bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–05–24
thirteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Efficacy and safety of elranatamab in patients with relapsed or refractory multiple myeloma: A US subgroup analysis from MagnetisMM-3.
  2. No need to wait: treat iron deficiency in the hospital.
  3. Venetoclax Plus Pediatric Regimen in Adolescents and Adults with Ph-Negative Acute Lymphoblastic Leukemia.
  4. Long term outcomes of idasanutlin therapy in hydroxyurea-refractory polycythemia vera patients.
  5. Anti-BCMA/GPRC5D CAR T in relapsed or refractory multiple myeloma patients with extraosseous extramedullary disease.
  6. HMA + venetoclax triplet regimens for the initial treatment of AML in adults- CONTRA.
  7. [Analysis of the efficacy of half-dose venetoclax combined with reduced-dose HA regimen in the induction therapy of acute myeloid leukemia].
  8. Zanubrutinib potentiates polatuzumab vedotin efficacy in DLBCL with concurrent CD79b upregulation.
  9. Extended Versus Standard Hypomethylating Agent Dosing in Combination With Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia.
  10. Refractoriness in TTP: challenges and solutions.
  11. [Recent advances in the management of iron deficiency and iron deficiency anemia during pregnancy].
  12. IV iron for IDA during acute infection.
  13. Sustained response after rilzabrutinib discontinuation in multirefractory immune thrombocytopenia.
  1. Cancer. 2026 Jun 01. 132(11): e70442
    Efficacy and safety of elranatamab in patients with relapsed or refractory multiple myeloma: A US subgroup analysis from MagnetisMM-3.
    Ajay K Nooka, Christopher Strouse, Sarah M Larson, Alexander Lesokhin, Asya Varshavsky-Yanovsky, David H Vesole, Guenther Koehne, Elpitha Soussou, Sharon T Sullivan, Jay Cheng, Noopur Raje.
       INTRODUCTION: Elranatamab, approved for relapsed or refractory multiple myeloma, demonstrated deep, durable responses and manageable safety in patients without prior B-cell maturation antigen (BCMA)-directed therapy (BCMA-naive) in MagnetisMM-3 (NCT04649359). This post hoc analysis evaluated efficacy and safety in the US subgroup.
    METHODS: Following step-up dosing, patients received 28-day cycles of elranatamab 76 mg once weekly. After ≥6 cycles, patients with partial response or better persisting for ≥2 months transitioned to every 2 weeks, then to every 4 weeks after ≥6 every-2-week cycles. This analysis included all US-enrolled BCMA-naive patients who received ≥1 elranatamab dose.
    RESULTS: Of the 123 evaluable patients, 47 were enrolled in the United States (38.2%). At a median follow-up of 39.6 months, the objective response rate was 66.0% (95% CI, 50.7-79.1); 42.6% (95% CI, 28.3-57.8) achieved complete response or better. Median (95% CI) duration of response, progression-free survival, and overall survival were 40.8 (24.0-not estimable [NE]), 27.3 (4.3-NE), and 43.6 (14.9-NE) months, respectively. Common (≥60%) treatment-emergent adverse events (any grade; grade 3/4) included infections (70.2%; 42.6%), fatigue (61.7%; 8.5%), and cytokine release syndrome (61.7%; 0%). Twenty-two patients switched from once weekly to every-2-week dosing, then eight switched from every-2-week to every-4-week dosing. Of 18 responders who switched from once weekly to every-2-week dosing and eight responders who further reduced to every 4 weeks, 77.8% and 87.5%, respectively, maintained or improved their response for ≥6 months thereafter.
    CONCLUSION: Elranatamab demonstrated durable responses and manageable safety in the heavily pretreated US subgroup, consistent with the overall MagnetisMM-3 BCMA-naive population.
    Keywords:  MagnetisMM‐3; US subgroup; bispecific antibody; efficacy; elranatamab; multiple myeloma
    DOI:  https://doi.org/10.1002/cncr.70442
  2. Blood. 2026 May 21. 147(21): 2425-2426
    No need to wait: treat iron deficiency in the hospital.
    Jacquelyn M Powers.
      
    DOI:  https://doi.org/10.1182/blood.2026033268
  3. Blood. 2026 May 21. pii: blood.2026033577. [Epub ahead of print]
    Venetoclax Plus Pediatric Regimen in Adolescents and Adults with Ph-Negative Acute Lymphoblastic Leukemia.
