bims-hemali 2026-03-29 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2026–03–29
thirty-two papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Tyrosine kinase inhibitors, chronic myeloid leukemia, and pregnancy: pharmacotherapeutic challenges and recommendations.
Safety and Efficacy of Flumatinib in Patients with Chronic Phase Chronic Myeloid Leukemia: A Real-Life Cohort Observational Study.
Activated Memory Cytotoxic T-Lymphocytes and T-Cell Receptor Vβ Clonality Predict Treatment-Free Remission After Tyrosine Kinase Inhibitor Discontinuation in Chronic-Phase Chronic Myeloid Leukemia: A 1-Year Prospective Immuno-Monitoring Study.
A phase I/II Study of Duvelisib plus Venetoclax in Patients with Relapsed/Refractory CLL/SLL or Richter Transformation.
Beyond ATP: asciminib and the allosteric path in CML.
Ruxolitinib treatment in patients with polycythemia vera reduces JAK2 variant allele frequency and improves symptom burden and hematocrit control.
Outcomes of Patients Treated With Dasatinib 50 mg/d: A Pooled Analysis.
Marginal Zone Lymphoma: 2026 Update on Diagnosis and Management.
Myeloproliferative neoplasms with concomitant chronic myeloid leukemia are associated with TKI resistance and poor outcomes.
Are We Moving Toward Curative Approaches in Chronic Lymphocytic Leukemia?
Ropeginterferon alfa-2b for pre-fibrotic myelofibrosis and lower-risk myelofibrosis requiring cytoreduction.
Prognosis and treatment of plasmablastic lymphoma in the United States: a multicenter retrospective study.
Dual-specificity phosphatase 21 enhances the sensitivity of imatinib-resistant chronic myeloid leukemia cells to ponatinib through GATA-1-mediated erythroid differentiation.
The Glucose and Glutamine Requirements of Cancer and Normal Cells Do Not Distinguish Them, in Contrast to Their Methionine Requirement, Suggesting the Warburg Effect Is Not a Cancer Paradigm.
Ronceray L, Huibers MHW, Reutter K, et al. High-grade/large B-cell lymphoma-11q has a very good prognosis in children and young people without a predisposition. Blood. 2026;147(2):209-214.
Maintenance Strategies in High-Risk Myeloma: A Multicenter Comparison of Bortezomib-Lenalidomide Versus Lenalidomide Alone: A USMIRC Multicenter Analysis.
IGH::FENDRR and specific KRAS mutations define a novel B-ALL molecular subtype with poor chemotherapy response.
Targeting Mitochondrial Vulnerabilities in Chronic Myeloid Leukemia: From Pathobiology to Novel Therapeutic Opportunities.
From Breakthroughs to Blueprints: Evolving Evidence and Future Directions in Relapsed and Refractory Large B-Cell Lymphoma.
Disrupting adaptive proteostasis to overcome proteasome inhibitor resistance.
[Follicular and follicle center-cell lymphomas: A family between kinship and diversity].
From Molecular Silence to Lymphoid Blast Phase: Diagnostic and Therapeutic Challenges in a Young Female Patient With Chronic Myeloid Leukemia.
A new era for heavy menstrual bleeding.
Primary central nervous system lymphoma: Evolving treatment strategies to achieve improved long-term disease control.
Combination of mitoxantrone hydrochloride liposome with cyclophosphamide, vincristine, and prednisone for patients with treatment-naive peripheral T-cell lymphoma: A multicenter, open-label, single-arm, phase 1b trial.
Treatment-free Remission in Chronic Myeloid Leukemia in Low- and Middle-Income Countries.
Management of relapsed/ refractory AL amyloidosis.
Survival after intensive therapy or clofarabine in fit older adults with acute myeloid leukemia: E2906 phase 3 trial.
Final clinical data of a phase 1 dose-escalation study of WVT078, a BCMA×CD3 bispecific antibody, alone and in combination with γ-secretase inhibitor WHG626 in patients with relapsed and/or refractory multiple myeloma.
Vitamin D receptor expression in germinal centre type diffuse large B-cell lymphoma cells is associated with vitamin D insensitivity.
Masquerading as an Interstitial Lung Disease: Intravascular Large B-Cell Lymphoma With Prominent Neo-Angiogenesis.
Assessment of flonoltinib maleate versus ruxolitinib phosphate in intermediate- to high-risk myelofibrosis (FMF-02): study protocol for a multicenter, randomized, open-label phase IIB trial.

Expert Opin Pharmacother. 2026 Mar 26. 1-8

Tyrosine kinase inhibitors, chronic myeloid leukemia, and pregnancy: pharmacotherapeutic challenges and recommendations.

Fadi G Haddad, Elias Jabbour, Helen T Chifotides, Shereen Sakkal, Hagop Kantarjian.

   INTRODUCTION: The annual incidence of Philadelphia chromosome-positive chronic myeloid leukemia (CML) is 1 per 100,000 pregnancies. The management of CML during pregnancy poses challenges due to the teratogenicity risk associated with the BCR:ABL1 tyrosine kinase inhibitors (TKIs).
AREAS COVERED: In this review, we discuss the possible fetotoxicity of CML therapies during pregnancy, including TKIs and non TKI-based regimens and the treatment strategies for pregnant patients.
EXPERT OPINION: The diagnosis of CML during pregnancy is rare, and evidence guiding optimal management remains limited. Current recommendations categorize treatments into TKIs and non TKI-based therapies. All TKIs are not recommended during the first trimester due to their risk of teratogenesis, but imatinib and nilotinib may be cautiously used from Weeks 16-18 onward. Non-TKI therapies, such as hydroxyurea and interferon-α, are considered safe throughout pregnancy. Data on ponatinib and asciminib remain insufficient to allow the safe use of these agents during pregnancy. Future research should aim to improve treatment-free remission rates through novel agents and combination strategies to allow a higher proportion of younger patients to discontinue therapy. Clinicians should always counsel women on pregnancy risks during therapy while reassuring male patients of TKI safety when fathering children.

Keywords:  Chronic myeloid leukemia; imatinib; interferon-α; nilotinib; ponatinib; pregnancy; tyrosine kinase inhibitors

DOI:  https://doi.org/10.1080/14656566.2026.2651280
Blood Lymphat Cancer. 2026 ;16 573070

Safety and Efficacy of Flumatinib in Patients with Chronic Phase Chronic Myeloid Leukemia: A Real-Life Cohort Observational Study.

Fang Cheng, Zheng Cui, Qiang Li, Liu Wang, Weiming Li.

   Background: This study aims to comprehensively evaluate the safety and effectiveness of flumatinib in both first-line and subsequent-line therapies in 244 chronic-phase chronic myeloid leukemia (CML-CP) patients.
Methods: Response criteria were applied according to the European LeukemiaNet. Adverse events (AEs) occurring after flumatinib treatment were documented and graded for severity.
Results: The study encompassed 244 patients with CML-CP, stratified by treatment lines: first-line (1L, N=138), second-line (2L, N=63), and third-line or above (≥3L, N=43). First-line flumatinib therapy resulted in a major molecular response achieved by 50.7% at 6 months and 66.7% at 12 months, with a deep molecular response (DMR) achieved by 20.3% at 6 months and 35.5% at 12 months. In subsequent treatment lines, those with baseline MR2 had a DMR rate of 42.9%, compared to 23.3% for those without it. Significant differences in molecular response rates were observed based on treatment line and prior tyrosine kinase inhibitors (TKI) resistance (p<0.05). However, subgroup analyses showed no significant differences in treatment responses between the warning and resistance groups after flumatinib therapy. Dose reduction strategies, implemented in 19.3% of patients, have proven feasible without compromising efficacy. Eight patients subsequently attempted treatment cessation, with five maintaining treatment-free remission. AEs were predominantly grade 1-2, with diarrhea (27.0%), fatigue (12.3%), and thrombocytopenia (11.5%) being the most frequent. Grade 3/4 AEs were infrequent, highlighting flumatinib's manageable safety profile.
Conclusion: Flumatinib displays significant clinical efficacy and a superior safety profile compared to other second-generation TKI, whether administered in first-line or subsequent treatment settings.

