bims-hemali Biomed News
on Hematologic malignancies
Issue of 2025–03–30
eleven papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. VRd vs. VPd as induction therapy in high risk newly diagnosed multiple myeloma.
  2. Daratumumab-Bortezomib-Thalidomide-Dexamethasone for Newly Diagnosed Myeloma: CASSIOPEIA Minimal Residual Disease Results.
  3. How I treat chronic myeloid leukemia in children and adolescents.
  4. Atypical chronic myeloid leukemia: from cytology to molecular characterization.
  5. SUMOylation facilitates the stability of BCR-ABL to promote chronic myeloid leukemia progression.
  6. Loncastuximab Tesirine Versus Polatuzumab Vedotin Plus Bendamustine and Rituximab in Relapsed/Refractory DLBCL After ≥ 2 Lines of Therapy: Matching-Adjusted Indirect Comparison.
  7. Outcomes of Newly Diagnosed Multiple Myeloma Patients Requiring Dialysis.
  8. 5-FU@HFn combined with decitabine induces pyroptosis and enhances antitumor immunotherapy for chronic myeloid leukemia.
  9. Extramedullary Multiple Myeloma: Challenges and Opportunities.
  10. PGE2 inhibition to prevent AML escape from NK cells.
  11. Cytogenetic abnormalities in polycythemia vera: phenotypic correlates and prognostic relevance in 669 informative cases.
  1. Sci Rep. 2025 Mar 22. 15(1): 9946
    VRd vs. VPd as induction therapy in high risk newly diagnosed multiple myeloma.
    Chun Yan Li, Long Zhong, Dan Gui Chen, Fu Sheng Yao, Hong Yan.
      In high-risk newly diagnosed multiple myeloma (HRNDMM), two different induction regimens were evaluated for safety and efficacy: Bortezomib-Pomalidomide-Dexamethasone (VPd) and Bortezomib-Lenalidomide-Dexamethasone (VRd). Newly diagnosed high-risk MM patients(age > 18) were included in this retrospective study, who received VRd and VPd induction therapy between January 2021 and November 2023. All methods of this experiment were performed in accordance with relevant guidelines and regulations. Informed consent has been obtained from all subjects and/or their legal guardians. The Ethics Association of Anqing City Hospital has approved the study on pomadomide in this experiment (Medical Review (2021) No. 27). The evaluation of OS (overall survival), PFS (progression free survival), AE (adverse event) was the secondary endpoints, while the primary endpoint of the study was the overall response rate (ORR) after four cycles of VRd and VPd. Ultimately, 25 patients with VRd and 21 patients with VPd were enrolled. After four cycles of induction, stringent complete, complete, very good partial, partial and overall response rates were 16%/24%/12%/40%/92% with VRd, and 23.81%/33.33%/33.33%/9.52%/100% with VPd. VGPR or better was achieved in 52% of patients receiving VRd compared to 90.47% in those receiving VPd, with a p-value of 0.003. VPd was linked to more cases of skin rash (p = 0.02). For VRd and VPd, the average overall survival time was 27-months and 21-months, respectively (p = 0.801). The PFS was 27-months for VRd and 20-months for VPd (p = 0.116). Median OS and PFS were not defined in both groups. According to our research, the induction of VPd has been found to elicit more profound and superior responses in HRNDMM compared to VRd, thereby establishing its safety. Our results underscore the potential clinical advantage of pomalidomide as first-line therapy and offer more proof of the beneficial efficacy of VPd in the treating of HRNDMM patients.
    Keywords:  High risk; Lenalidomide; Newly diagnosed multiple myeloma; Pomalidomide; Triple therapy
    DOI:  https://doi.org/10.1038/s41598-025-85398-0
  2. Blood. 2025 Mar 24. pii: blood.2024027620. [Epub ahead of print]
    Daratumumab-Bortezomib-Thalidomide-Dexamethasone for Newly Diagnosed Myeloma: CASSIOPEIA Minimal Residual Disease Results.
