMR, although prospective validation is needed.
    Keywords:  Philadelphia positive ALL; complete metabolic response; tyrosine kinase inhibitors
    DOI:  https://doi.org/10.1080/10428194.2026.2650679
  7. Hematol Oncol. 2026 May;44(3): e70192
    The Clinical Characteristics and Outcomes of Multiple Myeloma Patients With Oligo or Non-Secretory Relapse-A Retrospective Cohort Study.
    Iuliana Vaxman, Itai Zamir, Inbar Cohen, Gil Fridberg, Tamir Shragai, Svetlana Trestman, Tomer Ziv Baran, Efrat Luttwak, Ronit Shmuel, Natan Melamed, Shai Levy, Irit Avivi, Pia Raanani, Angela Dispenzieri, Morie A Gertz, Yael C Cohen.
      Oligo-secretory and non-secretory MM present a clinical challenge due to the difficulties in initial diagnosis, response to treatment assessment, and relapse detection. They are excluded from most clinical trials, which typically require measurable disease. We describe the characteristics and outcomes of 86 patients with secretory myeloma at diagnosis who developed an OSR, matched 1:1 to a cohort with secretory relapse (SR). With a median follow-up of 9.3 years, 16.6% (48/289) of evaluable patients developed an OSR. Lower levels of light chains at presentation, and younger age are predictive of an OSR. The median OS since relapse of the OSR group was 4.01 (95% CI 1.625-6.395) versus 3.25 (95% CI 2.255-4.245) years in the SR control group (p = 0.4). A third of our OSR cohort had a subsequent SR. We did not find any predictive factor for SR after OSR. The median OS of the subgroup of patients who developed a SR after OSR was 3.35 years (95% CI 1.541-5.159), versus 5.8 years (95% CI 2.072-9.528) in the group that remained oligo-secretory (p = 0.336). The median TTNT of the SR after OSR group was 1.68 years (95% CI 0.341-0.919) versus 4.58 (95% CI not reached-not reached) in the group that remained oligo-secretory (p < 0.001).
    Keywords:  multiple myeloma relapse; non‐secretory multiple myeloma; oligo‐secretory multiple myeloma
    DOI:  https://doi.org/10.1002/hon.70192
  8. Blood. 2026 Apr 09. 147(15): 1653-1654
    Ibrutinib: 10 years and counting.
    Jennifer R Brown.
      
    DOI:  https://doi.org/10.1182/blood.2025032468
  9. Blood Cancer J. 2026 Apr 06.
    CPX-351 (Liposomal Cytarabine and Daunorubicin) versus venetoclax plus hypomethylating agent therapy in newly diagnosed acute myeloid leukemia: a retrospective comparison involving 600 Mayo Clinic patients.
    Saubia Fathima, Lior Rokach, Nour Ghosoun, Mahsa Rezasoltani, Rimal Ilyas, Ali Alsugair, Kristen McCullough, Maymona Abdelmagid, Aref Al-Kali, Hassan B Alkhateeb, Kebede H Begna, Abhishek A Mangaonkar, Aasiya Matin, Antoine N Saliba, Mehrdad Hefazi Torghabeh, Mark R Litzow, William Hogan, Mithun Shah, Mrinal M Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Nathan Punwani, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Ayalew Tefferi, Naseema Gangat.
      The comparative value of liposomal cytarabine/daunorubicin (CPX-351) versus venetoclax plus a hypomethylating agent (Ven-HMA) in the frontline treatment of older adults with primary (de novo) or secondary acute myeloid leukemia (AML) remains uncertain. In the current study, we retrospectively examined outcomes of 600 patients with newly diagnosed AML treated with CPX-351 (N = 112) or Ven-HMA (N = 488). AML subtypes included de novo (N = 277, 46%), post-myelodysplastic syndrome (post-MDS, N = 114,19%), post-myeloproliferative neoplasm (post-MPN, N = 70, 12%), post-MDS/MPN (N = 36, 6%), and t-AML (N = 103, 17%). Patients receiving CPX-351 were younger (median 65 vs. 73 years; p < 0.01), predominantly female (50% vs. 38%; p = 0.02), more likely to have secondary AML (68% vs. 51%; p < 0.01), and less likely to harbor NPM1MUT (5% vs. 12%; p = 0.02). Rates of complete response with or without count recovery (CR/CRi) were comparable between CPX-351 and Ven-HMA (55% vs. 60%; p = 0.30), including AML with myelodysplasia-related gene mutations or cytogenetic abnormalities (AML-MR 60% vs. 63%; p = 0.70). Ven-HMA use was associated with fewer infectious complications (62% vs. 83%; p < 0.01) and yielded higher CR/CRi rates in males (60% vs. 45%; p = 0.04), de novo AML (68% vs. 50%; p = 0.03), and in the presence of STAG2MUT (86% vs. 44%; p = 0.02), or CEBPAMUT (88% vs. 50%; p = 0.03). Overall survival censored for transplant, was similar (median 10 vs. 13 months; p = 0.90), with Ven-HMA being superior in post-MDS AML (median 12 vs. 7 months; p = 0.02) and CPX-351 in the presence of SF3B1MUT (median not reached vs. 14 months; p < 0.01). Our findings suggest that Ven-HMA is as effective and less toxic than CPX-351 in newly diagnosed AML, including AML-MR, despite selection of younger, fitter patients for CPX-351.