    Xiaoyuan Gong, Yuntao Liu, Qiuyun Fang, Runxia Gu, Kaiqi Liu, Dong Lin, Chunlin Zhou, Guangji Zhang, Benfa Gong, Shuning Wei, Yan Li, Shouyun Li, Ying Wang, Shaowei Qiu, Bingcheng Liu, Ying Wang, Yingchang Mi, Hui Wei, Jianxiang Wang.
      The BCL-2 inhibitor venetoclax has shown promise in acute lymphoblastic leukemia (ALL), but its role in first-line therapy for newly diagnosed (ND) Philadelphia chromosome-negative (Ph⁻) ALL is undefined. In this prospective phase 2 study, 167 adolescents and adults (aged 14-60 years) with ND Ph⁻ ALL received venetoclax combined with pediatric-inspired chemotherapy. The primary endpoint was the rate of measurable residual disease (MRD) negativity by multiparameter flow cytometry (MFC) after induction. The complete remission rate was 91.0%, and 73.0% of responders achieved MFC-MRD negativity, meeting the primary endpoint. After a median follow-up of 19.3 months, median overall and disease-free survival were not reached; estimated 2-year survival rates were 78.5% and 76.7%, respectively. Propensity score-matched analysis confirmed superior survival compared with historical chemotherapy-only controls. Grade ≥ 3 adverse events were primarily hematologic toxicities and infections, with an incidence comparable to that of the historical cohort. These results demonstrate that adding venetoclax to pediatric-inspired chemotherapy significantly improves MRD response and survival outcomes in ND Ph⁻ ALL, with a manageable safety profile. This trial was registered with ClinicalTrials.gov under the identifier NCT05660473.
    DOI:  https://doi.org/10.1182/blood.2026033577
  4. Leuk Lymphoma. 2026 May 18. 1-4
    Long term outcomes of idasanutlin therapy in hydroxyurea-refractory polycythemia vera patients.
    Megan Metzger, Julian A Waksal, Jayanshu Jain, Natalia Rosas, Margherita Maffioli, Grace Van Hyfte, Aaron Gerds, Vikas Gupta, Francesco Passamonti, Abdulraheem Yacoub, Ronald Hoffman, John O Mascarenhas.
      Idasanutlin is a small molecule inhibitor that restores p53 activity, triggering apoptosis. Two trials (phase 1/2) of idasanutlin therapy in polycythemia vera patients that were intolerant or refractory to hydroxyurea resulted in substantial clinical and molecular responses. Here the long term outcomes of these patients are reported.
    Keywords:  Myeloproliferative neoplasm; idasanutlin; polycythemia vera
    DOI:  https://doi.org/10.1080/10428194.2026.2666850
  5. Blood. 2026 May 21. pii: blood.2026033506. [Epub ahead of print]
    Anti-BCMA/GPRC5D CAR T in relapsed or refractory multiple myeloma patients with extraosseous extramedullary disease.
    Dian Zhou, Yuekun Qi, Sha Ma, Qian Sun, Weiying Gu, Jieyun Xia, Xiaotian Zhang, Wei Chen, Hai Cheng, Kunming Qi, Feng Zhu, Fan Xia, Lili Zhu, Hujun Li, Huanxin Zhang, Dongmei Yan, Tingting Qiu, Yanlei Zhang, Shuixiu Peng, Wei Sang, Depeng Li, Alex H Chang, Bin Pan, Zhiling Yan.
      Relapsed or refractory multiple myeloma (RRMM) patients with extraosseous extramedullary disease (EMD) have inferior outcomes and lack effective therapies. We developed anti-BCMA/GPRC5D bispecific chimeric antigen receptors (CARs) to investigate the activity and safety of the CAR T cells in patients with extraosseous EMD. In this single-arm, open-label, phase 2 trial, we enrolled 37 RRMM patients with extraosseous EMD, and anti-BCMA/GPRC5D bispecific CAR T cells were administered at 2·0×10⁶ CAR T cells per kilogram. At a median follow-up of 10·1 months (IQR 6·4-19·1), 36 (97%) of 37 patients obtained an overall response and measurable residual disease (MRD) negativity, including 16 (43%) with stringent complete response (sCR). The median progression-free survival (PFS) was 5·8 months (95% confidence interval [CI]: 2·2-9·4), and the median overall survival (OS) was not reached. The most common grade 3 or worse adverse events were hematologic toxicities (except lymphopenia) (37/37). 27 (73%) patients experienced cytokine release syndrome (CRS), of which all cases were grade 1 or 2. Two (5%) patients had grade 1 or 3 immune effector cell-associated neurotoxicity syndrome (ICANS). These findings support that anti-BCMA/GPRC5D bispecific CAR T cells induced a high response rate in RRMM patients with extraosseous EMD, and the safety profile was manageable. This trial was registered with ClinicalTrials.gov (NCT05509530) and is ongoing.