Keywords:  chronic myeloid leukemia; chronic phase; clinical response; flumatinib; safety

DOI:  https://doi.org/10.2147/BLCTT.S573070
Int J Mol Sci. 2026 Mar 16. pii: 2713. [Epub ahead of print]27(6):

Activated Memory Cytotoxic T-Lymphocytes and T-Cell Receptor Vβ Clonality Predict Treatment-Free Remission After Tyrosine Kinase Inhibitor Discontinuation in Chronic-Phase Chronic Myeloid Leukemia: A 1-Year Prospective Immuno-Monitoring Study.

Tatsuro Jo, Yoshio Saburi, Taro Masunari, Kazuhiro Noguchi, Takahiro Sakai, Jun Taguchi, Eiichi Ohtsuka, Nobuo Sezaki, Ritsuko Kubota-Koketsu, Toru Kiguchi.

  We prospectively evaluated whether cytotoxic T-lymphocyte (CTL) activation and T-cell receptor (TCR) Vβ clonality predict treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) cessation in chronic-phase chronic myeloid leukemia (CML). Forty-five patients with sustained deep molecular response (DMR) were enrolled (On-TKI, n = 38; Off-TKI, n = 7) and underwent one-year immuno-monitoring from consent. The primary endpoint was 12-month TFR, defined as retention of MR4. Overall, 32/45 patients (71%) maintained TFR at 12 months. Longer TKI exposure and stable DMR were associated with TFR; notably, patients fulfilling "≥7 years of TKI plus ≥1 year of DMR" and exhibiting CTL activation features-CD8 > CD4, memory > effector, and/or highly activated CTL clones on TCR Vβ repertoire-showed the highest likelihood of durable TFR. By contrast, NK cells, effector Tregs, and G-/M-MDSCs did not discriminate TFR status in this cohort. Although antigen specificity against CML stem cells was not directly tested, the memory-dominant CTL phenotype is consistent with immune control after antigen reduction. These findings suggest that a simple, clinically accessible strategy based on flow cytometric CTL profiling and TCR Vβ clonality may help inform TKI discontinuation decisions in CML. External validation is warranted to confirm transportability and refine clinical thresholds.

Keywords:  T-cell receptor repertoire; chronic myeloid leukemia; cytotoxic T lymphocyte; deep molecular response; flow cytometry; treatment-free remission; tyrosine kinase inhibitor

DOI:  https://doi.org/10.3390/ijms27062713
Blood Adv. 2026 Mar 26. pii: bloodadvances.2025018878. [Epub ahead of print]

A phase I/II Study of Duvelisib plus Venetoclax in Patients with Relapsed/Refractory CLL/SLL or Richter Transformation.

Jennifer L Crombie, Christine E Ryan, Yue Ren, Svitlana Tyekucheva, Celeste Carey, Aaron Zou, Samantha Normilus, Josie Montegaard, Shruti Bhandari, Alvaro J Alencar, Jacob D Soumerai, Jon E Arnason, Austin I Kim, Erin M Parry, Philippe Armand, David C Fisher, Jennifer R Brown, Matthew S Davids.

In this phase I/II study, we evaluated duvelisib plus venetoclax in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and Richter Transformation (RT). Patients received duvelisib monotherapy for 1 week prior to addition of venetoclax. After 1 year of combination therapy patients with a complete response (CR) and undetectable minimal residual disease (uMRD) could discontinue therapy; patients with detectable MRD continued venetoclax monotherapy until two separate occasions of uMRD were achieved. 44 patients were enrolled: 35 with CLL/SLL and 9 with RT. CLL patient characteristics included 77% with unmutated IGHV, 46% with TP53 aberrancy, and a median of 2 prior therapies, including prior BTK inhibitor in 60%. In phase I, the maximum tolerated dose was not reached, and the recommended phase II dose was 25 mg BID duvelisib plus 400 mg daily venetoclax. 91% of patients experienced ≥grade 3 neutropenia, with febrile neutropenia in 6%. Common non-hematologic toxicities were diarrhea (63%, 14% ³grade 3), elevated aspartate aminotransferase (51%, 9% ³grade 3), and nausea (49%, 3% grade 3). The best CR and overall response rates were 60% and 91%, respectively. At cycle 13, peripheral blood and bone marrow uMRD by flow cytometry at 10-4 were 43% and 40%, respectively. The median PFS for patients with CLL/SLL was 46 months, and the 3-year PFS was 67% (95% CI: 0.51-0.86). 4 patients with RS achieved a response (3 CRs). Overall, duvelisib plus venetoclax was active in high-risk R/R CLL/SLL and RT, though serious adverse events occurred, including immune-mediated toxicities. NCT03534323.

DOI: https://doi.org/10.1182/bloodadvances.2025018878
Blood. 2026 Mar 26. 147(13): 1384-1386

Beyond ATP: asciminib and the allosteric path in CML.

Elisabetta Abruzzese.

DOI: https://doi.org/10.1182/blood.2025032327
Ther Adv Hematol. 2026 ;17 20406207261425083

Ruxolitinib treatment in patients with polycythemia vera reduces JAK2 variant allele frequency and improves symptom burden and hematocrit control.

Claire N Harrison, Jean-Jacques Kiladjian, J E Hamer-Maansson, Ahmad Naim, Francesca Palandri, Francesco Passamonti.

   Background: In RESPONSE/RESPONSE-2, ruxolitinib was superior to best available therapy (BAT) in patients with polycythemia vera (PV).
Objective: Report a post hoc pooled RESPONSE/RESPONSE-2 analysis.
Design: RESPONSE/RESPONSE-2 were randomized, open-label phase III trials. Adults with hydroxyurea-resistant/intolerant PV were randomized 1:1 to ruxolitinib or BAT; crossover to ruxolitinib was allowed after primary analysis.
Methods: JAK2V617F allele burden, hematocrit control, and Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) were assessed.
Results: Among 371 patients, mean JAK2V617F allele burden declined from baseline (ruxolitinib, 66.1%; crossover, 69.5%) through week 208 (41.4%; 37.1%). Significantly more ruxolitinib versus BAT patients achieved hematocrit control at week 28 (62.0% vs 18.2%; p < 0.0001) and ⩾50% reduction in MPN-SAF TSS at week 16 (48.7% vs 18.0%; p < 0.0001).
Conclusion: Patients receiving ruxolitinib experienced decreased JAK2V617F allele burden, durable hematocrit control, and better symptom improvements versus BAT, reinforcing ruxolitinib clinical benefit.
Trial registration: RESPONSE: https://clinicaltrials.gov/study/NCT01243944; RESPONSE-2: https://clinicaltrials.gov/study/NCT02038036.

Keywords:  Janus kinase; MPN-SAF; allele burden; myeloproliferative neoplasm; patient-reported outcome

DOI:  https://doi.org/10.1177/20406207261425083
Clin Lymphoma Myeloma Leuk. 2026 Mar 03. pii: S2152-2650(26)00063-7. [Epub ahead of print]

Outcomes of Patients Treated With Dasatinib 50 mg/d: A Pooled Analysis.

Fadi G Haddad, Elias Jabbour, Koji Sasaki, Samuel Black, Jonathan Michael Savoy, Yesid Alvarado, Gautam Borthakur, Naveen Pemmaraju, Musa Yilmaz, Sara Delasalla, Ghayas C Issa, Hagop Kantarjian.