    DOI:  https://doi.org/10.1038/s41408-026-01495-x
  10. Acta Haematol. 2026 Apr 07. 1-25
    Venetoclax-Based Regimens in Chronic Myelomonocytic Leukemia: A Systematic Review and Meta-Analysis.
    Mohammed Abdulgayoom, Mohammad S Afana, Leen Haj Saleh, Aadhila Abbas Manthiri, Noor Adel Aweer, Mohammad Bakheet, Abdulrahman F Al-Mashdali, Shehab F Mohamed.
      Chronic myelomonocytic leukemia (CMML) is a biologically heterogeneous myelodysplastic/myeloproliferative neoplasm with limited disease-modifying options beyond hypomethylating agents (HMAs) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Venetoclax (VEN), a selective BCL-2 inhibitor, is increasingly used off-label in CMML, yet CMML-specific efficacy and safety remain incompletely defined. We conducted a systematic review and meta-analysis in accordance with PRISMA 2020, including adult CMML cohorts receiving VEN-based therapy with extractable CMML-specific outcomes. Seventeen publications representing nine unique studies were included, comprising 145 VEN-treated CMML patients. Most regimens combined VEN with azacitidine, decitabine, or oral decitabine-cedazuridine, using heterogeneous dosing schedules with CYP3A-guided dose modifications. Responses occurred early, typically within one to two treatment cycles, but durability was modest. Random-effects meta-analysis yielded pooled complete remission (CR) rates of 19.1% (95% CI, 9.4-34.9; I²=55%), marrow CR (mCR) rates of 36.4% (95% CI, 24.7-50.0; I²=21%), and an overall response rate (ORR) of 71.9% (95% CI, 56.5-83.4; I²=56%). VEN-based therapy was associated with substantial myelosuppression, including frequent grade ≥3 neutropenia and thrombocytopenia, with clinically relevant infectious complications; early mortality was low. In summary, VEN-based regimens demonstrate measurable but limited activity in CMML, with high ORR, but low CR rates. Prospective CMML-specific trials are needed to define optimal use and patient selection.
    DOI:  https://doi.org/10.1159/000551885
  11. N Engl J Med. 2026 Apr 09. 394(14): 1456
    Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma.
      
    DOI:  https://doi.org/10.1056/NEJMx250006
  12. Leukemia. 2026 Apr 08.
    A paradigm shift in the treatment of patients with polycythemia vera. The initial early use of recombinant interferon-alpha.
    Richard T Silver, Hans Carl Hasselbalch.
      During the past 35 years, single-arm studies documented the efficacy and safety of recombinant interferon alpha (rIFNα) for treating polycythemia vera (PV). In some patients, 2-5 years of disease-modifying treatment resulted in symptom relief, regression of splenomegaly, normalization of abnormal blood counts and marrow morphology, and sustained JAK2V617F molecular remission. The PROUD-CONTI study showed the superiority of rIFNα compared to hydroxyurea (HU), which led to the European Medicines Agency approval in 2019 of ropeginterferon alpha-2b ("ropegIFN") for ELN-defined high-risk PV patients. In 2021, the Food and Drug Administration (USA) gave unrestricted approval, except for pregnant PV patients. The Low-PV randomized trial established the superiority of ropegIFN compared to phlebotomy-only (PHLEB-O) in ELN-defined low-risk patients. Nevertheless, worldwide, HU remains the cytoreductive drug most often used; maintenance PHLEB-O is still endorsed as maintenance therapy by some hematologists. The National Comprehensive Cancer Network (NCCN, USA) approved ropegIFN as a II-A recommendation for ELN-defined low and high-risk disease; the ELN suggested criteria for using rIFNα in low-risk patients if certain issues developed after PHLEB-O, including more symptoms, progressive splenomegaly, significant leukocytosis, thrombocytosis, or inadequate hematocrit control. These issues are important because even low-risk patients are at increased thrombotic risk, estimated at 2 to 3 times that of the general population. Moreover, as PV progresses, the development of myelofibrosis is the leading cause of morbidity, perhaps abetted by PHLEB-O. Here, we review recent progress in the treatment of PV with rIFNα and discuss our rationales and perspectives for, and the endorsement of the initial treatment with rIFNα of both low and high-risk PV patients, unless a contraindication exists to its use.