    DOI:  https://doi.org/10.1182/blood.2026033506
  6. Blood Adv. 2026 May 21. pii: bloodadvances.2025018556. [Epub ahead of print]
    HMA + venetoclax triplet regimens for the initial treatment of AML in adults- CONTRA.
    Maximilian Stahl, Richard M Stone.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2025018556
  7. Zhonghua Xue Ye Xue Za Zhi. 2026 Apr 14. 47(4): 379-382
    [Analysis of the efficacy of half-dose venetoclax combined with reduced-dose HA regimen in the induction therapy of acute myeloid leukemia].
    Z S Yan, X H Suo, G C Bai, B Zhang, J S He, J S Li, S N Wei, Q L Li, K Q Liu, Y C Mi.
      We retrospectively analyzed clinical data on newly diagnosed acute myeloid leukemia (AML) patients who received HAV treatment between June 2020 and April 2023. The HAV regimen includes venetoclax at 100 mg on day 0 and 200 mg from day 1 to 14, administered orally; homoharringtonine at 2 mg/m(2) from day 3 to 9, given by intravenous infusion; and cytarabine at 50 mg/m(2) from day 3 to 9, also administered by intravenous infusion. Among 33 patients, 36.4% (12/33) were male, with a median age of 60 years (range, 14-67 years). The overall response rate after one cycle of induction therapy was 90.9%, and the complete response (CR) rate was 87.9%. Among the patients, 79.3% achieved CR with measurable residual disease negativity. No patient died during induction therapy. The median recovery times of neutrophils (≥1.0×10(9)/L) and platelets (≥30×10(9)/L) were 10 (5-12) days and 10 (3-13) days, respectively. Until October 30, 2024, the estimated 3-year overall survival rate, event-free survival rate, and disease-free survival rate were 68.2% (95% CI: 59.7% -76.7% ), 66.7% (95% CI: 58.5% -74.9% ), and 73.6% (95% CI: 65.6% -81.6% ), respectively. HAV is a highly effective and safe induction therapy regimen for patients with newly diagnosed AML.
    DOI:  https://doi.org/10.3760/cma.j.cn121090-20250516-00232
  8. Ann Hematol. 2026 May 19.
    Zanubrutinib potentiates polatuzumab vedotin efficacy in DLBCL with concurrent CD79b upregulation.
    Xiaolong Zhou, Jingjing Li, Zipeng Zhao, Jie Liu, Junyi Zhang, Wen Zhou, Ailing Gui, Yichen Yan, Shun Zhu, Wen Liu, Ji Zuo, Qunling Zhang, Ling Yang.
      In diffuse large B-cell lymphoma (DLBCL), although most patients are curable, the approximately one-third who experience refractory or relapsed disease face a poor prognosis, underscoring the need for novel therapeutic strategies. Although Bruton's tyrosine kinase inhibitors (BTKis) exhibit anti-lymphoma activity in various B-cell malignancies, they are less effective in patients with the germinal center B-cell-like (GCB) subtype. The anti-CD79b antibody-drug conjugate polatuzumab vedotin has been approved for DLBCL treatment. Previous studies have shown that the combination of the second-generation BTKi zanubrutinib and polatuzumab vedotin, within the R-CHOP regimen, yielded higher response rates in preliminary clinical studies; however, the efficacy of this combination remains unclear. This study aimed to evaluate whether zanubrutinib plus polatuzumab vedotin could represent a novel therapeutic approach. Through assays of drug combination, cell proliferation, cell cycle, and apoptosis, we demonstrated that this combination synergistically inhibited DLBCL cell proliferation both in vitro and in vivo. Moreover, zanubrutinib enhanced polatuzumab vedotin-induced G2/M phase arrest and apoptosis in DLBCL cells, accompanied by increased CD79b expression. Notably, the combination showed superior synergistic efficacy in GCB-subtype cells. In conclusion, these findings provide a novel mechanistic rationale for combining zanubrutinib and polatuzumab vedotin in DLBCL treatment, regardless of cell-of-origin subtype.