   BACKGROUND: Dasatinib is approved at 100 mg/d for newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). We report outcomes with frontline dasatinib 50 mg/d in a large cohort of patients with CML-CP.
METHODS: In a phase II clinical trial, patients with newly diagnosed CML-CP received dasatinib 50 mg/d alone (n = 83) or in combination with venetoclax (n = 66). We evaluated the molecular response rates, incidence of adverse events, event-free survival (EFS), and overall survival (OS).
RESULTS: One hundred forty-nine patients were included; the median age at diagnosis was 46.7 years (range, 19.9-84.3); Sokal risk was high-risk in 7 patients (4.7%). By 60 months of dasatinib therapy, the cumulative rates of major molecular response, MR4, and MR4.5 were 95%, 87%, and 86%, respectively. With a median follow-up of 73 months, the 5-year EFS and OS rates were 96% and 98%, respectively. Adverse events were observed in 72 patients (48%), including pleural effusion in 19 (12.7%), of which 3 (2%) of Grade 3. Eighteen patients (12%) discontinued dasatinib due to adverse events.
CONCLUSION: The long-term follow-up confirms the safety and efficacy of dasatinib 50 mg/d in patients with newly diagnosed CML-CP.

Keywords:  Chronic myeloid leukemia; Pleural effusion; Response; Toxicity; Tyrosine kinase inhibitor

DOI:  https://doi.org/10.1016/j.clml.2026.02.013
Am J Hematol. 2026 Mar 23.

Marginal Zone Lymphoma: 2026 Update on Diagnosis and Management.

Wan Danial Noor, John F Seymour, Chan Yoon Cheah.

DISEASE OVERVIEW: Marginal zone lymphoma (MZL) is a heterogeneous group of indolent mature B-cell neoplasms with classically three major subtypes: nodal, splenic, and extranodal MZL of mucosa-associated lymphoid tissue (MALT).
DIAGNOSIS: Diagnosis and disease evaluation of MZL is further advanced by the use of genomic testing and PET/CT with emerging evidence for the use of circulating tumor DNA. The RECLASS classification system proposed a hierarchical approach to classifying MZL while the FIL-NF10 investigators introduced a fourth MZL subtype, disseminated MZL. Though the prognosis of MZL varies between subtypes and stages, the MZL IPI and FLIPI24 indices can be used for prognostication.
TREATMENT: Frontline treatment of MZL varies between localized disease and advanced-stage diseases. The former favor the use of local therapies such as radiotherapy and anti-microbial in certain subtypes with a selective role of rituximab monotherapy. The latter requires systemic immunotherapy ± chemotherapy with emerging data for cytotoxic-free and covalent Bruton tyrosine kinase inhibitor (cBTKi)-based regimens. cBTKi and immunomodulators are established in relapsed/refractory MZL, while data for antibody-drug conjugates, T-cell engagers, and potentially CAR T-cell therapies are maturing.

DOI: https://doi.org/10.1002/ajh.70289
Leukemia. 2026 Mar 27.

Myeloproliferative neoplasms with concomitant chronic myeloid leukemia are associated with TKI resistance and poor outcomes.

Laura Li Gagnon, Andrea Duminuco, Fabio Stagno, Marta Sobas, Mikhail Fominykh, Andres Virchis, Franck-Emmanuel Nicolini, Julie Hildt, Helen Bentley, Anna L Godfrey, Lee-Yung Shih, Ashlyn Chee, Adam Mead, Krzysztof Lewandowski, Patryk Sobieralski, Guy Hannah, Yasmin Reyal, Thomas Cummin, Jaroslaw Piszcz, Kawai Yip, Rebecca Frewin, Srinivasan Narayanan, Deborah Rahman, Alero Ajayi, Paul Cervi, Jennifer Byrne, Tom Taylor, Weronika Lebowa, Jiri Pavlu, Siamak Arami, Mansour Ceesay, Dominik Chraniuk, Robert Delage, Annalisa Condorelli, Clémence Santana, Deepti H Radia, Hugues de Lavallade, Dragana Milojkovic, Claire Harrison, Patrick Harrington.

Chronic myeloid leukemia (CML) and Philadelphia (Ph)-negative myeloproliferative neoplasms (MPN) are generally distinct clonal disorders, with the co-occurrence of BCR::ABL1 rearrangement with concomitant Ph-negative MPN rarely reported. Here we describe the largest known international cohort of Ph-negative MPN and coexisting CML providing important insights into this rare clinical scenario. We performed an international, multicenter, retrospective analysis of patients with concomitant BCR::ABL1 rearrangement and Ph-negative MPN, identifying 61 cases from 30 centers in 7 countries, over a 29-year period (1996-2025). Thirty-one patients (50.8%) had Ph-negative MPN preceding CML, 18 patients (29.5%) had CML preceding Ph-negative MPN, and 12 patients (19.7%) had Ph-negative MPN and CML diagnosed simultaneously. We observed increased TKI resistance and myelofibrotic transformation, especially in patients initially diagnosed with Ph-negative MPN. In this group, 35.4% (n = 11) progressed to MF, 2 patients to blast-phase MPN, and 69.2% (n = 18) failed to achieve a complete cytogenetic response. The rare e1a2 BCR::ABL1 transcript was notably prevalent which is associated with TKI resistance and a more aggressive disease course in CML. We described superior survival in those with Ph-negative MPN preceding CML, with median OS not reached, compared with 277 months for CML preceding Ph-negative MPN and 100 months for those diagnosed simultaneously (p = 0.05).

DOI: https://doi.org/10.1038/s41375-026-02928-z
Acta Medica (Hradec Kralove). 2025 ;68(4): 113-122

Are We Moving Toward Curative Approaches in Chronic Lymphocytic Leukemia?

Martin Šimkovič, Eva Vejražková, Dominika Écsiová, Pavel Vodárek.

  Over the past decade, chronic lymphocytic leukemia (CLL) management has undergone a fundamental transformation driven by the introduction of oral targeted inhibitors. Continuous Bruton tyrosine kinase (BTK) inhibition and time-limited BCL-2-based therapy has replaced chemoimmunotherapy as the standard of care, improving survival and quality of life. Ibrutinib and its next-generation analogues, acalabrutinib and zanubrutinib, provide durable disease control with improved safety. At the same time, venetoclax combined with anti-CD20 antibodies enables deep and measurable residual disease (MRD)-negative remissions within fixed-duration regimens. Recent trials have demonstrated the feasibility of MRD-guided treatment cessation and the potential benefit of combining BTK and BCL-2 inhibition to achieve durable, chemotherapy-free responses. Ongoing research focuses on optimizing treatment sequencing, overcoming acquired resistance through non-covalent BTK inhibitors, and integrating immunotherapeutic modalities such as bispecific antibodies and CAR-T cells. The current paradigm emphasizes individualized, biomarker- and comorbidity-driven therapy based primarily on TP53 and IGHV status, with treatment selection tailored to patient fitness, tolerance, and long-term safety. This review summarizes contemporary evidence, clinical practice recommendations, and future directions in the targeted management of CLL.

Keywords:  BCL2 inhibitors; BTK inhibitors; acalabrutinib; chronic lymphocytic leukemia; comorbidities; personalized medicine; targeted therapy; venetoclax

DOI:  https://doi.org/10.14712/18059694.2026.1
Blood Adv. 2026 Mar 24. pii: bloodadvances.2026019612. [Epub ahead of print]

Ropeginterferon alfa-2b for pre-fibrotic myelofibrosis and lower-risk myelofibrosis requiring cytoreduction.

Harinder Gill, Lester Au, Rita Lok Hay Yim, Paul Lee, Vivian Wing Kan Li, Lynn Chin, Qi Zhang, Po-Yan Chan, Carmen Yu Yan Lee, Tony K Y Wu, Garret M K Leung, Yok-Lam L Kwong.