    DOI:  https://doi.org/10.1038/s41375-026-02882-w
  13. Blood. 2026 Apr 09. 147(15): 1658-1659
    Das not enough in CBF AML.
    Richard M Stone.
      
    DOI:  https://doi.org/10.1182/blood.2025032734
  14. J Med Chem. 2026 Apr 07.
    Leveraging Kinase Drugs for Neurosciences: Discovery of Selective, CNS-Penetrant Reversible Bruton's Tyrosine Kinase Inhibitors as Therapeutics for Neuroinflammation.
    Brian T Hopkins, Isaac E Marx, Harlod George Vandeveer, Marta Nevalainen, Rebecca Basile, Bekim Bajrami, Colin K Choi, Richard J Grater, Chungang Gu, Marc Hoemberger, Ekta Kadakia, Sudarshan K Kapadnis, Ying Liu, Bin Ma, Tom Magee, Claire M Metrick, Michael Mingueneau, Cathy A Muste, Chelsea R Parker Harp, Robin J Prince, Joseph C Santoro, Jurgen Schulz, Simone Sciabola, Hao Tang, Ti Wang, Robert Meissner, Tonika Bohnert.
      Bruton's tyrosine kinase (BTK) is a nonreceptor tyrosine kinase clinically validated to impact B-cell development. Molecules designed to target BTK, through either covalent or reversible inhibition, have transformed the treatment of hematopoietic malignancies. Wen, T.; Wang, J.; Shi, Y.; Qian, H.; Liu, P. Inhibitors targeting Bruton's tyrosine kinase in cancers: drug development advances. Leukemia 2021, 35(2), 312-332.10.1038/s41375-020-01072-6. These advancements are paving the way for new therapeutics to treat nononcology indications, De Bondt, M.; Renders, J.; Struyf, S.; Hellings, N. Inhibitors of Bruton's tyrosine kinase as emerging therapeutic strategy in autoimmune diseases. Autoimmun. Rev. 2024, 23(5), 103532.10.1016/j.autrev.2024.103532 such as multiple sclerosis (MS), and provide benefits to patients with progressive disease. In this context, we describe the discovery of a highly selective, CNS-penetrant, reversible BTK inhibitor designed to sequester Tyr-551, the critical phosphorylation site, into an inactive conformation, thereby blocking B-cell receptor (BCR) signaling. While this class of molecules demonstrated excellent safety when administered at doses that fully inhibited B-cell activity in the periphery, increasing exposure to achieve similar efficacy in the CNS led to adverse findings. This raises the question of whether it was a molecule-specific off-target toxicity or a consequence of blocking BTK function in microglia.
    DOI:  https://doi.org/10.1021/acs.jmedchem.5c02648
  15. Blood. 2026 Apr 09. 147(15): 1657-1658
    Digging deep for the roots of lymphoma.
    Joseph G Schroers-Martin.
      
    DOI:  https://doi.org/10.1182/blood.2025032718
  16. Blood. 2026 Apr 09. 147(15): 1779
    Ring of fire cells: plasma cell-predominant relapse of Waldenström macroglobulinemia.
    Pedro Perez, Alex Freire Sandes.
      
    DOI:  https://doi.org/10.1182/blood.2025031678
  17. Br J Haematol. 2026 Apr 08.
    HAT-PCR is non-inferior to NGS when quantifying measurable residual disease for myeloma.
    Elizabeth Hughes, Piers Blombery, Sushmitha Kannan, Tiffany Khong, Andrew Spencer, Alexander Morley.
      
    Keywords:  MRD; NGS; PCR; hypermutation; myeloma
    DOI:  https://doi.org/10.1111/bjh.70478
  18. Semin Hematol. 2026 Mar 14. pii: S0037-1963(26)00018-1. [Epub ahead of print]
    Targeted immunoPET imaging of multiple myeloma.
    Gary A Ulaner, Ola Landgren.
      Current standard of care methods of imaging multiple myeloma disease burden are suboptimal. For example, fluorodeoxyglucose-(FDG)-PET/CT may fail to detect up to 50% of myeloma lesions. Immunologically based positron emission tomography (immunoPET) is an imaging modality allowing detecting of multiple myeloma by targeting specific tumor antigens using antibodies, antibody fragments, or antibody mimics labelled with position emitting radioisotopes. ImmunoPET agents for multiple myeloma have targeted CD38, CD46, CD138, BCMA, CS1, VLA-4, and CXCR4, which are all highly expressed on the majority of myeloma cells. As opposed to biopsies, immunoPET allows noninvasive, whole-body assessment of multiple myeloma tumor burden. Clinical applications of immunoPET for patients with multiple myeloma currently under investigation include disease detection, localization, quantification, biopsy targeting, and evaluation of residual disease following therapy. In addition, targeted immunoPET is under investigation for its ability to predict response to subsequent targeting therapies. For instance, immunoPET agents targeting CD38 are being used to predict response to subsequent CD38-targeted therapies using uptake on pretherapy immunoPET studies as a predictive biomarker. When the positron emitting radioisotope can be exchanged for an isotope emitting a high energy beta or alpha particle, the construct may be utilized for radioligand therapy of multiple myeloma. This review introduces the concept of immunoPET, summarizes the current immunoPET agents in development, and discusses potential clinical applications of immunoPET agents.
