bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–03–08
27 papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. [The challenge of achieving treatment-free remission for chronic myeloid leukemia].
  2. [How I manage chronic myeloid leukemia patients' fertility].
  3. [Key points in second-line therapy for chronic myeloid leukemia].
  4. [Key points in selecting first-line therapy for chronic myeloid leukemia].
  5. Pretransplant promise for PD-1 in Hodgkin lymphoma.
  6. BCR::ABL1 Mutational Profiling in US Patients With Chronic-phase Chronic Myeloid Leukemia on Tyrosine Kinase Inhibitors.
  7. Five-year interim analysis of J-SKI: an observational study of TKI discontinuation in patients with CML in Japan.
  8. Epcoritamab plus rituximab, dexamethasone, cytarabine, oxaliplatin/carboplatin induces deep and durable responses in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma: results from the EPCORE NHL-2 trial.
  9. Real-world comparison of BTK inhibitors and lenalidomide as first-line maintenance in primary CNS lymphoma: a multi-center retrospective study.
  10. Targeting BCMA: a double-edged sword for infection risk.
  11. Sintilimab, pegaspargase, and anlotinib as induction therapy for advanced-stage NKTCL: a multicenter phase II study.
  12. Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement and Pemigatinib.
  13. Genomic profiling for decision-making in post-polycythemia vera and post-essential thrombocythemia myelofibrosis.
  14. Could a TCR be faster than a CAR?
  15. Selinexor plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: a multicenter, open-label, phase 1 study.
  16. Proteostasis meets signaling: UBE2G1 in hematopoietic stem cell aging.
  17. Fixed-duration VenO vs FCR/BR in fit patients with untreated CLL: primary analysis of the phase 3 CRISTALLO trial.
  18. Odronextamab in people with relapsed or refractory follicular lymphoma: plain language summary of the ELM-2 study.
  19. Ready, set, GO? Treating older adults with AML.
  20. Acute diplopia caused by extramedullary multiple myeloma.
  21. Reduced dose versus standard melphalan conditioning for autologous stem cell transplantation in multiple myeloma: a single-center retrospective study.
  22. TCR T cells targeting IgA- and IgG-expressing multiple myeloma.
  23. Introduction to a review series on hemophagocytic lymphohistiocytosis.
  24. Thrombotic thrombocytopenic purpura: celebrating 25 years of ADAMTS13.
  25. The Changing Landscape of Second Primary Malignancies in Multiple Myeloma: A SEER Population-Based Study Between Two Therapeutic Eras.
  26. REALiTEC: a multi-country observational retrospective study of teclistamab in patients with relapsed/refractory multiple myeloma outside of clinical trials.
  27. Low Serum Cholesterol Is a Biomarker of Advanced Disease and Poor Outcomes in Myeloproliferative Neoplasms.
  1. Rinsho Ketsueki. 2026 ;67(2): 158-164
    [The challenge of achieving treatment-free remission for chronic myeloid leukemia].
    Naoto Takahashi.
      While tyrosine kinase inhibitors (TKIs) have dramatically improved the prognosis for patients with chronic myeloid leukemia (CML), lifelong therapy presents challenges such as long-term toxicities and financial burden. Consequently, treatment-free remission (TFR) has become a primary therapeutic goal, with the aim of safely discontinuing TKIs while maintaining remission and enhancing patient quality of life (QoL). The feasibility and safety of TFR have been established through numerous clinical trials worldwide. The large-scale J-SKI observational study confirmed a 5-year TFR rate of 65.2% and demonstrated its safety in clinical practice. A sustained period of deep molecular response (DMR) is the most critical predictive factor for a successful TFR attempt. Current challenges include TKI withdrawal syndrome, the success of second TFR attempts, and the rare risk of blast crisis during TFR. Future strategies aim to increase TFR eligibility by achieving higher DMR rates with newer agents.
    Keywords:  Deep molecular response; Second TFR attempt; Treatment-free remission; Tyrosine kinase inhibitor
    DOI:  https://doi.org/10.11406/rinketsu.67.158
  2. Rinsho Ketsueki. 2026 ;67(2): 152-157
    [How I manage chronic myeloid leukemia patients' fertility].
    Tomoiku Takaku.
      Tyrosine kinase inhibitors (TKIs) have dramatically improved the prognosis of chronic myeloid leukemia (CML), bringing the CML patients' fertility to the forefront of survivorship care. This review outlines current evidence and pragmatic guidance for patients with CML who desire pregnancy. Ideally, patients should achieve and sustain a deep molecular response (MR4.5), fulfill eligibility criteria for treatment-free remission (TFR), discontinue TKIs, and pursue planned conception under close molecular monitoring. When pregnancy occurs during therapy, TKI exposure should be avoided in the first trimester; interferon-alpha (IFN-α) is the preferred option for disease control. In the event of molecular relapse, carefully considered use of imatinib or nilotinib at the lowest effective dose may be employed exclusively in the second or third trimester following multidisciplinary counseling, whereas dasatinib should be avoided throughout gestation. Available data suggest there is minimal impact of TKIs on male fertility; treatment interruption is generally unnecessary. We emphasize structured algorithms, explicit intervention thresholds, and monthly BCR-ABL1 (IS) testing, as well as collaboration with obstetrics, neonatology, and reproductive medicine, including assisted reproductive technologies. Finally, we discuss practical pathways applicable to resource-limited settings to balance maternal-fetal safety with patient values and to support informed, preference-concordant decision-making.