There is currently no consensus on the optimal treatment for early myelofibrosis (MF). Ropeginterferon alfa-2b (ropeg) is a next-generation monopegylated interferon alfa-2b developed specifically to treat myeloproliferative neoplasms. We conducted a phase 2 study in patients with pre-fibrotic primary MF (pre-PMF), and dynamic international prognostic scoring system (DIPSS) low/intermediate-1 risk fibrotic PMF or secondary myelofibrosis (SMF), who required cytoreduction. Ongoing treatment with hydroxyurea was substituted with ropeg (week 0: 250 mcg; week 2: 350 mcg; week 4 onwards: 500 mcg every 2 weeks). The primary endpoints were safety and clinicohematological complete response (CHCR). Seventy-one patients (40 men and 31 women) with a median age of 60 (range: 31-86) years were enrolled, followed up for a median of 119 (range:10-131) weeks. At weeks 24, 48 and 104, CHCR was achieved in 63.8% (pre-PMF: 74%; fibrotic PMF: 20%; fibrotic SMF: 42.9%), 63.5% (pre-PMF: 69.6%; fibrotic PMF: 25%; SMF: 53.9%) and 70% (pre-PMF: 78.4%; fibrotic PMF: 33.3%; SMF 50%) of patients. Thrombo-hemorrhagic events were not observed after stopping hydroxyurea. At weeks 24, 48 and 104, reduction in JAK2V617F variant allele frequency (VAF) was observed in 53.1%, 70% and 67.6% of patients, and, reduction in CALR mutant VAF was observed in 52.6%, 42.9% and 40% of patients, respectively. In 50 evaluable cases at week 104, 13 patients (26%) had reduced bone marrow reticulin fibrosis. There were 3 treatment discontinuations (4.2%) due to adverse events. In conclusion, ropeg was safe and induced CHCR associated with significant molecular responses in patients with early MF. ClinicalTrials.gov Identifier: NCT04988815.

DOI: https://doi.org/10.1182/bloodadvances.2026019612
Blood Cancer J. 2026 Mar 23. pii: 43. [Epub ahead of print]16(1):

Prognosis and treatment of plasmablastic lymphoma in the United States: a multicenter retrospective study.

Matthew Hamby, Brian L Egleston, Zachary A K Frosch, Raphael E Steiner, Ariela Noy, Veronica Carvajal, Emeline R Chong, Seda S Tolu, Gaston Jean-Louis, Jennifer E Amengual, Romil Patel, Sairah Ahmed, John Sharp, Timothy Voorhees, Robert Baiocchi, Andres Ramirez-Gamero, Jorge J Castillo, Emily Hamburger, Christopher Dittus, Imran A Nizamuddin, Neha Mehta-Shah, Nyein Nyein Thaw Dar, Jose Sandoval-Sus, Alexandra E Rojek, Peter A Riedell, Niloufer Khan, Alexey Danilov, Vinod Solipuram, Paul G Rubinstein, Anthony Ariotti, Gita Suneja, Alexander Vartanov, Charles Milrod, Adam J Olszewski, Gordon Smilnak, Emily Ayers, Sahaj Desai, Joanna M Rhodes, Gabriella Magarelli, Tatyana Feldman, Meredith Pellon, David M Aboulafia, William Bae, Carlos Galvez, Vineel Bhatlapenumarthi, Mehdi Hamadani, Stefan K Barta.

Plasmablastic lymphoma (PBL) is a rare, aggressive AIDS-related lymphoma observed in patients with immunosuppressed states as well as in immunocompetent individuals. We sought to determine survival outcomes, prognostic factors, and optimal treatment regimens in a large, contemporary cohort of patients with PBL in the United States. We performed a multicenter, retrospective cohort study, including 344 patients diagnosed with PBL between 2005 and 2022. Patients were stratified into cohorts according to underlying immune status. Survival outcomes were calculated using Kaplan-Meier statistics, with cohort-specific survival outcomes adjusted using propensity score-based weighting. Factors associated with outcomes were assessed via multivariable models using multiple imputation. The median age at diagnosis was 53 years, most patients were male (n = 270), and many had HIV (n = 164). The median OS was 5.0 years, with a median PFS of 1.4 years. Patients living with HIV had the best outcomes, whereas patients with prior organ transplantation had the worst outcomes. Use of higher intensity chemotherapy regimens and use of a proteasome inhibitor in the frontline setting did not show survival benefit. While there was no clear optimal treatment approach in the frontline setting, the median OS of 5.0 years is dramatically improved compared with historical controls.

DOI: https://doi.org/10.1038/s41408-026-01457-3
Biochem Biophys Res Commun. 2026 Mar 18. pii: S0006-291X(26)00410-9. [Epub ahead of print]814 153646

Dual-specificity phosphatase 21 enhances the sensitivity of imatinib-resistant chronic myeloid leukemia cells to ponatinib through GATA-1-mediated erythroid differentiation.

Chih-Wei Chen, Yuan-Feng Lin, Yi-Yan Yeh, Nai-Kuei Huang, Huei-Mei Huang.

  BCR-ABL tyrosine kinase inhibitors (TKIs) effectively treat chronic myeloid leukemia (CML), but drug resistance remains a challenge. Inducing erythroid differentiation in CML cells to enhance their sensitivity to imatinib is a potential approach, but the key regulators are unclear. Imatinib-induced apoptosis and erythroid differentiation in CML cells are distinct processes, suggesting specific genes are involved in differentiation. Analysis of the Gene Expression Omnibus revealed that imatinib highly upregulated dual-specificity phosphatase 21 (DUSP21). A recent study showed that DUSP21 can inhibit cell proliferation. Since cell proliferation decreases during differentiation, we investigated DUSP21's role in CML cell differentiation and TKI sensitivity. Imatinib and ponatinib increased DUSP21 expression in imatinib-sensitive CML cells (K562 and BaF3/p210), whereas only ponatinib did so in imatinib-resistant cells (K562R and BaF3/T315I). DUSP21 overexpression promoted erythroid differentiation, reduced cell viability, and enhanced ponatinib-mediated growth inhibition and apoptosis in these cells. Furthermore, DUSP21 increased the expression of the erythroid transcription factor GATA-1 by activating its promoter. GATA-1 knockdown eliminated DUSP21's effects on erythroid differentiation and ponatinib sensitivity in K562 and K562R cells. Collectively, these findings suggest that DUSP21 acts as a positive regulator of erythroid differentiation in CML cells, and its overexpression sensitizes imatinib-resistant CML cells to ponatinib via GATA-1-mediated erythroid differentiation.

Keywords:  Dual-specificity phosphatase 21; Erythroid differentiation; GATA-1; Imatinib-resistant CML cells; Ponatinib

DOI:  https://doi.org/10.1016/j.bbrc.2026.153646
Anticancer Res. 2026 Apr;46(4): 1875-1882

The Glucose and Glutamine Requirements of Cancer and Normal Cells Do Not Distinguish Them, in Contrast to Their Methionine Requirement, Suggesting the Warburg Effect Is Not a Cancer Paradigm.

Yuta Miyashi, Kohei Mizuta, Tomoyuki Ishiguro, Qinghong Han, Shukuan Li, Byung Mo Kang, Jin Soo Kim, Michael Bouvet, Yasunori Tome, Kotaro Nishida, Robert M Hoffman.

   BACKGROUND/AIM: In the present study we compared the glucose and glutamine requirements of cancer and normal cells to determine if the Warburg effect is cancer specific.
MATERIALS AND METHODS: 143B human osteosarcoma, HT1080 human fibrosarcoma, HCT116 human colon cancer and normal Hs27 human fibroblasts were cultured in Dulbecco's modified Eagle's medium (DMEM) with and without glucose; with and without glutamine; or with and without methionine. The EC50 of glucose, glutamine and methionine was compared in cancer and normal cells. Co-culture of Hs27 normal fibroblast with each cancer cell line was performed by using 12-well plates with and without glucose or methionine. Cell viability was determined with the WST-8 viability reagent, by phase-contrast microscopy or fluorescence microscopy.
RESULTS: The EC50 of glucose for the three cancer cell lines ranged from 0.54 to 4.88 mM. The EC50 of glucose for Hs27 normal fibroblasts was 0.35 mM, which was not significantly lower than in HCT116 cells (p=0.2225). The EC50 for glutamine ranged from 0.15 to 0.54 mM for the cancer-cell lines and 0.24 mM for normal fibroblasts, which did not distinguish normal from cancer cells. For comparison the EC50 of cancer cells for methionine ranged from 3.8 μM to 21.4 μM while for normal fibroblasts the EC50 for methionine was 2.3 μM, which was significantly lower than in all the cancer cell lines (p<0.0167). In co-culture of cancer and normal fibroblasts, glucose-free or glutamine-free medium resulted in loss of cell viability by day 7 for both the cancer and normal cells. In contrast, in methionine-free medium, the normal fibroblasts were alive and healthy at day 7.
CONCLUSION: The Warburg effect of glucose and glutamine addiction is not cancer specific in comparison to methionine addiction (Hoffman effect), which is cancer specific, suggesting the Warburg effect is not a cancer paradigm.