    Keywords:  BCMA; CD38; CD46; CXCR4; ImmunoPET; Multiple myeloma
    DOI:  https://doi.org/10.1053/j.seminhematol.2026.03.005
  19. Clin Chem Lab Med. 2026 Apr 13.
    IgD-λ multiple myeloma with hidden light chain on immunofixation electrophoresis: a clinical case.
    Xiao Hu, Minyi Wu, Fengmei Su, Haiyang Yang, Xinxin Wan, Hongyan Tong, Yu Chen.
      
    Keywords:  capillary electrophoresis immunotyping; hidden light chain; immunofixation electrophoresis; immunoglobulin D; multiple myeloma; serum free light chain assay
    DOI:  https://doi.org/10.1515/cclm-2026-0250
  20. Front Oncol. 2026 ;16 1811781
    Epcoritamab plus R² in follicular lymphoma: practice-changing efficacy meets unresolved toxicity trade-offs.
    Qinghua Ke, Shiqiong Zhou.
      
    Keywords:  R² regimen; bispecific antibody; epcoritamab; follicular lymphoma; infection risk; toxicity
    DOI:  https://doi.org/10.3389/fonc.2026.1811781
  21. Commun Med (Lond). 2026 Apr 10.
    Discovery of potent kinase inhibitors with improved pharmacokinetics and safety potentials through structural optimization of dasatinib.
    Kan He, Lining Cai.
       BACKGROUND: Dasatinib exhibits broad therapeutic potentials for several diseases; however, its clinical application is limited by safety concerns and unfavorable pharmacokinetics.
    METHODS: Structural optimization of dasatinib yielded PDD-87. Preclinical studies evaluated kinase inhibition, antiproliferative activity in leukemia and lymphoma cell lines, antitumor effects in a xenograft model, pharmacokinetics and metabolism in vitro and in rodents, and exploratory safety in mice.
    RESULTS: Here we show that PDD-87 strongly inhibits ABL and BTK along with their key mutants, and SRC family kinases (IC₅₀ <1 nM), displaying potent antiproliferative effects against several leukemia and lymphoma cell lines. In a K-562G mouse xenograft model, PDD-87 significantly reduces tumor growth in a dose-dependent manner. Compared to dasatinib, PDD-87 exhibits lower clearance (405 vs 989 mL/hr/kg), reduced volume of distribution (0.9 vs 2.4 mL/hr/kg), higher plasma exposure (2521 vs 190 hr*pmol/mL for oral dose), and improved oral bioavailability (18.9 vs 3.9%) in rats. PDD-87 demonstrates lower metabolic clearance than dasatinib in human, mouse, rat, and dog liver microsomes. Metabolically, PDD-87 undergoes hydroxylation on the 2-chloro-6-methylphenyl ring, followed by sulfation, and glucuronidation. Significantly, PDD-87 shows markedly lower lung accumulation than dasatinib, suggesting a reduced risk of pulmonary toxicity. The lung/plasma ratios of Cmax and AUClast for PDD-87 are 2 and 4, respectively, compared to 12 and 22 for dasatinib. Additionally, PDD-87 is well-tolerated in mice at doses up to 200 mg/day for two weeks, with no overt toxicity.
    CONCLUSIONS: PDD-87 is a highly potent, selective kinase inhibitor with improved pharmacokinetics and safety potentials, holding promise for broader clinical applications.
    DOI:  https://doi.org/10.1038/s43856-026-01550-5
  22. Expert Rev Clin Pharmacol. 2026 Apr 08.
    A pharmacological profile of pacritinib for the treatment of myelofibrosis.
    Hannah Goulart, Lucia Masarova, Naveen Pemmaraju, Prithviraj Bose.
       INTRODUCTION: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, progressive cytopenias, and limited overall survival. While Janus kinase (JAK) inhibitors have transformed symptom- and spleen-directed management, many patients, particularly those with baseline thrombocytopenia, historically had limited therapeutic options due to treatment-related myelosuppression and exclusion from pivotal trials. Pacritinib was developed to address this unmet need through selective JAK2, ACVR1, and IRAK1 inhibition with relative sparing of JAK1.