    Keywords:  Assisted reproductive technology; Chronic myeloid leukemia; Fertility preservation; Tyrosine kinase inhibitor
    DOI:  https://doi.org/10.11406/rinketsu.67.152
  3. Rinsho Ketsueki. 2026 ;67(2): 142-151
    [Key points in second-line therapy for chronic myeloid leukemia].
    Takaaki Ono.
      Tyrosine kinase inhibitors (TKIs) have markedly improved the prognosis of chronic myeloid leukemia (CML). In Japan, in addition to the four established first-line TKIs, asciminib is now approved as an initial therapy, expanding the treatment options. Nevertheless, more than 10% of patients treated with asciminib over 48 weeks, and approximately 20-30% of those receiving other TKIs over five years, require second-line therapy because of resistance or intolerance. As first-line choices diversify, selecting the optimal second-line regimen has become increasingly complex. For intolerance, switching should be guided by the adverse-event profile with attention to potential cross-intolerance. For resistance, assessment of BCR::ABL1 mutations is essential, and second-line agents should be chosen according to the initial TKI and mutation sensitivity. This article summarizes the criteria and timing for switching to second-line therapy and key considerations for selecting and managing second-line TKIs, and briefly reviews the evidence for asciminib and ponatinib in second-line and later settings.
    Keywords:  Asciminib; Chronic myeloid leukemia; Ponatinib; Second-line treatment
    DOI:  https://doi.org/10.11406/rinketsu.67.142
  4. Rinsho Ketsueki. 2026 ;67(2): 130-141
    [Key points in selecting first-line therapy for chronic myeloid leukemia].
    Shinya Kimura.
      Chronic myeloid leukemia (CML) is driven by the BCR::ABL1 fusion gene, and the introduction of tyrosine kinase inhibitors (TKIs) has dramatically improved long-term survival. In Japan, five agents-imatinib (Glivec®), dasatinib (Sprycel®), nilotinib (Tasigna®), bosutinib (Bosulif®), and STAMP inhibitor asciminib (Scemblix®)-are currently approved for first-line therapy. Each has distinct efficacy and toxicity profiles, requiring individualized treatment decisions based on age, comorbidities, cardiovascular risk, fertility, adherence, and financial factors. Recent advances have shifted treatment goals from disease control to treatment-free remission (TFR), with imatinib, dasatinib, and nilotinib supported by robust clinical trial data. Emerging strategies, such as low-dose regimens and step-up dosing of TKI, highlight the importance of balancing efficacy with tolerability and quality of life. Looking forward, immunologic determinants of TFR and novel therapeutic approaches, including targeting CML stem cells with agents such as asciminib or demethylating drugs, may offer prospects for cure. This review summarizes the current evidence and practical considerations in selecting first-line therapy for chronic-phase CML, with a focus on optimizing long-term outcomes and advancing toward individualized and potentially curative strategies.
    Keywords:  Chronic myeloid leukemia; First line; STAMP inhibitor; Tyrosine kinase inhibitor
    DOI:  https://doi.org/10.11406/rinketsu.67.130
  5. Blood. 2026 Mar 05. 147(10): 1015-1017
    Pretransplant promise for PD-1 in Hodgkin lymphoma.
    Ghassan Zammar, Chan Y Cheah.
      
    DOI:  https://doi.org/10.1182/blood.2025032407
  6. Cancer Diagn Progn. 2026 Mar-Apr;6(2):6(2): 186-198
    BCR::ABL1 Mutational Profiling in US Patients With Chronic-phase Chronic Myeloid Leukemia on Tyrosine Kinase Inhibitors.
    Fadi G Haddad, Elias J Jabbour, Stephen W Gutkin, Ashutosh K Pathak, Yifan Zhai, Hagop M Kantarjian.
       Background/Aim: Widespread use of BCR::ABL1 tyrosine kinase inhibitors (TKIs) has transformed the clinical landscape of chronic myeloid leukemia (CML). However, BCR::ABL1 mutation-driven treatment resistance challenges optimal care and outcomes. The purpose of this study was to ascertain real-world practices concerning such mutational profiling in US hematology and oncology practices, which were mainly community-based.
    Materials and Methods: This is the first chart review of BCR::ABL1 kinase domain mutational profiling in the US. In this study of the Cardinal Health Oncology Provider Extended Network (OPEN), 13 hematologists and/or oncologists selected charts of adults with chronic-phase CML for approximately equal numbers of patients who underwent such testing (Cohort 1; n=26) or did not (Cohort 2; n=25).
    Results: Across most time points, failure and warning signs by molecular testing were not significantly more frequent in patients who did or did not undergo BCR::ABL1 mutational profiling. Conversely, similar frequencies of optimal milestones were observed in patients with or without testing. Patients who underwent BCR::ABL1 mutational profiling were more likely to have splenomegaly (p=0.0069) versus those who did not.
    Conclusion: There were few significant differences in failure and warning signs by molecular testing in patients who did or did not undergo mutational profiling. Patients who underwent BCR::ABL1 mutational profiling were significantly more likely to have splenomegaly, which is not included in consensus guidelines as a reason to conduct such testing. Taken together, these findings raise potential concerns about consensus guideline adherence as a means to optimize CML management for TKI resistance.