    Jill Corre, Laure Vincent, Philippe Moreau, Benjamin Hebraud, Cyrille Hulin, Marie-Christine Béné, Annemiek Broijl, Denis Caillot, Michel Delforge, Thomas Dejoie, Thierry Facon, Jerome Lambert, Xavier Leleu, Margaret Macro, Aurore Perrot, Sonja Zweegman, Thomas Filleron, Bastien Cabarrou, Niels W C J van de Donk, Sabrina Mahéo, Winnie Hua, Jianping Wang, Maria Krevvata, Véronique Vanquickelberghe, Carla de Boer, Alba Tuozzo, Fredrik Borgsten, Melissa Rowe, Robin Carson, Soraya Wuilleme, Pieter Sonneveld.
      Previous results from CASSIOPEIA (NCT02541383) demonstrated superior progression-free survival (PFS) and minimal residual disease (MRD) negativity with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (VTd) induction/consolidation and with daratumumab maintenance versus observation in transplant-eligible newly diagnosed multiple myeloma (NDMM). Here, we present long-term MRD status and PFS outcomes after an 80.1-month median follow-up. Patients were randomly assigned (1:1) to daratumumab plus VTd (D-VTd) or VTd induction/consolidation; patients remaining on study were re-randomized to daratumumab maintenance or observation for £2 years. MRD status was assessed at pre-defined timepoints during each study phase. D-VTd improved overall MRD-negativity rates (10-5) post-induction (34.6% vs 23.1%; P<0.0001) and post-consolidation (63.7% vs 43.7%; P<0.0001) and provided PFS benefit, regardless of post-induction MRD status, versus VTd alone. Daratumumab maintenance improved overall MRD-negativity rates over observation, regardless of induction/consolidation treatment (D-VTd/daratumumab vs D-VTd/observation: 10-5, 77.3% vs 70.7% [P=0.0417]; 10-6, 60.7% vs 52.0% [P=0.0365]; VTd/daratumumab vs VTd/observation: 10-5, 70.9% vs 51.2% [P<0.0001]; 10-6, 48.4% vs 30.7% [P<0.0001]), and improved MRD-negativity rates, regardless of risk status, as defined by cytogenetic abnormalities or revised International Staging System score. Further, daratumumab maintenance provided PFS benefit versus observation, regardless of induction/consolidation treatment and post-consolidation MRD status. D-VTd followed by daratumumab maintenance consistently produced the highest landmark, accumulative, and sustained MRD-negativity rates (10-5 and 10-6), translating to superior long-term PFS outcomes. These results demonstrate that daratumumab-based induction/consolidation followed by daratumumab maintenance resulted in the deepest and most durable MRD negativity, leading to superior PFS outcomes.
    DOI:  https://doi.org/10.1182/blood.2024027620
  3. Blood. 2025 Mar 25. pii: blood.2024026514. [Epub ahead of print]
    How I treat chronic myeloid leukemia in children and adolescents.
    Jing Chen, Meinolf Suttorp, Nobuko Hijiya.
      Chronic myeloid leukemia (CML) is rare in children and adolescents. Although outcomes have dramatically improved owing to tyrosine kinase inhibitors (TKIs) in the last two decades, there are still many challenges related to the management of pediatric CML, including the impact of TKIs on growth deceleration and unknown long-term adverse effects as well as defining the role of treatment-free remission. Unlike adult CML, which is driven by evidence-based guidelines, management of pediatric CML is often extrapolated from adult guidelines. However, pediatric CML differs from adult CML in many ways, presenting with different biological, molecular, and most importantly, host factors that make it necessary for a different treatment approach. Following the initial approval of first-generation imatinib for pediatric CML in 2003, three TKIs, all second-generation TKIs (2G-TKIs), have been approved, including dasatinib, nilotinib and bosutinib, which has greatly expanded therapeutic options but also added complexity to treatment determination. The expanded treatment options also call into question the treatment choice for pediatric CML, long-term efficacy and safety profiles of these TKIs. We present three cases commonly encountered in pediatric CML, their challenges and relevant issues as well as recommended managements.