Keywords:  Glucose; Hoffman effect; Warburg effect; cancer cells; cancer-specific; co-culture; glutamine; methionine; normal fibroblasts; paradigm; requirement; vulnerability

DOI:  https://doi.org/10.21873/anticanres.18080
Blood. 2026 Mar 26. 147(13): 1504

Ronceray L, Huibers MHW, Reutter K, et al. High-grade/large B-cell lymphoma-11q has a very good prognosis in children and young people without a predisposition. Blood. 2026;147(2):209-214.

DOI: https://doi.org/10.1182/blood.2026033346
Curr Oncol. 2026 Mar 13. pii: 164. [Epub ahead of print]33(3):

Maintenance Strategies in High-Risk Myeloma: A Multicenter Comparison of Bortezomib-Lenalidomide Versus Lenalidomide Alone: A USMIRC Multicenter Analysis.

Sruthi P Ramanan, Oyepeju F Abioye, Shebli Atrash, Jianzheng Wu, Dinesh Pal Mudaranthakam, Anita Mazloom, Omar Alkharabsheh, Mansi R Shah, Zahra Mahmoudjafari, Jordan Snyder, Muhammad Umair Mushtaq, Forat Lutfi, Jeries Kort, Al-Ola Abdallah, Prerna Mewawalla.

  Background: Lenalidomide maintenance after autologous stem cell transplantation (ASCT) improves progression-free survival (PFS) and overall survival (OS) in multiple myeloma; however, these benefits are attenuated in high-risk multiple myeloma (HRMM). No standard post-transplant maintenance strategy is established for HRMM, and some centers employ doublet maintenance with bortezomib plus lenalidomide (VR). We evaluated outcomes with VR versus lenalidomide alone (R) in HRMM. Methods: We conducted a multicenter retrospective study through the US Myeloma Innovations Research Collaborative (USMIRC), including adults with HRMM who received R or VR maintenance following ASCT between January 2009 and January 2024. HRMM was defined by del(17p), t(4;14), t(14;16), or t(14;20), with or without 1q gain. PFS and OS were estimated using Kaplan-Meier methods. Median follow-up was 91 months. Baseline characteristics, induction regimens, and post-transplant response depth were well balanced between the groups. Median PFS was 51 months (95% CI, 20-NR) with VR and 36 months (95% CI, 31-56) with R (p > 0.05). Median OS was 103 months (95% CI, 90-NR) and 110 months (95% CI, 94-NR), respectively (p > 0.05). VR was associated with numerically longer PFS, although the difference was not statistically significant. No treatment-related mortality occurred within 100 days post-ASCT. Conclusions: In this multicenter real-world analysis of HRMM, VR maintenance did not result in statistically significant improvements in PFS or OS compared with lenalidomide alone. These findings underscore the need for prospective, risk-adapted trials incorporating novel maintenance strategies, including CD38- and BCMA-directed therapies, in high-risk disease.

Keywords:  bortezomib; doublet maintenance; high-risk multiple myeloma; lenalidomide; post-ASCT maintenance

DOI:  https://doi.org/10.3390/curroncol33030164
Blood. 2026 Mar 27. pii: blood.2025031102. [Epub ahead of print]

IGH::FENDRR and specific KRAS mutations define a novel B-ALL molecular subtype with poor chemotherapy response.

Sonja Bendig, Alina M Hartmann, Wiebke Wessels, Thomas Beder, Rathana Kim, Marie Passet, Qingsong Gao, Nadine Wolgast, Johanna M Horns, Leonardo Alves Santos, Katharina Iben, Fabio D Steffen, Loredana Cantoni, Britta Kehden, Guranda Chitadze, Axel Künstner, Hauke Busch, Beat Bornhauser, Jean-Pierre Bourquin, Thibaut Tl Leguay, Nicolas Boissel, Nicola Gökbuget, Ilaria Iacobucci, Charles G Mullighan, Emmanuelle Clappier, Claudia D Baldus, Monika Brüggemann, Lorenz Bastian.

Large scale sequencing efforts have defined up to 27 diagnostic entities in B-ALL, leaving few samples without subtype assignment. Extended genomic and transcriptomic profiling in routine diagnostics broadens the sample collection and holds the potential to identify novel B-ALL subtypes. By analyzing an aggregated set of 4,857 B-ALL patients from three cohorts, we identified a novel group of twenty cases (age 18-66 years, median: 34 years) characterized by a previously undescribed IGH::FENDRR rearrangement exclusive to this subtype (n=17/20), KRAS p.A146T/V/P mutations (n=17/20 vs. n=86/4,857; p<0.001) and distinct DNA-methylation/gene expression profiles, including overexpression of the lncRNA FENDRR and the transcription factor FOXF1 ('FOXF1/FENDRR') as well as JAK/STAT and RAS signaling signatures. A gene expression machine learning classifier identified FOXF1/FENDRR cases in two independent cohorts with high accuracy. Patients treated according to GMALL/GRAALL protocols showed very poor chemotherapy response with n=8/13 having induction failure or MRD ≥10-3 and n=8/12 remaining MRD positive after 1st consolidation / salvage. MRD-stratified intensification including blinatumomab (n=10) and/or allogenic stem cell transplantation (n=12) resulted in ongoing molecular remission in 13/16 cases. FOXF1/FENDRR patients represent a novel B-ALL subtype which might benefit from early immunotherapeutic treatment or targeted interventions.

DOI: https://doi.org/10.1182/blood.2025031102
Cancers (Basel). 2026 Mar 18. pii: 982. [Epub ahead of print]18(6):

Targeting Mitochondrial Vulnerabilities in Chronic Myeloid Leukemia: From Pathobiology to Novel Therapeutic Opportunities.

Francesco Caprino, Ilenia Valentino, Antonella Bruzzese, Ludovica Ganino, Maria Mesuraca, Rita Citraro, Massimo Gentile, Maria Eugenia Gallo Cantafio, Nicola Amodio.

  Background: Mitochondria are multifunctional organelles that play a central role in maintaining cellular homeostasis by regulating energy metabolism, reactive oxygen species (ROS) generation, ion homeostasis, and apoptotic signaling. Dynamic processes such as mitochondrial fission, fusion, and intracellular trafficking enable cells to adapt to metabolic and environmental stress. Growing evidence indicates that dysregulation of these processes is a hallmark of cancer, contributing to metabolic reprogramming, redox imbalance, evasion of apoptosis, and disease progression. This narrative review aims to discuss the role of mitochondrial alterations in the pathophysiology of chronic myeloid leukemia (CML) and their potential therapeutic implications. Methods: Original research articles published between 2010 and 2025 were considered in this narrative review. The selected studies were critically discussed and categorized into three principal thematic domains: mitochondrial regulation of redox homeostasis, metabolic rewiring, and control of cell death pathways. Evidence was synthesized to elucidate the contribution of mitochondrial dysfunction to CML initiation, progression, and therapeutic resistance. Results: The reviewed studies highlight how mitochondrial abnormalities play a pivotal role in BCR-ABL1-driven leukemogenesis. Alterations in mitochondrial metabolism and ROS signaling support sustained proliferative signaling, promote genomic instability, and facilitate resistance to apoptosis. In addition, mitochondrial adaptations contribute to resistance to tyrosine kinase inhibitors (TKIs) and are essential for the persistence and survival of leukemic stem cells. Conclusions: Mitochondria emerge as central regulators of CML pathobiology. Therapeutic strategies targeting mitochondrial metabolism, redox homeostasis, and apoptotic signaling pathways represent promising approaches to overcoming TKI resistance and may improve clinical outcomes for patients with CML.