    Keywords:  BCR::ABL1; chronic myeloid leukemia; mutation; review; treatment resistance; tyrosine kinase inhibitors
    DOI:  https://doi.org/10.21873/cdp.10518
  7. Int J Hematol. 2026 Mar 01.
    Five-year interim analysis of J-SKI: an observational study of TKI discontinuation in patients with CML in Japan.
    Naoto Takahashi, Shinya Kimura, Eri Matsuki, Takaaki Ono, Noriko Doki, Masaki Iino, Masashi Sawa, Yoshio Saburi, Kazunori Murai, Katsumichi Fujimaki, Shingo Kurahashi, Noriyoshi Iriyama, Takashi Onaka, Emiko Sakaida, Chikashi Yoshida, Keijiro Sato, Toshihiro Miyamoto, Tomoiku Takaku, Motoaki Shiratsuchi, Fumihiko Kimura, Seiichiro Katagiri, Matsuo Yamamoto, Akiko M Saito, Hitoshi Kiyoi, Itaru Matsumura.
      Treatment-free remission (TFR) is an emerging goal for patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI). However, long-term TFR durability in real-world settings remains understudied. The J-SKI study, a large observational study, was conducted to evaluate long-term TFR outcomes in Japanese patients with CML. This interim analysis included 795 eligible patients from the prospective (n = 283) and retrospective (n = 512) cohorts. With a median follow-up of 32 months (range 0.8-168) after TKI discontinuation, the 5-year TFR rate was 65.2% (95% confidence interval [CI]: 59.6-70.6%). Among patients who experienced molecular relapse, 99% (95% CI: 97-100%) regained a major molecular response after resuming TKI therapy, with no observed disease progression. Multivariate analysis identified the duration of deep molecular response (DMR) as the sole independent predictor of successful TFR, with each additional year of DMR reducing the relapse risk by 12.5% (HR: 0.875, p < 0.0001). A second TFR attempt was successful in 41% (95% CI: 22-59%) of the 32 patients. This study demonstrated that TKI discontinuation is a safe and feasible strategy in a real-world clinical setting. A sustained DMR is critical for TFR success, supporting its importance as a key therapeutic objective.
    Keywords:  Chronic myeloid leukemia; Deep molecular response; Treatment-free remission; Tyrosine kinase inhibitor
    DOI:  https://doi.org/10.1007/s12185-026-04184-4
  8. Haematologica. 2026 Mar 05.
    Epcoritamab plus rituximab, dexamethasone, cytarabine, oxaliplatin/carboplatin induces deep and durable responses in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma: results from the EPCORE NHL-2 trial.
    Pau Abrisqueta, Yasmin H Karimi, Daniel Morillo, Raúl Cordoba, Tycel Phillips, Sven De Vos, Marcel Nijland, Fritz Offner, Per-Ola Andersson, Joshua Brody, Chan Y Cheah, Pilar Gomez Prieto, Mats Hellström, Judit Meszaros Jørgensen, David Lewis, Kim M Linton, Gerardo Musuraca, Liwei Wang, Jennifer Marek, Kojo Osei-Bonsu, Malene Risum, Lorenzo Falchi.
      The treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains challenging, with inadequate responses to salvage chemoimmunotherapy limiting patients' ability to receive potentially curative treatments like autologous stem cell transplantation (ASCT). Epcoritamab, a subcutaneous CD3×CD20 bispecific antibody, has demonstrated antitumor activity in R/R DLBCL as a monotherapy and in combination with chemotherapy. In Arm 4 of the EPCORE® NHL-2 phase 1b/2 trial (NCT04663347), transplant-eligible patients with CD20+ R/R DLBCL received epcoritamab plus rituximab, dexamethasone, cytarabine, oxaliplatin/carboplatin (R-DHAX/C). Patients could continue epcoritamab until ASCT or progression. Twenty-nine patients received epcoritamab plus R-DHAX/C; 72% had stage IV disease; 66% had primary refractory disease. As of January 15, 2025 (median follow-up 40.4 months), overall response rate (primary endpoint) was 79%, and complete response rate was 69%. Sixteen patients (55%) proceeded to ASCT and five remained on epcoritamab monotherapy. At 36 months, an estimated 70% of responses were ongoing, 59% of patients were progression-free, and 76% were alive. Common treatment-emergent adverse events (TEAE) were thrombocytopenia (90%), anemia (66%), and neutropenia (59%). Cytokine release syndrome occurred in 45% of patients; all were grade 1-2 and resolved after a median of 2 days. Immune effector cell-associated neurotoxicity syndrome occurred in one patient. No fatal TEAE or clinical tumor lysis syndrome were observed. Epcoritamab plus R-DHAX/C achieved deep, durable responses with manageable safety. Over half of patients proceeded to ASCT, a potentially curative treatment. These findings suggest the potential of epcoritamab combined with standard chemoimmunotherapy as an effective salvage treatment for patients with R/R DLBCL.
    DOI:  https://doi.org/10.3324/haematol.2025.300086
  9. J Neurooncol. 2026 Mar 02. pii: 26. [Epub ahead of print]177(1):
    Real-world comparison of BTK inhibitors and lenalidomide as first-line maintenance in primary CNS lymphoma: a multi-center retrospective study.