    DOI:  https://doi.org/10.1182/blood.2024026514
  4. Blood. 2025 Mar 27. 145(13): 1438
    Atypical chronic myeloid leukemia: from cytology to molecular characterization.
    Aida Calo-Pérez, Raquel Martínez-Fernández.
      
    DOI:  https://doi.org/10.1182/blood.2024027505
  5. Oncogene. 2025 Mar 27.
    SUMOylation facilitates the stability of BCR-ABL to promote chronic myeloid leukemia progression.
    Lu Zhang, Xuefeng Wang, Dongmei Hu, Shijie Li, Mingshan Sun, Qian Liu, Huimin Feng, Minran Zhou, Chunyan Chen, Huan Zhou, Sai Ma.
      Tyrosine kinase inhibitors (TKIs) targeting the oncoprotein BCR-ABL have improved the prognosis for patients with chronic myeloid leukemia (CML). However, TKI resistance and persistent expression of BCR-ABL are responsible for the relapse and progression of CML. Here, we describe a novel approach to induce BCR-ABL protein degradation by small ubiquitin-like modifier (SUMO) modification. The E3 SUMO ligase TRIM28, upregulated during the progression of CML, promoted SUMOylation of BCR-ABL, thereby inhibiting its binding to the autophagy receptor P62 and repressing its autophagic degradation. Accordingly, genetic and pharmacological inhibition of TRIM28 or SUMOylation suppressed progression in both the CML mouse model and patient-derived xenograft model. Furthermore, targeting SUMOylation of BCR-ABL restrained the proliferation of TKI-resistant CML cells. These results identify the mechanism by which TRIM28 maintains BCR-ABL stability to promote CML progression and suggest SUMOylation as a target for CML treatment.
    DOI:  https://doi.org/10.1038/s41388-025-03350-y
  6. Adv Ther. 2025 Mar 28.
    Loncastuximab Tesirine Versus Polatuzumab Vedotin Plus Bendamustine and Rituximab in Relapsed/Refractory DLBCL After ≥ 2 Lines of Therapy: Matching-Adjusted Indirect Comparison.
    Koo Wilson, Francesca Chiodi, Abby Paine, Zalmai Hakimi, Victoria Ward, Tom Macmillan, Daniel Eriksson, Silvia Mappa.
       INTRODUCTION: Despite recent approvals of new treatments, relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains challenging to treat, with limited durable responses and a high proportion of patients relapsing after two or more lines of therapy. Loncastuximab tesirine (Lonca) is a highly potent CD19-targeted antibody drug conjugate with convenient dosing for patients with third-line R/R DLBCL.
    METHODS: In the absence of head-to-head trials, unanchored matching-adjusted indirect comparisons (MAICs) were conducted to compare the relative efficacy and safety of Lonca with polatuzumab vedotin + bendamustine and rituximab (Pola + BR).
    RESULTS: Four studies included in the MAICs were identified via systematic review and hand-searching. Lonca (LOTIS-2) was compared with three comparator studies for Pola + BR (GO29365 extension study, COTA database, Dal et al. 2023). Overall, there was no evidence of a difference in overall response and complete response (CR) rates. Despite Pola + BR demonstrating a higher CR rate in the GO29365 extension study, this did not translate into significant improvements in progression-free or overall survival. Survival analyses indicated similar efficacy between treatments across studies, with most comparisons/meta-analyses showing no statistically significant differences. Lonca had significantly lower odds of Grade 3-4 infections, any serious adverse event (SAE), and specific SAEs including febrile neutropenia, pneumonia and pyrexia. Of the safety endpoints analyzed, none indicated significant differences in favor of Pola + BR.
    CONCLUSION: These results suggest no evidence of a difference in efficacy between the two treatments and potentially more favorable safety profile for Lonca compared with Pola + BR in patients with R/R DLBCL after two or more lines of treatment.