    AREAS COVERED: This review summarizes the pharmacologic properties, preclinical rationale, and clinical development of pacritinib for the treatment of MF. We discuss early-phase studies, pivotal phase III trials, dose-optimization efforts, and post-approval real-world data, with particular emphasis on patients with severe thrombocytopenia.
    EXPERT OPINION: Pacritinib occupies a distinct niche within the MF treatment landscape, offering meaningful spleen and symptom benefit in patients with severe thrombocytopenia who historically lacked effective therapeutic options. While no JAK inhibitor has demonstrated clear disease-modifying effects in MF, pacritinib's non-myelosuppressive profile, unique activity against IRAK1, and potential anemia benefit via ACVR1 inhibition suggests potential utility as a backbone for future combination strategies. Ongoing and future studies will be critical to further define its role in phenotype-driven MF management.
    Keywords:  JAK-inhibitor; Myelofibrosis; myeloproliferative neoplasm; pacritinib; thrombocytopenia
    DOI:  https://doi.org/10.1080/17512433.2026.2657856
  23. Haematologica. 2026 Apr 09.
    Changes in neutrophil-to-lymphocyte ratio in patients with polycythemia vera treated with ruxolitinib reflect JAK2 variant allele frequency.
    Paola Guglielmelli, Chiara Paoli, Giulia Borgi, Lorenzo Fagiolo, Sara Bianchini, Giuseppe Gaetano Loscocco, Francesca Gesullo, Fernanda Di Vaio, Cecilia Matteoli, Fabiana Pancani, Sofia Danesi, Simona Pestelli, Tiziano Barbui, Alessandro M Vannucchi.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2025.300245
  24. Blood Adv. 2026 Apr 08. pii: bloodadvances.2025017738. [Epub ahead of print]
    Quizartinib in newly diagnosed patients with FLT3-ITD-positive AML who received maintenance therapy in QuANTUM-First.
    Mark J Levis, Harry P Erba, Pau Montesinos, Elzbieta Patkowska, Jorge E Cortes, Alexander E Perl, Hervé Dombret, Sergio Amadori, Jianxiang Wang, Richard F Schlenk, Li Liu, Yasser Mostafa Kamel, Karima Imadalou, Abderrahmane Laadem, Kristy Burns, Mikkael A Sekeres.
      QuANTUM-First (NCT02668653) demonstrated improved overall survival (OS) in FLT3-ITD-positive patients with newly diagnosed acute myeloid leukemia (ndAML) treated with quizartinib plus standard chemotherapy. Herein, we evaluated the impact of post-consolidation/post-transplant single-agent maintenance therapy on clinical outcomes in patients receiving maintenance, focusing on measurable residual disease (MRD) status at maintenance onset. Overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were prespecified exploratory analyses. Cumulative incidence of relapse (CIR), analyses by allogeneic hematopoietic stem cell transplant (allo-HCT), and analyses by MRD status were post-hoc and not powered for statistical significance. Samples for FLT3-ITD MRD analysis were collected in composite complete remission patients ≤30 days before receiving maintenance and assessed by an ultrasensitive amplicon-based assay. More transplanted quizartinib-treated patients received maintenance (71%) vs placebo (55%); OS benefit was not demonstrated among these patients. In patients who did not undergo allo-HCT, quizartinib maintenance was associated with a significant OS benefit (HR 0.401; 95% CI, 0.192-0.838), including a benefit in patients who were MRD-negative at the start of maintenance (OS HR of 0.194, 95% CI, 0.056-0.676). Patients who were MRD-negative at the completion of consolidation achieved 89.1% (95% CI, 70.0%-96.4%) survival at 3 years with quizartinib maintenance in the absence of allo-HCT. These data suggest that for patients who achieve FLT3-ITD MRD negativity after induction and consolidation with quizartinib, maintenance with quizartinib provides a significant survival benefit and in some patients may eliminate the need for allo-HCT.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017738
  25. Oncol Lett. 2026 May;31(5): 197
    Efficacy and safety of blinatumomab combination therapy in high-risk B-cell acute lymphoblastic leukemia: A systematic review and meta-analysis.
    Mei Wang, Xinlin Yu, Zhongqing Zou, Yan He, Lvlin Chen, Ying Lan.