    Xiaoli Chang, Zhangyuting He, Huanyuan Wang, Huiying Zhu, Yixian Guo, Dongmei Zou, Zhilian Zhao, Tianbin Song, Ronghua Hu, Jing Ni, Hong Zhao, Wuhan Hui, Zixian Liu, Zhenling Li, Wei Zhang, Daobin Zhou, Yan Zhang, Wanling Sun.
       BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive malignancy presenting significant therapeutic challenges. Optimal maintenance therapy following initial remission remained debated.
    METHODS: We conducted a multicentre, real-world study comparing BTK inhibitors (BTKi, n = 23) versus lenalidomide (n = 48) as maintenance in 71 newly diagnosed PCNSL patients in remission.
    RESULTS: With a median follow-up of 41.2 months, median overall survival (OS) and progression-free survival (PFS) remained unachieved for the total cohort. BTKi maintenance was associated with significantly superior PFS compared with lenalidomide (not achieved vs. 61.0 months; p = 0.016), with a substantially higher 6-year PFS rate (91.3% [95% CI: 69.5-97.7%] vs. 41.5% [95% CI: 23.8-58.4%], P < 0.001). This benefit was confirmed as an independent favourable prognostic factor in multivariate analysis (HR = 0.22, 95% CI: 0.05-0.87; P = 0.036). While PFS differed significantly, OS was comparable between the two groups. It is notable that 86.4% of patients who relapsed during lenalidomide maintenance transitioned to BTKi-based regimens, achieving a substantial second-line PFS (median 20.5 months). Furthermore, BTKi benefit was stable regardless of maintenance duration. In contrast, lenalidomide maintenance showed significant heterogeneity: optimal cutoffs for duration were identified separately for PFS (21.3 months) and OS (6.3 months). No treatment-related deaths occurred.
    CONCLUSION: These data suggest that BTKi maintenance is a highly effective strategy for newly diagnosed PCNSL, offering prolonged progression-free survival compared with lenalidomide. The significant efficacy of BTKi in both first-line maintenance and second-line salvage settings provides a preliminary basis for re-evaluating current treatment paradigms, pending confirmation by prospective trials.
    Keywords:  BTK inhibitors; Efficacy; Lenalidomide; Maintenance therapy; Primary central nervous system lymphoma
    DOI:  https://doi.org/10.1007/s11060-026-05492-9
  10. Blood. 2026 Mar 05. 147(10): 1010-1011
    Targeting BCMA: a double-edged sword for infection risk.
    Carlos Fernández de Larrea.
      
    DOI:  https://doi.org/10.1182/blood.2025032329
  11. Blood Adv. 2026 Mar 03. pii: bloodadvances.2025018720. [Epub ahead of print]
    Sintilimab, pegaspargase, and anlotinib as induction therapy for advanced-stage NKTCL: a multicenter phase II study.
    Dahui Li, Chuanxu Liu, Jiangbo Wan, Wenhao Zhang, Yujie Ma, Yang Zhu, Liyuan Ma, Shu Tian, Hao Ding, Rong Tao.
      Extranodal natural killer/T-cell lymphoma is an aggressive Epstein-Barr virus-associated lymphoma with poor outcomes in advanced-stage disease. High-dose methotrexate-containing, asparaginase-based regimens induce responses but are limited by toxicity, and lower-intensity alternatives show suboptimal durability. We conducted a prospective, multicenter, single-arm phase II trial of the LEAP regimen in newly diagnosed stage IV disease. Eligible patients had ECOG 0-3 and were >65 years or ≤65 years with contraindications to high-dose methotrexate. Treatment comprised up to eight 21-day cycles of sintilimab 200 mg (day 1), pegaspargase 2500 IU/m2 (day 1), and anlotinib 8 mg (days 1-14), with autologous hematopoietic stem cell transplantation (auto-HSCT) allowed for complete responders at the investigator's discretion and patient's preference. Thirty-seven patients were enrolled (median age 64; range, 32-78). At week 24, the complete remission (CR) was 72.9% (27/37), surpassing the prespecified 55% threshold. With a median follow-up of 48 months, estimated 4-year progression-free survival (PFS) and overall survival (OS) were 56.6% and 75.2%, respectively. Seventeen patients underwent auto-HSCT after achieving CR and had lower relapse (17.6% vs 60.0%) and improved PFS (Hazard Ratio=0.23; p<0.05) versus observation. Grade ≥3 adverse events were limited to neutropenia (10.8%) and hyperbilirubinemia (10.8%), with no treatment discontinuations for toxicity or treatment-related deaths. LEAP regimen produced high CR rates and durable survival with manageable toxicity in advanced-stage disease unsuitable for HD-MTX induction and may enable curative-intent therapy; randomized validation is warranted. The study was registered at ClinicalTrials.gov (NCT04004572).
    DOI:  https://doi.org/10.1182/bloodadvances.2025018720
  12. Blood. 2026 Mar 04. pii: blood.2025031016. [Epub ahead of print]
    Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement and Pemigatinib.
    Alessandro M Vannucchi, Jay L Patel, Jean-Jacques Kiladjian.
      Myeloid/Lymphoid neoplasms with FGFR1 rearrangement (M/LN-FGFR1) are rare, heterogenous diseases due to fusion transcripts originated by translocations of FGFR1 with different partners, resulting in constitutive FGFR1-mediated signaling. Presentation varies from chronic myeloid neoplasms to acute leukemia or lymphoma and extramedullary localizations are common. Outside allogeneic stem cell transplantation (ASCT), survival with conventional therapy is dismal, representing an unmet clinical need. We summarize here the data that led to approval of pemigatinib, a FGFR1 inhibitor, showing unprecedented efficacy in M/LN-FGFR1.