    Keywords:  Antibody–drug conjugates; Comparative efficacy; Diffuse large B-cell lymphoma; Loncastuximab tesirine; Matching-adjusted indirect comparison; Polatuzumab vedotin plus bendamustine and rituximab; Relapsed/refractory; Response rate
    DOI:  https://doi.org/10.1007/s12325-025-03169-9
  7. Clin Lymphoma Myeloma Leuk. 2025 Mar 04. pii: S2152-2650(25)00079-5. [Epub ahead of print]
    Outcomes of Newly Diagnosed Multiple Myeloma Patients Requiring Dialysis.
    Despina Fotiou, Foteini Theodorakakou, Eirini Solia, Vasiliki Spiliopoulou, Ioannis Ntanasis-Stathopoulos, Panagiotis Malandrakis, Erasmia Psimenou, Nikolaos Kanellias, Maria Roussou, Magdalini Migkou, Evangelos Eleutherakis-Papaiakovou, Angeliki Andrikopoulou, Stavroula Giannouli, Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos.
       INTRODUCTION: Renal impairment (RI) is a common complication in newly diagnosed multiple myeloma (NDMM), with 1-5% of patients presenting with severe RI requiring dialysis, which is associated with significant morbidity and early mortality. Limited real-world data exist on outcomes for these patients.
    AIM/METHODS: We assessed renal response patterns and outcome determinants in 73 consecutive NDMM patients requiring dialysis, treated in a single centre (2010 to 2023).
    RESULTS: Median age was 69 years; 52% had high-risk cytogenetics. All patients received bortezomib-based induction therapy (19% doublets, 71% triplets, 10% quadruplets; 12% anti-CD38 antibodies). Median follow-up was 37.2 months. Dialysis independence was achieved by 31 patients (42.5%) after a median of 52 days (range 3-247). Dialysis independence was associated with improved survival (median 36 vs. 13.3 months, P = .085) and lower early mortality (3.2% vs. 14.3%, P = .15). Factors associated with independence from dialysis were younger age) OR 0.92, P = .003), hypercalcemia (OR 1.43, P = .013) and hematologic response (≥ PR) at 1 month (OR 3.7, P = .015). In multivariate analysis, younger age (P = .012, OR 0.93) and hematologic response (≥ PR) at 1 month (P = .014, OR 4.94) were independent predictors of dialysis independence. Depth of hematologic response (≥ VGPR) significantly impacted renal recovery (OR 4.0, P = .020). High-risk cytogenetics independently predicted poor outcomes (HR 3.67, P = .003).
    CONCLUSION: Dialysis independence is achievable in 42.5% of NDMM patients without special filters in the era of bortezomib-based regimens, with significant impact on outcome. Outcomes remain poor overall for patients who are dialysis-dependent at diagnosis and further evaluation of quadruplet regimens with anti-CD38 antibodies is needed.
    Keywords:  Bortezomib-based treatment; Dialysis-dependence; Novel agents; Overall survival; Renal response
    DOI:  https://doi.org/10.1016/j.clml.2025.03.003
  8. J Nanobiotechnology. 2025 Mar 28. 23(1): 252
    5-FU@HFn combined with decitabine induces pyroptosis and enhances antitumor immunotherapy for chronic myeloid leukemia.
    Zuowei Yuan, Guoyun Jiang, Ying Yuan, Qian Liang, Yaxin Hou, Wenyao Zhang, Lujia Tang, Kelong Fan, Wenli Feng.
       BACKGROUND: Tyrosine kinase inhibitors (TKIs) constitute the primary treatment for chronic myeloid leukemia (CML). However, resistance to TKIs often leads to treatment failure. Pyroptosis, a form of programmed cell death, has emerged as a promising strategy in cancer therapy due to its ability to eliminate tumor cells while stimulating antitumor immunity. Low-dose decitabine (DAC) has been shown to reverse methylation-induced silencing of the pyroptosis-related gene gasdermin E (GSDME) in some tumor cells, offering a potential new therapeutic option for CML. Herein, we propose a combination therapy using 5-fluorouracil (5-FU), a broad-spectrum chemotherapeutic agent, and low-dose DAC to induce pyroptosis in CML cells via the caspase-3/GSDME pathway. However, the nonspecific targeting of 5-FU diminishes its pyroptosis efficacy and causes off-target toxicity, highlighting the need for a targeted drug delivery system.