      The present study aimed to evaluate the efficacy and safety of blinatumomab-based combination therapy for high-risk B-cell acute lymphoblastic leukemia (B-ALL). PubMed, Embase, Web of Science and the Cochrane Library were searched for clinical studies on blinatumomab. The primary endpoints were complete remission (CR), minimal residual disease (MRD) and complete molecular remission (CMR). The secondary endpoint was overall survival (OS). Safety outcomes included adverse events (AEs), cytokine release syndrome, neurological events and hematological toxicity. A total of 11 studies involving 402 patients were included. The pooled CR rate was 87% (95% CI, 78-95%), the MRD negativity rate was 81% (95% CI, 75-87%) and the CMR rate was 81% (95% CI, 69-92%). The 1-year OS rate was 91% (95% CI, 78-100%), the 2-year OS rate was 87% (95% CI, 71-100%) and the 3-year OS rate was 52% (95% CI, 36-66%). Regarding safety, 86% (95% CI, 77-96%) of patients experienced all-grade AEs. Grade ≥3 AEs were generally consistent with known safety profiles, with the most common events being neutropenia (38%; 95% CI, 0-84%), febrile neutropenia (26%; 95% CI, 10-43%), and hyperglycemia (21%; 95% CI, 5-36%). In conclusion, blinatumomab-based combination therapy is an effective treatment for high-risk B-ALL with manageable toxicity.
    Keywords:  acute lymphoblastic leukemia; adverse events; blinatumomab; efficacy
    DOI:  https://doi.org/10.3892/ol.2026.15552
  26. Hemasphere. 2026 Mar;10(3): e70325
    Response to therapy and prognosis according to molecular characterization in CALR-mutated essential thrombocythemia.
    Marta Santaliestra, Marta Garrote, María Concepción Fernández-Rodríguez, Patricia Vélez, Alicia Senín, Eduardo Arellano-Rodrigo, Neus Garcia-Gisbert, Raquel Longarón, Manuel Pérez-Encinas, Gonzalo Caballero-Navarro, Maria Soledad Noya-Pereira, Beatriz Cuevas, María Teresa Gómez-Casares, Ruth Stuckey, Gonzalo Carreño-Tarragona, Francisca Ferrer-Marin, Miguel Angel Cortés, Elena Magro, Isabel Mata, Anna Angona, Raúl Pérez, María Laura Fox, Irene Pastor-Galán, Paula Sastre, Ana Triguero, Valentín García-Gutierrez, Juan Carlos Hernández-Boluda, Beatriz Bellosillo, Alberto Alvarez-Larran.
      Response to cytoreductive therapy according to CALR mutation type, CALR variant allele frequency (VAF), and additional mutations has not been previously studied in essential thrombocythemia (ET). The impact of the molecular profile on treatment response and the main clinical outcomes was analyzed in 557 CALR ET patients (CALR Type 1, n = 339, median VAF 36%; and CALR Type 2, n = 218, median VAF 35%). NGS data on additional mutations were available for 257 patients. CALR Type 2 showed a significantly higher rate of complete hematological response (CHR) to first-line cytoreduction. However, in the multivariate analysis, the effect of CALR mutation type in response rates was no longer significant once CALR VAF was considered, whereas high VAF remained independently associated with a lower likelihood of achieving CHR (hazard ratio [HR] = 0.482, 95% confidence interval (CI): 0.297-0.781; P = 0.003). Moreover, high VAF was also associated with an increased risk of arterial thrombosis (HR = 4.135, 95% CI: 1.093-15.645; P = 0.037), and progression to MF (HR = 2.631, 95% CI: 1.004-6.890; P = 0.049). Although allele burden affects overall survival (OS) in the entire population, its impact was surpassed by the presence of high molecular risk (HMR) mutations (HR = 2.114, 95% CI: 1.070-4.176; P = 0.031). Furthermore, the HMR profile was also associated with a higher risk of progression to acute leukemia, while it did not influence the probability of CHR or progression to MF. In conclusion, CALR VAF and HMR profile appear to be more important than CALR mutation type regarding treatment response and major clinical outcomes in ET.
    DOI:  https://doi.org/10.1002/hem3.70325
  27. Leukemia. 2026 Apr 08.
    Targeting of ibrutinib resistance-driving pathways by miR-28 in ABC-DLBCL.
    Emigdio Álvarez-Corrales, Rocío Moreno-Palomares, Carmen Gómez-Escolar, Mario Martínez, Udane Moral-Pérez, María Laguna-Herrero, Teresa Fuertes, Belén S Estrada, Sonia Mur, Adriana de Bonis, Magdalena Leiva, Nuria Martínez-Martín, Álvaro Somoza, Almudena R Ramiro, Virginia G de Yébenes.
      Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell lymphoma. Although many patients respond well to R-CHOP immunochemotherapy, those with the activated B-cell (ABC) subtype are often refractory or relapse. Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib have improved outcomes, but acquired resistance limits their long-term efficacy. Here, we modeled the development of ibrutinib resistance in ABC-DLBCL and investigated whether the BCR-signaling regulator microRNA-28 (miR-28) can block this process. Using flow cytometry-based competition assays, multicolor clonal barcoding, transcriptomic profiling, and xenograft models, we found that miR-28 expression impairs the emergence of ibrutinib-resistant ABC-DLBCL cells. Mechanistically, miR-28 interferes with the clonal selection process triggered by ibrutinib treatment and rewires transcriptional programs by downregulating mitochondrial and mTOR signaling pathways critical for resistance development. Furthermore, the miR-28-repressed gene signature associated with ibrutinib resistance correlates with improved survival in ibrutinib-treated patients from the PHOENIX trial cohort with the MCD genetic subtype, which is associated with ABC-DLBCL. Finally, the targeted therapeutic delivery of miR-28 via aptamer-guided nanoparticles suppresses ibrutinib-resistant tumor growth in vivo. These findings identify miR-28 as an effective inhibitor of ibrutinib resistance, underscoring its translational potential as an adjunct strategy in ABC-DLBCL therapy.