Keywords:  Chronic Myeloid Leukemia; metabolic reprogramming; mitochondrial dysfunction; oxidative stress

DOI:  https://doi.org/10.3390/cancers18060982
Blood. 2026 Mar 23. pii: blood.2025030859. [Epub ahead of print]

From Breakthroughs to Blueprints: Evolving Evidence and Future Directions in Relapsed and Refractory Large B-Cell Lymphoma.

Manali Kamdar, Nancy L Bartlett.

The therapeutic landscape for relapsed or refractory large B-cell lymphoma (R/R LBCL) has undergone rapid and profound change, driven by cellular therapies, bispecific antibodies, and next-generation antibody-drug conjugates (ADCs). These advances have redefined historical standards while exposing persistent gaps in trial design, biological insight, and therapeutic sequencing. Recent randomized studies show that ADC- and bispecific-anchored regimens can outperform legacy chemotherapy comparators, yet interpretation is hindered by geographic heterogeneity, selective enrollment, and a proliferation of trials lacking contemporary control arms.Next-generation approaches including bispecific-ADC combinations, dual-target CAR-T constructs, and strategies explicitly designed to circumvent antigen escape are poised to challenge long-standing therapeutic hierarchies and may broaden curative potential to patients who are ineligible for, or relapse after, CAR-T. The field now stands at an inflection point where therapeutic innovation is advancing faster than the evidence infrastructure required to guide practice. Delivering durable, equitable benefit will require control arms aligned with current CAR-T standards, harmonized eligibility criteria, prospective molecular profiling, and adaptive trial platforms capable of evolving with the standard of care.As ADCs and bispecifics move earlier in treatment and diffuse into community practice, the central challenge is no longer the development of active therapies alone, but the creation of biologically rational, accessible, and interpretable pathways that make chemotherapy-free cure a realistic and universal goal for patients with R/R LBCL.

DOI: https://doi.org/10.1182/blood.2025030859
Haematologica. 2026 Mar 26.

Disrupting adaptive proteostasis to overcome proteasome inhibitor resistance.

Annamaria Brioli.

Not available.

DOI: https://doi.org/10.3324/haematol.2026.300486
Ann Pathol. 2026 Mar 25. pii: S0242-6498(26)00028-3. [Epub ahead of print]

[Follicular and follicle center-cell lymphomas: A family between kinship and diversity].

Florian Pesce, Marie Donzel, Alexandra Traverse-Glehen, Camille Laurent, Luc Xerri.

  Follicular lymphoma (FL) is the second most common B-cell lymphoma in adults. It is classically characterized by a B-cell proliferation of follicular architecture consisting of a mixture of centrocytes and centroblasts. FL cells have a germinal center phenotype and carry the t(14;18)/IGH::BCL2 translocation, the hallmark of FL in 90% of cases. Nevertheless, FL may display particular morphological and molecular characteristics recognized as variants or distinct entities in both the WHO-HAEM5 and International Consensus Classification (ICC). One of the major changes in the WHO-HAEM5 is that the grading of low-grade FL is no more mandatory due to the merging of grades 1, 2 and 3A into a "classic FL" (cFL) subtype, whereas FL with unusual cytological features (uFL) should be identified as a specific variant. uFL is characterised by a proliferation of large centrocytes or small centroblasts/blastoid cells, which do not fit the cytological criteria for grade 3A or 3B. FL grade 3B (which remains unchanged in the ICC) is renamed "follicular large B-cell lymphoma" in the WHO-HAEM5. Duodenal-type FL still remains as a specific subtype characterized by an indolent disease localised to the digestive tract, and harboring a BCL2 rearrangement (BCL2-R). Both current classifications recognize some categories of BCL2-R negative FL including the "predominantly diffuse FL" (WHO-HAEM5) (overlapping with the "BCL2-R negative/CD23 positive follicle center lymphoma" according to the ICC) often presenting in the inguinal region with an indolent course; the paediatric-type FL and the testicular FL affecting children or young adults. The recently described "follicle center lymphoma of the lower female genital tract" shows some similarities with primary cutaneous follicle center lymphoma.

Keywords:  Classification; Diagnosis; Diagnostic; Follicular lymphoma; Lymphome folliculaire

DOI:  https://doi.org/10.1016/j.annpat.2026.02.007
Cureus. 2026 Feb;18(2): e103856

From Molecular Silence to Lymphoid Blast Phase: Diagnostic and Therapeutic Challenges in a Young Female Patient With Chronic Myeloid Leukemia.

Zainab H Alqallaf, Sara Atwa.

  Chronic myeloid leukemia (CML) is a triphasic myeloproliferative neoplasm characterized by the breakpoint cluster region-Abelson BCR::ABL1 fusion gene, typically detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We present a case of a 20-year-old female patient who presented with non-specific constitutional symptoms and was diagnosed with CML based upon detection of the Philadelphia (Ph) chromosome by fluorescence in situ hybridization (FISH), while repeated molecular testing remained negative. Notably, during treatment with tyrosine kinase inhibitors (TKIs), she became intolerant to first- and second-generation TKIs, including the branded and generic imatinib, nilotinib, and dasatinib, followed by progression into lymphoid blast phase. This case highlights the diagnostic challenges and therapeutic complexity of managing CML in the setting of multi-TKI intolerance. Importantly, it underscores the persistent molecular silence despite repeated RT-qPCR testing and the successful introduction of asciminib as a novel therapeutic alternative.

Keywords:  asciminib; b-lymphoblastic phase; chronic myeloid leukemia (cml); molecular silence; tki intolerance; tyrosine kinase inhibitor (tki)

DOI:  https://doi.org/10.7759/cureus.103856
Blood Adv. 2026 Mar 24. 10(6): 2104-2105

A new era for heavy menstrual bleeding.

Veronica H Flood.

DOI: https://doi.org/10.1182/bloodadvances.2025019155
J Oncol Pharm Pract. 2026 Mar 17. 10781552261430675

Primary central nervous system lymphoma: Evolving treatment strategies to achieve improved long-term disease control.

Moza Hamoud, Victor M Samperio, Ion Codreanu, Constantin A Dasanu.

  ObjectiveDespite high initial response rates to chemotherapy, long-term disease control in primary central nervous system lymphoma (PCNSL) remains challenging, with high relapse rates and no universally accepted standard for induction or consolidation therapy. This review discusses current strategies, new advancements and clinical trial results for PCNSL.Data SourcesAn extensive Medline, Embase and Cochrane search of peer-reviewed sources reporting on pharmacotherapy of PCNSL was performed (1/1/2000-12/31/2025). Analysis of original research including clinical trial results, retrospective series and other reports were included in this review.Data SummaryThis review summarizes the current understanding of PCNSL, including epidemiology, clinical presentation, diagnostic evaluation, and response assessment, with a focus on pharmacologic management. We discuss modern induction strategies centered on high-dose methotrexate (HD-MTX) and rituximab, consolidation approaches including reduced-dose whole-brain radiotherapy (WBRT), autologous stem cell transplantation (ASCT), and maintenance strategies, as well as emerging therapies for relapsed or refractory disease. A case of a 76-year-old patient achieving sustained remission exceeding seven years following rituximab plus HD-MTX induction and consolidative therapy is presented to illustrate the potential for durable disease control and even cure. These data underscore the importance of individualized treatment selection based on patient age, fitness level and response to induction and highlight that lasting remission is achievable in select patients with optimized, multimodal therapy.ConclusionsDespite its rarity, PCNSL remains a therapeutically challenging malignancy. HD-MTX-based chemotherapy remains the cornerstone of first-line treatment, and the addition of rituximab has been associated with more sustained responses. Although relapses are not uncommon, long-term remission is achievable. Clinical trials of newer agents, alone or added to a backbone of traditional chemotherapy, are warranted in the 1st and subsequent lines of therapy. Continued prospective research and international collaboration are essential to integrate precision oncology to the bedside of patients with PCNSL.