    RESULTS: In this study, we developed 5-FU@HFn nanoparticles (NPs) by loading 5-FU into the recombinant human heavy chain ferritin (HFn) nanocage through a high-temperature via the drug channels on the protein cage. The loading efficiency was approximately 50.62 ± 1.17 µg of 5-FU per mg of HFn. 5-FU@HFn NPs selectively targeted CML cells through CD71-mediated uptake, significantly enhancing the therapeutic effects of 5-FU. When combined with DAC, 5-FU@HFn NPs effectively activated pyroptosis via the caspase-3/GSDME pathway in both TKI-sensitive and TKI-resistant CML cells. In a CML mouse model, this combination therapy significantly suppressed tumorigenesis and triggered a robust antitumor immune response, facilitating the clearance of leukemic cells. Furthermore, the 5-FU@HFn NPs exhibited excellent in vivo safety.
    CONCLUSIONS: The innovative therapeutic strategy, combining 5-FU@HFn nanoparticles with low-dose DAC, effectively induces caspase-3/GSDME-mediated pyroptosis and activates antitumor immunity for CML. This approach offers a potential alternative for patients resistant or intolerant to TKIs.
    Keywords:  5-fluorouracil; Antitumor immunity; Chronic myeloid leukemia; Ferritin nanocage; Pyroptosis
    DOI:  https://doi.org/10.1186/s12951-025-03335-9
  9. Curr Oncol. 2025 Mar 20. pii: 182. [Epub ahead of print]32(3):
    Extramedullary Multiple Myeloma: Challenges and Opportunities.
    Matthew Ho, Luca Paruzzo, Janna Minehart, Neel Nabar, Julia Han Noll, Thomas Luo, Alfred Garfall, Saurabh Zanwar.
      Extramedullary multiple myeloma (EMM), defined in this review as soft tissue plasmacytomas resulting from hematogenous spread, is characterized by the ability of MM cells to proliferate outside of the bone marrow microenvironment. It is aggressive, often associated with high-risk cytogenetics and early relapse, and independently portends significantly shorter progression-free and overall survival, even in the era of highly effective immunotherapies. The molecular and microenvironmental factors underlying extramedullary MM dissemination continue to be studied to inform the development of better treatments. In this review, we discuss our current understanding of the biology of EMM, focusing on its distinct molecular and microenvironmental characteristics vis-à-vis MM. We also review the current treatment strategies, acknowledging the paucity of large, randomized studies specific to this population.
    Keywords:  CAR-T; MAPK; bispecific antibodies; paraskeletal disease; relapsed myeloma
    DOI:  https://doi.org/10.3390/curroncol32030182
  10. Blood. 2025 Mar 27. 145(13): 1338-1339
    PGE2 inhibition to prevent AML escape from NK cells.
    Federico Simonetta.
      
    DOI:  https://doi.org/10.1182/blood.2024027931
  11. Haematologica. 2025 Mar 27.
    Cytogenetic abnormalities in polycythemia vera: phenotypic correlates and prognostic relevance in 669 informative cases.
    Moazah Iftikhar, Masooma Rana, Yamna Jadoon, Maymona Abdelmagid, Kaaren Reichard, Cinthya Zepeda Mendoza, Animesh Pardanani, Ayalew Tefferi, Naseema Gangat.
      The main objective of the current study was to provide a detailed account on the prognostic relevance of abnormal karyotype (AK) and associated specific cytogenetic abnormalities in polycythemia vera (PV). 669 PV patients were informative, of which 436 (65%) were evaluated within 1 year of diagnosis. Karyotype was abnormal in 67 (15%) patients, including isolated abnormalities of loss of Y chromosome (-Y; N=15; 3%), +9 (N=11; 3%), del(20q) (N=10; 2%), +8 (N=4; 1%). AK correlated with older age (p.
    DOI:  https://doi.org/10.3324/haematol.2025.287569
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