    DOI:  https://doi.org/10.1038/s41375-026-02948-9
  28. Haematologica. 2026 Apr 09.
    Relapse as a return, not a reinvention - genomic stability and pre-existing resistance in mantle cell lymphoma.
    Christiane Pott.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2025.289129
  29. Cancer. 2026 Apr 15. 132(8): e70390
    Treatment and outcomes of pulmonary mucosa-associated lymphoid tissue lymphoma: A multicenter analysis of 186 patients.
    Kazutaka Suzuki, Kana Miyazaki, Naoko Asano, Hiroyuki Takahashi, Yusuke Koba, Nobuhiro Hiramoto, Ilseung Choi, Hiroshi Arima, Toshiki Uchida, Nobuhiko Nakamura, Hiro Tatetsu, Hideki Uryu, Shunsuke Ito, Takeharu Kato, Hirokazu Sasaki, Tohru Murayama, Junji Hiraga, Naoki Takahashi, Tetsu Kobayashi, Motoshi Takao, Isao Tawara, Motoko Yamaguchi.
       BACKGROUND: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with pulmonary involvement is a rare, indolent lymphoma with no standard treatment approaches.
    METHODS: To clarify patient characteristics, treatment, and prognosis of pulmonary MALT lymphoma in the modern era, a multi-institutional observational study of patients diagnosed between 2013 and 2022 was conducted. A modified Ann Arbor system was used for the analysis.
    RESULTS: Among 186 eligible patients, 131 (70%) had stage IE/IIE disease, whereas 55 (30%) had stage IV disease. No patient had stage III disease. With a median follow-up of 57 months, the 4-year overall survival (OS) rates for the stage IE, IIE, and IV groups were 96%, 92%, and 90%, respectively. The stage IIE and IV groups had similar progression-free survival (PFS) that was significantly worse than that of the stage IE group (p < .001). In stage IE/IIE patients, no differences were found in OS (p = .89) or PFS (p = .90) among the first-line treatment groups. In stage IV patients, the stomach was the most common synchronous extranodal site of involvement (36%). There were no differences in OS among the first-line treatment groups (p = .64).
    CONCLUSIONS: The OS of patients with MALT lymphoma with pulmonary involvement was favorable regardless of first-line treatment modality, including watchful waiting. The short PFS in the stage IIE and IV groups indicates that these groups are candidates for therapeutic development.
    Keywords:  clinical course; first‐line treatment; prognostic factors; pulmonary mucosa‐associated lymphoid tissue lymphoma; retrospective multi‐institutional study
    DOI:  https://doi.org/10.1002/cncr.70390
  30. Mayo Clin Proc. 2026 Apr 10. pii: S0025-6196(26)17341-8. [Epub ahead of print]
    Treatment of Diffuse Large B-Cell Lymphoma.
    Ayo S Falade, Stephen M Ansell.
      Diffuse large B-cell lymphoma, the most common non-Hodgkin lymphoma subtype, represents 30% to 40% of cases globally. It is an aggressive but potentially curable malignant disease with substantial clinical and molecular heterogeneity. Gene expression profiling defines distinct molecular subtypes with differing prognostic and therapeutic implications. Frontline therapy typically involves anthracycline-based chemoimmunotherapy, most commonly rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Treatment strategies are tailored on the basis of disease stage, molecular subtype, patient fitness, and prognostic risk. Limited stage disease may be managed with abbreviated chemotherapy, with or without involved site radiotherapy, whereas advanced stage disease generally requires 6 cycles of R-CHOP. Substituting polatuzumab vedotin for vincristine has been found to be beneficial for select patients. Elderly patients or those with significant comorbidities may require dose-adjusted regimens or palliative approaches prioritizing quality of life. Relapsed or refractory disease presents therapeutic challenges. For fit patients, chimeric antigen receptor T-cell therapy has emerged as the preferred option in early relapse (<12 months) or refractory disease. Patients with late relapse (>12 months) receive salvage chemotherapy followed by autologous stem cell transplantation. Disease progression after second-line therapy may be treated with bispecific antibodies, antibody-drug conjugates, or novel antibody combinations. Central nervous system involvement portends poor prognosis and requires methotrexate-based therapy. Event-free survival at 24 months has emerged as a strong surrogate marker for long-term outcomes; patients who achieve this have survival comparable to that of the general population. Ongoing advances in molecular characterization, immunotherapy, and precision medicine are expected to further refine risk-adapted, personalized approaches for the treatment of diffuse large B-cell lymphoma.