    DOI:  https://doi.org/10.1182/blood.2025031016
  13. Blood. 2026 Mar 05. pii: blood.2025031366. [Epub ahead of print]
    Genomic profiling for decision-making in post-polycythemia vera and post-essential thrombocythemia myelofibrosis.
    Barbara Mora, Francesca Palandri, Paola Guglielmelli, Andrew T Kuykendall, Margherita Maffioli, Alessandra Iurlo, Valerio De Stefano, Silvia Salmoiraghi, Timothy Devos, Federico Itri, Francisco Cervantes, Jean-Jacques Kiladjian, Matteo G Della Porta, Francesco Albano, Jason Gotlib, Giulia Benevolo, Marianna Caramella, Marco Ruggeri, Elisa Rumi, David M Ross, Chiara Pessina, Ilaria Colugnat, Francesco Orsini, Giorgia Micucci, Giada Rotunno, Rami S Komrokji, Daniele Cattaneo, Patrizia Chiusolo, Marta Bortolotti, Tiziano Barbui, Daniela Cilloni, Massimo Breccia, Giuseppe A Palumbo, Filippo Branzanti, Ludovica Margotto, Matteo Franchi, Alessandro M Vannucchi, Francesco Passamonti.
      Secondary myelofibrosis (SMF) represents a late stage of polycythemia vera and essential thrombocythemia, with overall survival (OS) currently defined by the MYelofibrosis SECondary to PV and ET (MYSEC) Prognostic Model (MYSEC-PM). To identify additional myeloid neoplasm-associated cancer gene variants (CGVs) associated with SMF outcome, we evaluated next-generation sequencing panel testing in 644 patients within the MYSEC cohort. Overall, 429 (66.6%) subjects reported at least one CGV, with ASXL1, TET2 and DNMT3A being the most frequently involved. Specific molecular profiles affected OS (p < .001): U2AF1, TP53 or SRSF2 variants (UTS, 9.3% of cases, median OS 4.1 years) and ASXL1 without UTS (25.3%, median OS 8.4 years). By integrating these genetic signatures within the MYSEC-PM through penalized Cox regressions, we identified the following independent predictors (p from < .0001 to .02) and weighted: hemoglobin <11 g/dl (1 point), circulating blasts ⩾3% (2), platelets <150 × 109/l (2), age (0.21 points/year), ASXL1 without UTS mutations (1) and any UTS mutations (3). Finally, we developed the MYSEC-molecular prognostic model (MYSEC-mPM) allocating 582 SMF patients into four categories with different OS (p < .001): low (median OS 18.0 years, 95%CI: 14.2-not reached; score <14), intermediate-1 (8.8. years, 95%CI: 7.7-9.7; score 14-16), intermediate-2 (4.6 years, 95%CI: 3.1-7.2; score 17-18), and high risk (1.9 years, 95%CI: 1.2-2.5; score ⩾19). Additionally, in 381 SMF with available cytogenetics, the MYSEC-mPM was implemented with complex/monosomal karyotype, generating the karyotype-enhanced MYSEC-kmPM. Our study shows that genomic and cytogenetic profiling improve survival prediction in SMF, outperforming the MYSEC-PM.
    DOI:  https://doi.org/10.1182/blood.2025031366
  14. Blood. 2026 Mar 05. 147(10): 1008-1010
    Could a TCR be faster than a CAR?
    Fateeha Furqan, Paolo Strati.
      
    DOI:  https://doi.org/10.1182/blood.2025031787
  15. Blood Adv. 2026 Mar 05. pii: bloodadvances.2025018706. [Epub ahead of print]
    Selinexor plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: a multicenter, open-label, phase 1 study.
    Haris Ali, Sanjay Ram Mohan, Ashwin Kishtagari, Josef T Prchal, Keri Renee Maher, Yi Chai, Girish Gudi, Pietro Taverna, Tomer Martin Mark, Srinivas K Tantravahi.
      The phase 1 portion of SENTRY/XPORT-MF-034 (NCT04562389) evaluated the exportin 1 inhibitor selinexor (40 mg/60 mg once weekly) plus ruxolitinib in patients with JAK inhibitor-naïve myelofibrosis (n = 24). Primary endpoints were maximum tolerated selinexor dose, recommended clinical trial dose, and safety. No dose-limiting toxicities were reported. Common adverse events were nausea, fatigue, anemia, thrombocytopenia, constipation, vomiting, and headache. Nausea was transient, mainly grade 1, and managed by prophylactic antiemetics. Four deaths occurred, all unrelated to study treatment. Selinexor 60 mg in combination with ruxolitinib was identified as the recommended phase 3 dose based on safety, efficacy, and exposure-response analyses. Overall safety profiles and grades of clinically significant adverse events were similar and generally manageable regardless of selinexor dose. A greater proportion of patients achieved spleen volume reduction equal to or greater than 35% (SVR35) and total symptom score reduction equal to or greater than 50% (TSS50) at Week 24 in the 60-mg selinexor group (79% and 58%) compared with the 40-mg group (38% and 25%). Among evaluable patients who received suboptimal ruxolitinib ≤5 mg twice-daily in the selinexor 60-mg group, SVR35 was observed in 100% (6/6) of patients and TSS50 was observed in 75% (3/4) of patients.