    Keywords:  DLBCL; Polatuzumab vedotin; Zanubrutinib
    DOI:  https://doi.org/10.1007/s00277-026-07067-0
  9. Hematol Oncol. 2026 May;44(3): e70198
    Extended Versus Standard Hypomethylating Agent Dosing in Combination With Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia.
    Georgio Medawar, Jean-Sebastien Anoma, Elizabeth Hill, Serena Tharakan, Dahniel L Sastow, Vincent Lok, Su Bin Hahn, Sarah Chen, Thomas Kehoe, Chidambaram Ramasamy, Julian Guetta-Weiss, Kapil Meleveedu, Chenyu Lin, David M Swoboda, Douglas Tremblay, Alexander Coltoff.
      The optimal duration of hypomethylating agent (HMA) therapy combined with venetoclax (Ven) in newly diagnosed acute myeloid leukemia (ND-AML) remains uncertain. Standard of care (SOC) uses 5-day decitabine (Dec-5) or 7-day azacitidine (Aza-7), while extended HMA regimens (e.g., 10-day decitabine [Dec-10] during cycle 1) have also been explored, although direct comparative data between these approaches are limited. We conducted a large retrospective analysis of 335 patients with ND-AML treated at five US centers with Dec-10/Ven (n = 102) or SOC HMA/Ven (n = 233). Baseline characteristics were largely balanced, though the Dec-10 group had more treated secondary AML, and the SOC group had more intermediate risk by ELN-2024. Dec-10/Ven exhibited significantly higher composite complete remission rates (CRc) (82% vs. 70%, p = 0.029), but similar measurable residual disease (MRD) negativity rates (27% vs. 25%, p = 0.6) at best response. Median overall survival (OS) was significantly longer for Dec-10/Ven, 22.2 versus 9.1 months for SOC (p < 0.001). Transplantation was more frequent following Dec-10/Ven (25% vs. 6%, p < 0.001). The 30-day and 60-day mortality rates were similar (7% vs. 11%, p = 0.4; 13% vs. 23%, p = 0.1). On multivariable analysis, the Dec-10 regimen, de novo AML, non-complex karyotype, and IDH2 mutation were associated with a significantly lower risk of death. Our findings suggest that Dec-10/Ven may lead to improved transplant rates and survival, providing valuable real-world support for this intensified approach in appropriate patients. Prospective randomized evaluation is warranted.
    Keywords:  acute myeloid leukemia; azacitidine; decitabine; duration; outcomes
    DOI:  https://doi.org/10.1002/hon.70198
  10. Blood. 2026 May 21. 147(21): 2418-2420
    Refractoriness in TTP: challenges and solutions.
    Marie Scully.
      
    DOI:  https://doi.org/10.1182/blood.2026033269
  11. Zhonghua Xue Ye Xue Za Zhi. 2026 Apr 14. 47(4): 399-403
    [Recent advances in the management of iron deficiency and iron deficiency anemia during pregnancy].
    J Zhang, M Chen.
      Iron deficiency (ID) and iron deficiency anemia (IDA) are common obstetric complications associated with various adverse pregnancy outcomes. According to the latest evidence-based medical evidence, this article reviews the management strategies for ID and IDA during pregnancy. Intravenous iron therapy provides substantial advantages for patients who cannot tolerate or do not respond to oral iron, as well as for those with severe IDA requiring rapid correction. The application of new-generation intravenous iron agents has improved treatment efficiency; however, their safety in the first trimester warrants further evaluation. Further, monitoring for adverse events, including hypophosphatemia, is necessary. This review further examines the differential diagnosis and management of intravenous iron-related hypersensitivity reactions and complement activation-related pseudoallergy. Management should be individualized based on patient-specific factors in clinical practice, with adherence to evidence-based guidelines to optimize maternal and infant outcomes.
    DOI:  https://doi.org/10.3760/cma.j.cn121090-20250826-00402
  12. Blood. 2026 May 21. 147(21): 2556
    IV iron for IDA during acute infection.
      
    DOI:  https://doi.org/10.1182/blood.2026034127
  13. Blood Vessel Thromb Hemost. 2026 May;3(2): 100167
    Sustained response after rilzabrutinib discontinuation in multirefractory immune thrombocytopenia.
    Tomás José González-López, Fernando Orza, Amalia Cuesta-García, Noelia Pérez-Gómez, José Luis Fedele, Drew Provan, David J Kuter.
      
    DOI:  https://doi.org/10.1016/j.bvth.2026.100167
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