Keywords:  Primary central nervous system lymphoma; chemotherapy; high-dose methotrexate; reduced-dose radiation therapy; rituximab; targeted agents

DOI:  https://doi.org/10.1177/10781552261430675
Cancer. 2026 Apr 01. 132(7): e70360

Combination of mitoxantrone hydrochloride liposome with cyclophosphamide, vincristine, and prednisone for patients with treatment-naive peripheral T-cell lymphoma: A multicenter, open-label, single-arm, phase 1b trial.

Yan Gao, Ming Jiang, Xuanye Zhang, Lihong Liu, Liling Zhang, Yufu Li, Xin Wang, Xiaojing Yan, Hui Zhou, Huiqiang Huang.

   BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphomas. Most subtypes are generally associated with a poor prognosis when treated with standard chemotherapy.
METHODS: This study enrolled patients with untreated PTCL who received mitoxantrone hydrochloride liposome (Lipo-MIT) plus cyclophosphamide, vincristine, and prednisone (CMOP) every 4 weeks for six cycles. The study consisted of a 3 + 3 dose-escalation phase (Lipo-MIT at 12, 15, 18, and 21 mg/m2) and a specific dose-expansion phase (Lipo-MIT at the recommended phase 2 dose [RP2D]).
RESULTS: Between December 21, 2020, and November 17, 2022, 38 patients were enrolled. No dose-limiting toxicities were reported, and the RP2D was established at 18 mg/m2. Grade ≥3 treatment-related adverse events occurred in 33 (86.8%) patients, with the most common being neutrophil count decrease (76.3%) and white-cell count decrease (73.7%). No treatment-related deaths occurred. Among the 35 response-evaluable patients, the independent review committee-assessed complete response rate (CRR) was 54.3% (95% CI, 36.6%-71.2%), and the overall response rate (ORR) was 88.6% (95% CI, 73.3%-96.8%). For the 17 patients treated at RP2D, the CRR, ORR, median duration of CR, and median duration of response were 64.7% (95% CI, 38.3%-85.8%), 94.1% (95% CI, 71.3%-99.9%), 28.0 (95% CI, 9.8-46.3) months, and 28.0 (95% CI, 4.0-52.1) months, respectively. At a median follow-up of 23.8 months, the median progression-free survival was 20.8 (95% CI, 6.1-35.5) months, and the median overall survival was not reached. Lipo-MIT exhibited a favorable pharmacokinetics (PK) profile.
CONCLUSION: The CMOP regimen demonstrates a favorable PK profile, a manageable safety profile, and encouraging preliminary antitumor activity.

Keywords:  CMOP; mitoxantrone hydrochloride liposome; peripheral T‐cell lymphoma; phase 1b; treatment‐naive patients

DOI:  https://doi.org/10.1002/cncr.70360
N Engl J Med. 2026 Mar 26. 394(12): 1238-1240

Treatment-free Remission in Chronic Myeloid Leukemia in Low- and Middle-Income Countries.

Alicia Annamalay, Inés García González, Colin Forsyth, Isaac Jenkins, Mercedes Arteaga, Nicholas A Othieno-Abinya, Chirag Desai, Flora Duarte, Vadavattath P Gangadharan, Sadashivudu Gundeti, Hemant Malhotra, Pankaj Malhotra, Karen Meliksetyan, Rafael Mojica, José Zarza, Juan Miguel Sabonge, Anyelis Lucia Santana, Amha Gebremedhin, Rafael Orellana Martínez, Maritza Martínez Miranda, Marta Griselda Lima Valencia, Pat Garcia-Gonzalez, Jerald Radich.

DOI: https://doi.org/10.1056/NEJMc2518028
Blood Adv. 2026 Mar 27. pii: bloodadvances.2025019223. [Epub ahead of print]

Management of relapsed/ refractory AL amyloidosis.

Jessica Ling, M Hasib Sidiqi, Morie A Gertz.

Frontline therapy for systemic light chain (AL) amyloidosis has evolved significantly with the approval of daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCD), which has significantly improved rates of both hematologic and organ responses. Despite these advances, many patients eventually relapse, and there remains no established standard salvage regimen or optimal timing. In this review, we examine optimal timing of salvage regimens and currently available therapeutic options following daratumumab failure, including next generation proteosome inhibitors or immunomodulatory drugs, autologous stem cell transplant, BCL-2 inhibitors and emerging immunotherapeutic agents such as chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies).

DOI: https://doi.org/10.1182/bloodadvances.2025019223
Blood Neoplasia. 2026 May;3(2): 100194

Survival after intensive therapy or clofarabine in fit older adults with acute myeloid leukemia: E2906 phase 3 trial.

James M Foran, Zhuoxin Sun, Selina M Luger, David F Claxton, Hillard M Lazarus, Daniel A Arber, Jacob M Rowe, Elisabeth Paietta, Janis Racevskis, Fran Garrett-Bakelman, Yanming Zhang, Jessica K Altman, Aref Al-Kali, Hong Zheng, Keith W Pratz, E Randolph Broun, Bayard L Powell, Kristen Marie O'Dwyer, John E Godwin, Yishai Ofran, Mark R Litzow, Martin S Tallman.

Clofarabine is a second-generation purine nucleoside analog with encouraging reported 30-day induction mortality (IM) and complete remission (CR) or CRi (incomplete platelet recovery) rates, and represents a lower-intensity therapy for older adults with acute myeloid leukemia (AML). We evaluated long-term outcomes in a prospective phase 3 study using a noninferiority design. Patients aged ≥60 years with newly diagnosed AML and normal renal and cardiac function were randomized to standard intensive daunorubicin and cytarabine or single-agent clofarabine. The primary objective was overall survival (OS) using a weighted analysis. We incorporated prospective central testing for measurable residual disease (MRD; ≥0.1%) at remission using multiparameter flow cytometry. Among 727 patients (standard, n = 363; clofarabine, n = 364), there was no difference in CR/CRi (50%) or IM (8.5%) rates. The median follow-up was 58.6 months. In the primary analysis, OS was inferior with clofarabine (median, 10.4 vs 12.4 months [standard]; P = .04), although not in patients aged ≥70 years, with secondary AML, or unfavorable cytogenetics. Allogeneic transplantation was strongly associated with OS on multivariate analysis (HR, 0.53; P < .0001). MRD-negative remission was achieved in 41% of patients and strongly associated with 5-year OS irrespective of treatment (MRD-positive, 48.8% vs 12.2%; P = .003). In contrast, MRD-positive patients assigned to clofarabine (vs high-dose cytarabine) consolidation had significantly inferior OS. Clofarabine is inferior to standard intensive therapy despite similar remission rates. Achieving MRD-negative remission is associated with high, sustained rates of OS regardless of therapy. Increasing MRD negativity and improving outcomes among MRD-positive patients remain pressing, ongoing challenges. This trial was registered at www.clinicaltrials.gov as NCT02085408.

DOI: https://doi.org/10.1016/j.bneo.2026.100194
Cancer. 2026 Apr 01. 132(7): e70341

Final clinical data of a phase 1 dose-escalation study of WVT078, a BCMA×CD3 bispecific antibody, alone and in combination with γ-secretase inhibitor WHG626 in patients with relapsed and/or refractory multiple myeloma.

Fredrik Schjesvold, Andrew Spencer, Yael C Cohen, Enrique M Ocio, Jordi Lopez-Pardo, Anna Maria Cafro, Natalie S Callander, Jonathan L Kaufman, Meera Mohan, Martin Wermke, Noriko Doki, Rebecca Kan, Pedro Milanez-Almeida, Andrew Stein, Gina Trabucco, Stan Ye, Karolina Kulec, Romain Sechaud, Souvik Banerjee, Huiqin Zhong, Clinton Lai, Philipp J Rauch, Marc S Raab.