    DOI:  https://doi.org/10.1182/bloodadvances.2025018706
  16. Haematologica. 2026 Mar 05.
    Proteostasis meets signaling: UBE2G1 in hematopoietic stem cell aging.
    Vika Miller, Boaz Nachmias.
      
    DOI:  https://doi.org/10.3324/haematol.2026.300724
  17. Blood. 2026 Mar 02. pii: blood.2025030630. [Epub ahead of print]
    Fixed-duration VenO vs FCR/BR in fit patients with untreated CLL: primary analysis of the phase 3 CRISTALLO trial.
    Jeff P Sharman, Luca Laurenti, Emmanuelle France Ferrant, Luis Felipe Casado Montero, Stephen P Mulligan, Rosemary Anne Harrup, Stephen S Opat, Adalberto Ibatici, Roberto Marasca, Paolo Sportoletti, Maria Thadani-Mulero, Oscar Cazares, Weize Huang, Yanwen Jiang, Emma Clark, Hyun Yong Jin, Michelle Boyer, Franck Morschhauser.
      The phase 3 CRISTALLO trial (NCT04285567) compared first-line fixed-duration venetoclax-obinutuzumab (VenO) vs fludarabine, cyclophosphamide, and rituximab (FCR)/bendamustine-rituximab (BR) in patients with chronic lymphocytic leukemia, using undetectable minimal residual disease (uMRD) as the sole primary endpoint. Previously untreated patients with a cumulative illness rating scale score ≤6, creatinine clearance ≥70 mL/min, without del(17p)/TP53 mutations were randomized 1:1 to VenO or FCR/BR. The primary endpoint was uMRD (<10-4) in peripheral blood (PB) using next-generation sequencing at month 15. Key secondary endpoints included uMRD (<10-4) in PB and bone marrow (BM) at end of treatment (EOT), and progression-free survival (PFS). uMRD at deeper cutoffs were explored. At data cutoff (March 19, 2024), 80 patients received VenO and 86 received FCR/BR. Baseline characteristics were generally balanced across arms. The primary endpoint was met: 81.3% (VenO) and 54.7% (FCR/BR) achieved uMRD (<10-4) in PB at month 15 (P = .0004). uMRD (<10-4) in PB and BM at EOT was also higher with VenO vs FCR/BR. Short follow-up precluded evaluation of PFS at the first planned interim analysis; however, fewer patients progressed/died with VenO vs FCR/BR (7 vs 13). At month 15, 65.0% (VenO) and 25.6% (FCR/BR) achieved uMRD (<10-6) in PB. The overall safety profile was consistent with the known safety profile of each drug. No patient in the VenO arm was deemed high-risk for tumor lysis syndrome following obinutuzumab debulking; no clinical TLS occurred. These results confirm and extend the findings from the GAIA-CLL13 trial, validating increased depth of response with VenO vs chemoimmunotherapies.
    DOI:  https://doi.org/10.1182/blood.2025030630
  18. Future Oncol. 2026 Mar;22(6): 643-658
    Odronextamab in people with relapsed or refractory follicular lymphoma: plain language summary of the ELM-2 study.
    Jose C Villasboas, Michelle Poon, Monica Tani, Ana Jiménez-Ubieto, Benoit Tessoulin, Lorna Warwick, Deborah Brown, Manjusha Namuduri, Chinjune Lin, Virginie Delwart, Deepa Jagadeesh.
      
    Keywords:  Bispecific antibody; Clinical trial; Follicular lymphoma; Hematologic/Lymphoma; Non-Hodgkin's lymphoma; Odronextamab; Phase 2; Plain language summary
    DOI:  https://doi.org/10.1080/14796694.2026.2628111
  19. Blood. 2026 Mar 05. 147(10): 1007-1008
    Ready, set, GO? Treating older adults with AML.
    Wei-Ying Jen, Farhad Ravandi.
      
    DOI:  https://doi.org/10.1182/blood.2025032119
  20. Int J Hematol. 2026 Mar 01.
    Acute diplopia caused by extramedullary multiple myeloma.
    Yusuke Okamoto, Sho Koyasu, Akifumi Takaori-Kondo.
      
    DOI:  https://doi.org/10.1007/s12185-026-04183-5
  21. Ann Hematol. 2026 Mar 06. pii: 163. [Epub ahead of print]105(4):
    Reduced dose versus standard melphalan conditioning for autologous stem cell transplantation in multiple myeloma: a single-center retrospective study.
    Yifan Yao, Shan Zhang, Ziying Li, Lili Luo, Xuan Lu, Huafang Wang.
      
    Keywords:  Autologous stem cell transplantation; Dose reduction; Melphalan; Multiple myeloma
    DOI:  https://doi.org/10.1007/s00277-026-06909-1
  22. Blood. 2026 Mar 02. pii: blood.2025031897. [Epub ahead of print]
    TCR T cells targeting IgA- and IgG-expressing multiple myeloma.
    Karolos Douvlataniotis, Aleksei Titov, Julia Zeun, Merve Bilici, Heyilimu Palashati, Waywen Loh, Even Holth Rustad, Weiwen Yang, Trung T Tran, Fridtjof Lund-Johansen, Ravi Chand Bollineni, Jessica D Kepple, Luis P Huth, Ludvig A Munthe, Thorstein Boxaspen, Fredrik Schjesvold, Anders Waage, Dimitrios L Wagner, Katherine R Bull, Joanna Hester, Fadi Issa, Eirini Giannakopoulou, Johanna Olweus.