    DOI:  https://doi.org/10.1016/j.mayocp.2026.01.017
  31. J Cell Mol Med. 2026 Apr;30(7): e71036
    Targeting BCL-xL in Myeloid Malignancies: From Inhibitors to PROTAC.
    Daniela Cilloni, Alessandro Ferrando, Francesco Frassoni.
      Restoring apoptosis in malignant cells represents a central goal of anticancer therapy. Tumour cells often escape cell death by overexpressing anti-apoptotic members of the BCL-2 protein family, particularly BCL-2, BCL-xL, and MCL1. These proteins inhibit the intrinsic mitochondrial apoptotic pathway through intricate interactions with pro-apoptotic partners and direct modulation of the mitochondrial outer membrane. Their pivotal role in cell survival has established them as attractive therapeutic targets. Over the past two decades, significant efforts have been devoted to developing selective small-molecule inhibitors capable of neutralising these proteins and reactivating apoptosis. A first milestone was the discovery of ABT-263 (navitoclax), a dual BCL-2/BCL-xL inhibitor. Building on this achievement, the development of venetoclax, a highly selective BCL-2 inhibitor, marked a major breakthrough, demonstrating potent pro-apoptotic activity and clinical efficacy in several leukaemia subtypes. Despite these advances, the design of inhibitors of BCL-2 family members remains challenging, largely due to the structural characteristics of the BH3-binding groove, which is both shallow and hydrophobic, complicating the identification of molecules with optimal binding affinity and selectivity. PROTACs targeting BCL-xL may represent a promising future strategy, potentially overcoming the intrinsic limitations of small molecule inhibitors.
    Keywords:  BCL‐2; BCL‐2 inhibitors; BCL‐xL; PROTAC
    DOI:  https://doi.org/10.1111/jcmm.71036
  32. Acta Diabetol. 2026 Apr 06.
    Differentiating polycythemia vera from sodium-glucose cotransporter 2 inhibitor-associated polycythemia.
    Ivan Krecak, Marija Valovicic Krecak, Tina Marketin, Marta Marcinkovic, Hrvoje Holik, Marko Skelin, Josipa Budimir, Marko Lucijanic, Sanja Klobucar.
      
    Keywords:  Complete blood count; Erythrocytosis; polycythemia vera; Myeloproliferative neoplasms; Sodium-glucose cotransporter 2 inhibitors
    DOI:  https://doi.org/10.1007/s00592-026-02651-2
  33. Hemasphere. 2026 Mar;10(3): e70335
    Correction to "Outcomes of patients with relapsed or refractory primary mediastinal B-cell lymphoma treated with anti-CD19 CAR-T cells: CARTHYM, a study from the French national DESCAR-T registry".
      [This corrects the article DOI: 10.1002/hem3.70091.].
    DOI:  https://doi.org/10.1002/hem3.70335
  34. Eur J Haematol. 2026 Apr 06.
    Relapse Despite MRD Negativity in Multiple Myeloma: Toward Integrated Risk Prediction.
    Enrica Antonia Martino, Santino Caserta, Mamdouh Skafi, Ernesto Vigna, Antonella Bruzzese, Nicola Amodio, Marco Fiorillo, Eugenio Lucia, Graziella D'Arrigo, Virginia Olivito, Caterina Labanca, Francesco Mendicino, Maria Eugenia Alvaro, Giovanni Tripepi, Fortunato Morabito, Massimo Gentile.
      
    DOI:  https://doi.org/10.1111/ejh.70193
  35. Lancet Haematol. 2026 Apr;pii: S2352-3026(26)00031-1. [Epub ahead of print]13(4): e197-e198
    Concomitant or sequential lower intensity triplet therapy in AML.
    Jayastu Senapati, Naval G Daver, Jayanshu Jain, Alice S Mims.
      
    DOI:  https://doi.org/10.1016/S2352-3026(26)00031-1
  36. Hemasphere. 2026 Mar;10(3): e70347
    Dynamics of BCR::ABL1 transcript levels and clinical outcomes after switch to second-line therapy in pediatric chronic myeloid leukemia.
    Stephanie Sembill, Thomas Zerjatke, Micha Winterstein, Tabita Ghete, Elke Schirmer, Zofia Wotschofsky, Meinolf Suttorp, Manuela Krumbholz, Axel Karow, Ingmar Glauche, Markus Metzler.
      
    DOI:  https://doi.org/10.1002/hem3.70347
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