   BACKGROUND: This first-in-human phase 1 study evaluated the B-cell maturation antigen (BCMA)×CD3 bispecific antibody WVT078 alone and in combination with the γ-secretase inhibitor WHG626 in patients with relapsed/refractory multiple myeloma (r/r MM).
METHOD: The primary objectives were to assess safety, tolerability, and to determine the recommended doses (RDs) and regimens for expansion for WVT078 and WHG626. Secondary objectives included the assessment of preliminary antitumor activity and characterization of pharmacokinetics and immunogenicity.
RESULT: Overall, 56 patients were treated in the dose-escalation part of the study, seven of whom experienced dose-limiting toxicities. Across all dose levels, cytokine release syndrome was the most common treatment-related adverse event. WVT078 monotherapy showed an overall response rate (ORR) of 27.3% and a complete response rate (CRR) of 12.1%. WVT078 combined with WHG626 demonstrated an ORR of 47.8% and a CRR of 21.7%. RDs were not declared, and dose expansion was not initiated.
CONCLUSION: WVT078 administered with and without WHG626 showed a manageable safety profile. Preliminary activity was observed in patients with r/r MM. The addition of WHG626 numerically improved response over WVT078 monotherapy. Findings from this study support further evaluation of WHG626 as a combination partner of BCMA-targeting agents for r/r MM treatment.

Keywords:  BCMA×CD3 bispecific antibody; WHG626; WVT078; combination therapy; dose‐escalation study; relapsed and/or refractory multiple myeloma; γ‐secretase inhibitor

DOI:  https://doi.org/10.1002/cncr.70341
Endocr Oncol. 2026 Jan;6(1): e250057

Vitamin D receptor expression in germinal centre type diffuse large B-cell lymphoma cells is associated with vitamin D insensitivity.

Elizabeth J Soilleux, Amanda Anderson, Emma Roberts, Linden Lyne, Kah Keng Wong, Hayley Spearman, Stefano Casola, Alison H Banham, Duncan M Gascoyne.

   Objective: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of non-Hodgkin lymphomas (NHLs) often sub-classified into major germinal centre (GC) and activated B-cell (ABC) cell-of-origin types. We have previously shown vitamin D receptor (VDR) expression in plasmablastic ABC-DLBCL cells and demonstrated inhibition of their growth by exogenous vitamin D (VitD3); however, the vitamin D biology of GC-DLBCL cells remained unclear.
Design/methods: Study of VDR and related molecule expression and vitamin D response across a panel of DLBCL and myeloma cell lines by western blot, qPCR, flow cytometry and cell counting techniques. Analysis of gene expression and ChIP-seq in published cell line and/or primary DLBCL datasets.
Results: We show that some BCL6hi GC-DLBCL cell lines express low levels of VDR, but appear resistant to VitD3, and associate VDR positivity in both GC- and ABC-DLBCL cell lines with the poor prognosis plasmacytic/activation marker CD38. ChIP-seq data suggest that VDR may be a direct BCL6 target. Functionally, VitD3 and the EB-1089 analogue can reduce growth, inhibit MYC expression and increase CD38 expression by 50-400% on ABC-DLBCL and myeloma but not GC-DLBCL cells. CD38 is also activated by VitD3 treatment of human peripheral B cell lines, where VDR can bind to the CD38 locus, suggesting direct regulation.
Conclusions: Combined VDR and cell-of-origin assessment may contribute to a greater understanding of vitamin D's role in mature B-cell lymphoma and its interplay with BCL6 and MYC.

Keywords:  BCL6; CD38; DLBCL; EB-1089; MYC; VitD3; daratumumab; growth arrest; myeloma; non-Hodgkin’s lymphoma; vitamin D receptor (VDR)

DOI:  https://doi.org/10.1530/EO-25-0057
Int J Surg Pathol. 2026 Mar 23. 10668969261422270

Masquerading as an Interstitial Lung Disease: Intravascular Large B-Cell Lymphoma With Prominent Neo-Angiogenesis.

Andreas Lancelot, Anne-Marie Delsupehe, Vibeke K J Vergote, Jolien De Bie, Lucienne Michaux, Thomas Tousseyn, Birgit Weynand, Arno Vanstapel.

  Intravascular large B-cell lymphoma forms a rare entity that may mimic disease symptoms according to the affected sites. It is characterized by the presence of large atypical lymphoid B cells restricted to intravascular spaces, especially capillaries. We present a 65-year-old man who presented with a concurrent intravascular large B-cell lymphoma and Waldenström macroglobulinemia with prominent pulmonary symptoms masquerading as a hypersensitivity pneumonitis. A subsequent surgical lung biopsy illustrated peribronchial and interstitial nodular aggregates which consisted of numerous capillary structures filled with neoplastic B lymphocytes. This report hints toward potential induction of prominent neo-angiogenesis by intravascular large B-cell lymphoma, with development of intrapulmonary nodular aggregates mimicking interstitial lung disease.

Keywords:  IVLBCL; Waldenström macroglobulinemia; hypersensitivity pneumonitis; intravascular large B-cell lymphoma; neo-angiogenesis; pulmonary disease

DOI:  https://doi.org/10.1177/10668969261422270
Ther Adv Hematol. 2026 ;17 20406207261424845

Assessment of flonoltinib maleate versus ruxolitinib phosphate in intermediate- to high-risk myelofibrosis (FMF-02): study protocol for a multicenter, randomized, open-label phase IIB trial.

Linyu Yang, Ke Tan, Rui Liang, Wei Zhang, Yiqun Wang, Lijuan Chen.

   Background: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, splenomegaly, debilitating constitutional symptoms, and cytopenias. Despite the benefits of ruxolitinib in controlling symptoms and spleen volume, challenges such as myelosuppression and limited impact on underlying fibrosis persist, particularly in cytopenic patients. Flonoltinib maleate (FM), a novel JAK2/FLT3/CDK6 inhibitor, shows preliminary potential in improving hematologic parameters and reducing fibrosis.
Objectives: To evaluate the efficacy of low-/high-dose FM compared with RUX (primary objective), along with safety and the pharmacokinetic profile of FM (secondary objectives), in patients with intermediate- to high-risk MF (Trial registration: NCT06457425).
Design: FMF-02 is a multicenter, randomized, open-label, active-controlled, phase IIb clinical trial.
Methods: Approximately 75 adults with primary or secondary MF will be randomized in a 1:1:1 ratio to receive low-dose FM (50 mg once daily), high-dose FM (100 mg once daily), or RUX (5, 15, or 20 mg twice daily, based on platelet count), with randomization stratified by the Dynamic International Prognostic Scoring System risk category. The primary endpoint is the proportion of patients achieving ⩾35% spleen volume reduction (SVR35) at week 24, as assessed by a blinded Independent Review Committee. Key secondary endpoints include the proportion with ⩾50% reduction in Total Symptom Score (TSS50), changes in myelofibrosis grade, objective remission rate [International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria], and safety. Subjects in the RUX group who complete the 24-week treatment or experience disease progression due to splenomegaly will crossover to receive FM. All subjects will continue long-term therapy until meeting discontinuation criteria, followed by survival follow-up.
Results: The study commenced in June 2024 and is currently ongoing. The results will provide comparative data on the efficacy and safety profiles of FM versus RUX, including analyses of spleen response, symptom burden, hematologic parameters, and bone marrow fibrosis.
Conclusion: The FMF-02 trial is the first randomized phase IIb study directly comparing the novel inhibitor FM against RUX. Its findings are expected to generate pivotal evidence regarding whether FM offers superior or differentiated clinical benefits, thereby informing its potential as a frontline therapy for intermediate- to high-risk MF and guiding the design of future phase III studies.

Keywords:  JAK2/FLT3/CDK6 inhibitor; efficacy and safety; flonoltinib maleate; myelofibrosis; phase IIb protocol; randomized controlled trial; ruxolitinib phosphate

DOI:  https://doi.org/10.1177/20406207261424845