      T cell-based therapies have shown remarkable efficacy in multiple myeloma (MM), yet the disease remains largely incurable. Here, we investigated the constant domains of the immunoglobulin heavy chain (IgH) as novel targets for therapeutic T cell receptors (TCRs), after confirming high and homogeneous IGH expression in >95% of MM patients. MM cells secrete excessive monoclonal immunoglobulins (M-proteins) that drive complications but are inaccessible to CAR T-cell or antibody targeting. Peptides from IgA and IgG constant regions were eluted from HLA-A*02:01, and reactive TCRs were isolated from healthy donors using allo-HLA-A*02:01 presentation to circumvent self-tolerance. T cells engineered with two TCRs specific for IgA or IgG passed a stringent multi-tier safety screen and selectively eliminated MM cells from 20 HLA-A*02:01+ patients secreting the relevant IgH in vitro. In vivo, IgA-TCR T cells eradicated IgA+HLA-A*02:01+ MM cells in xenograft models and reduced circulating IgA in humanized mice. These findings establish immunoglobulin constant domains as viable TCR targets in MM, potentially making ~40% of patients of European descent eligible for TCR T cell therapy, and extension to additional HLA alleles could further broaden eligibility. The approach may also be applicable to lymphoma and antibody-mediated autoimmune diseases.
    DOI:  https://doi.org/10.1182/blood.2025031897
  23. Blood. 2026 Mar 05. 147(10): 1005-1006
    Introduction to a review series on hemophagocytic lymphohistiocytosis.
    Helen E Heslop, Jorge Di Paola.
      
    DOI:  https://doi.org/10.1182/blood.2025032749
  24. Blood. 2026 Mar 02. pii: blood.2025030791. [Epub ahead of print]
    Thrombotic thrombocytopenic purpura: celebrating 25 years of ADAMTS13.
    Marie Scully, Matthew A Carter, Maryam Owais Subhan.
      Thrombotic Thrombocytopenic Purpura (TTP) was first described just over a century ago and it is now 25 years since the identification of ADAMTS13 as the enzyme deficient in both antibody-mediated immune TTP and congenital TTP. The discovery of ADAMTS13 has been fundamental to the vast improvement seen in TTP outcomes. Understanding the interaction between ADAMTS13, platelets and vWF led to development of clinical ADAMTS13 assays and therefore quicker and accurate diagnosis, but also, critically, to novel therapies and monitoring of treatment. Landmark additions to immune TTP therapy have included anti-CD20 treatment with rituximab, in both the acute and elective setting and the use of the nanobody caplacizumab in acute TTP. In congenital TTP, the use of ADAMTS13 replacement is playing a role in reducing end-organ damage and morbidity, with recombinant ADAMTS13 now representing the gold standard for cTTP. The ability to measure response to treatment by monitoring ADAMTS13 activity has underpinned these treatment advances and allowed clinicians to tailor immunosuppressive treatment for iTTP and rADAMTS13 dosing in cTTP. Looking forward, there are many avenues for future development with potential expansion of recombinant ADAMTS13 to treat immune TTP, new, quicker assays to improve diagnosis, monitoring and immunomodulatory therapeutic advancement, all underpinned by ADAMTS13. Future endeavors for the role of ADAMTS13 in other thrombotic indications opens further exciting opportunities.
    DOI:  https://doi.org/10.1182/blood.2025030791
  25. Cancer Control. 2026 Jan-Dec;33:33 10732748261432266
    The Changing Landscape of Second Primary Malignancies in Multiple Myeloma: A SEER Population-Based Study Between Two Therapeutic Eras.
    Weixiang Lu, Xiaoshan Huang, Shengyu Tian, Xiaojie Liang, Guanzhou Ke, Jia Guo, Qingqing Li, Yuquan Huang, Yang Li, Baiwei Luo, Bingyu Lin, Dan Xu, Liang Wang.
      IntroductionThe introduction of proteasome inhibitors and immunomodulatory agents has significantly improved the prognosis of multiple myeloma (MM). However, the occurrence of second primary malignancies (SPMs) in MM survivors has raised widespread concern.MethodsThis population-based retrospective study using the SEER database analyzed data from 26,869 MM patients (1990-2021) to evaluate changes in SPMs across two therapeutic eras. Patients were stratified into two therapeutic eras based on the year of MM diagnosis: Era-1 (1990-2005; n=12,858) and Era-2 (2006-2021; n=14,011).ResultsAmong 1,346 MM patients who developed SPMs, 670 were in Era-1 and 676 in Era-2. The 15-year cumulative incidence of SPMs was significantly higher in Era-2 (7.7% vs. 4.8%, P < 0.001), an increase driven mainly by solid tumors (6.90% vs. 4.10%, P < 0.001) with no significant change in second hematological malignancies (0.84% vs. 0.67%, P = 0.13). Standardized incidence ratio (SIR) analysis revealed elevated hematological malignancy risk in Era-2 (SIR = 1.71, 95% CI: 1.49-1.96). Median time to SPM was shorter in Era-2 (43.5 vs. 59 months, P < 0.001). Notably, 80% of SPMs in Era-2 occurred within 90 months of MM diagnosis. Overall survival (OS) of SPM patients showed no significant improvement in Era-2 compared to Era-1. Within each diagnostic era, patients who developed SPMs exhibited longer overall survival than those with MM alone; however, this reflects survivor bias, as SPMs can only develop in patients who survive long enough after the initial MM diagnosis. No significant OS differences were observed among SPM patients by race or gender.ConclusionsThe risk of SPMs in MM survivors has significantly increased, and the latency between MM diagnosis and the onset of SPMs was shorter in the Era-2, highlighting the need for enhanced cancer surveillance in MM survivors.
    Keywords:  cumulative incidence; multiple myeloma; prognosis; second primary malignancies; therapeutic era
    DOI:  https://doi.org/10.1177/10732748261432266
  26. Haematologica. 2026 Mar 05.
    REALiTEC: a multi-country observational retrospective study of teclistamab in patients with relapsed/refractory multiple myeloma outside of clinical trials.
    Katarina Uttervall, Martin K Kortum, Aurore Perrot, Sarah Leeth Farmer, Michele Cavo, Bhuvan Kishore, Caroline Jacquet, Maria Casanova, Markus Hansson, Katja Weisel, Hila Magen, Carmine Liberatore, Charlotte Toftmann Hansen, Moshe E Gatt, Tamir Shragai, Matteo Claudio Da Via, Teresa De Soto Alvarez, Mathew Streetly, Marc S Raab, Salomon Manier, Jesper Aegesen, Claire Albrecht, Peter Hu, Pavel Smirnov, Diptendu Santra, Eva Rubio-Azpeitia, Rakesh Popat.
      Teclistamab is the first approved anti-BCMA bispecific antibody for patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM), based on the results of MajesTEC-1 clinical trial. Here, we first report the findings from REALiTEC, a retrospective observational study of patients who received teclistamab outside of clinical trials in Europe and Israel. The study included 113 patients from 23 sites in eight countries, with most (88.5%) accessing the medication through pre-approval access programs. The median age was 66 years, and patients had a median of 6 prior lines of therapy. Notably, 78.8% were triple-class refractory, 44.2% penta-class refractory, and 35.4% had previous anti-BCMA treatment. Overall response rate (ORR) was 60.2%, with 52.2% of patients achieving a very good partial response or better (≥VGPR). After a median follow-up of 20.7 months, median duration of response (DoR) was 20.3 months, median progression-free survival (PFS) was 9.7 months, and median overall survival (OS) was 26.3 months. Patients attaining ≥VGPR experienced longer DOR (median 26.1 months), with 12-month PFS and OS rates of 71.2% and 83.1%, respectively. Subgroup analyses demonstrated consistent outcomes across different patient groups, even in those with historically poorer outcomes. Most common adverse events were infections (all grade: 70.8%), cytokine release syndrome (55.8%), neutropenia (35.4%), and anaemia (25.7%), with no new safety signals identified. Infection rates decreased over time, and immunoglobulin replacement therapy was used in up to 60% of patients. REALiTEC corroborates the efficacy observed in MajesTEC-1, supporting teclistamab as an effective treatment option in heavily pre-treated RRMM patients.
    DOI:  https://doi.org/10.3324/haematol.2025.289281
  27. Blood Adv. 2026 Mar 04. pii: bloodadvances.2025019152. [Epub ahead of print]
    Low Serum Cholesterol Is a Biomarker of Advanced Disease and Poor Outcomes in Myeloproliferative Neoplasms.
    Orly Leiva, Steven Soo, Olivia C Liu, Victor You, Andrew Stephen Palmer, Justin Abraham Kahla, Yasmeen Murtaza, Olatoyosi Odenike, Anand A Patel, Jeanne DeCara, Patrycja M Dubielecka, Max Petersen, Michelle H Lee, Joan How, Gabriela S Hobbs.
      Myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are a diverse group of hematopoietic stem cell neoplasms associated with an increased risk of hematologic progression to secondary MF or leukemia and cardiovascular disease (CVD). Elevated total cholesterol levels are traditional CVD risk factors. Patients with MPNs may have reduced cholesterol levels, potentially reflecting an underlying hypermetabolic state. The impact of serum total cholesterol on clinical outcomes in patients with MPNs has not yet been evaluated. We performed a multicenter retrospective cohort study of patients with MPNs who had undergone transthoracic echocardiography (TTE) with available serum lipid levels at time of TTE not on statin therapy. Patients were categorized by total cholesterol level (≥ 150, 120 - 149, and < 120 mg/dL). Outcomes evaluated were MPN disease progression to secondary MF or acute leukemia, major adverse cardiovascular events (MACE), and death. Multivariable competing-risk regression modeling was performed. A total of 305 patients were included of whom 54.4% had total cholesterol ≥ 150, 21.3% 120 - 149, and 24.3% < 120 mg/dL. After a median follow-up of 50.8 months, total cholesterol < 120 was associated with increased risk of MPN disease progression (aSHR 3.00, 95% CI 1.36 - 6.63), heart failure hospitalization (aSHR 3.76, 95% CI 1.77 - 7.96), and all-cause death (aHR 1.87, 95% CI 1.06 - 3.30) vs ≥ 150 mg/dL. Among patients with MPN, low total cholesterol levels were associated with increased risk of MPN disease progression.
    DOI:  https://doi.org/10.1182/bloodadvances.2025019152
This page is being maintained by Thomas Krichel. It was last updated on 2026‒03‒15 at 11:41.