bims-hemali 2026-05-03 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2026–05–03
fifteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Therapeutic Targets for Overcoming BCR::ABL1 Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia.
Immune clues to infection risk in myeloma.
Elranatamab: Mechanism of Action, Clinical, and Translational Science.
The lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat in myelofibrosis: results from a phase 1/2 study.
Checkpoint blockade in HL: is transplant still needed?
Cladribine With Low-Dose Cytarabine and Venetoclax Alternating With Azacitidine and Venetoclax for Newly Diagnosed Acute Myeloid Leukemia.
Asciminib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Case Series and Review of Emerging Evidence.
How I Treat Plasma Cell Leukemia.
Sonrotoclax: First Approval.
Inferior Outcomes of p230-CML with Imatinib: a Report of 2 Cases of p210/p230 Co-Expressed CML Showing Rapid Progression To Leukaemia Cutis along with the Systematic Review.
Zanubrutinib in Hairy Cell Leukemia Variant: Clinical Report and Overview of BTK Inhibition in Variant Disease.
Impact of the diagnosis-to-treatment interval on the survival of patients with CD5-positive diffuse large B-cell lymphoma.
Role of Flow Cytometric Enumeration of Circulating hMICL (CD371) Positive Leukemic Stem Cells in Diagnosis and Prognostication of BCR::ABL1-Negative Myeloproliferative Neoplasms.
French protocol for the diagnosis and management of autoimmune hemolytic anemia in adults.
Multicenter Real-World Analysis of Glofitamab in Relapsed/Refractory Primary CNS Lymphoma: Clinical Activity, CNS Penetration, and ctDNA Dynamics.

Oncol Res. 2026 ;34(5): 7

Therapeutic Targets for Overcoming BCR::ABL1 Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia.

Masanobu Tsubaki, Taira Matsuo, Rie Komori.

  Chronic myeloid leukemia (CML) is a hematopoietic malignancy originating from hematopoietic stem cells. It is characterized by the Philadelphia chromosome, which arises from a reciprocal translocation between chromosomes 9 and 22. The breakpoint cluster region::Abelson murine leukemia 1 (BCR::ABL1) fusion protein produced from this chromosome is the main factor responsible for disease onset. Tyrosine kinase inhibitors (TKIs) have led to significant advances in CML treatment and contributed to improved patient survival rates. Nonetheless, a substantial number of patients develop resistance to TKIs, which remains a major challenge in CML therapy. Currently, two mechanisms are considered responsible for TKIs resistance in CML: BCR::ABL1-dependent resistance, involving mutations or overexpression of BCR::ABL1, and BCR::ABL1-independent resistance, which does not depend on BCR::ABL1. This review discusses the recent findings on the resistance mechanisms mediated by BCR::ABL1 mutations. It also focuses on bypass pathways, the B-cell/CLL lymphoma 2 family, tumor suppressor genes, microRNAs, and molecular chaperones as independent resistance mechanisms. Furthermore, the potential for combination therapies targeting these resistance mechanisms is discussed, anticipating further advances in research aimed at overcoming TKI resistance in CML.

Keywords:  Chronic myeloid leukemia; breakpoint cluster region::Abelson murine leukemia 1; resistance; tyrosine kinase inhibitor

DOI:  https://doi.org/10.32604/or.2025.075217
Blood. 2026 Apr 30. 147(18): 2024-2025

Immune clues to infection risk in myeloma.

Louise Ainley, Kwee Yong.

DOI: https://doi.org/10.1182/blood.2026033248
Clin Transl Sci. 2026 May;19(5): e70554

Elranatamab: Mechanism of Action, Clinical, and Translational Science.

Mohamed Elmeliegy, Andrea Viqueira, Erik Vandendries, Pooneh Soltantabar, Hoi-Kei Lon, Kamrine Poels, Blerta Shtylla, Donald Irby, Kristin Bompiani-Myers, Thomas O'Brien, Jennifer Hibma.

  Elranatamab (ELREXFIO) is a humanized bispecific antibody approved for patients with relapsed/refractory multiple myeloma (RRMM). Elranatamab engages CD3 on T cells and B-cell maturation antigen (BCMA) on myeloma cells to induce T cell-mediated myeloma cell cytolysis. The recommended subcutaneous elranatamab dosing consists of fixed step-up doses of 12 mg on day 1 and 32 mg on day 4 to mitigate the incidence and severity of cytokine release syndrome (CRS), followed by the full fixed dose of 76 mg once weekly (QW) from weeks 2 to 24. In responders, 76 mg QW is reduced to every 2 weeks (Q2W) after ≥ 6 QW cycles and to every 4 weeks after ≥ 6 Q2W cycles. The full dose (76 mg QW) results in a higher probability of achieving an objective response versus lower doses without worsening the safety profile. This regimen was based on the collective safety, efficacy, pharmacokinetic, and pharmacodynamic data from MagnetisMM-1, -2, -3, and -9. In the pivotal MagnetisMM-3 study, in patients with BCMA-naive RRMM, elranatamab resulted in a 61.0% overall response rate; 37.4% achieved complete response or stringent complete response. Median duration of response was not yet reached; the probability of maintaining response at 30 months was 61.0%. Median progression-free and overall survival were 17.2 and 24.6 months, respectively. In MagnetisMM-3 patients, common adverse events (≥ 40%; any grade/grade 3/4) included infections (71.7%/38.5%), CRS (58.8%/0.5%), anemia (53.5%/42.2%), neutropenia (46.0%/44.4%), and diarrhea (42.8%/3.2%). Elranatamab demonstrated deep and durable responses, a manageable safety profile, and low-grade CRS with predictable timing. Elranatamab is being further evaluated as monotherapy or combination therapy in earlier treatment lines.

Keywords:  B‐cell maturation antigen; bispecific antibody; elranatamab; multiple myeloma

DOI:  https://doi.org/10.1111/cts.70554
Blood Adv. 2026 Apr 29. pii: bloodadvances.2025018141. [Epub ahead of print]

The lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat in myelofibrosis: results from a phase 1/2 study.

Harinder Gill, Abdulraheem Yacoub, Aaron T Gerds, Jake Shortt, James M Rossetti, Adam J Mead, Joachim R Göthert, Steffen Koschmieder, Joanne Ewing, Anna B Halpern, Francesca Palandri, Francesco Passamonti, Ruben A Mesa, Monia Marchetti, Claire N Harrison, Alessandro M Vannucchi, Justin M Watts, John C Wood, David M Ross, Jennifer Peppe, Georges Natsoulis, Hugh Young Rienhoff.

Novel therapies for myelofibrosis (MF) are needed, particularly after JAK inhibitor failure. This open-label, phase 1/2 study evaluated bomedemstat, an irreversible inhibitor of lysine-specific demethylase 1 (LSD1), in participants with MF refractory or resistant to, inadequately controlled by, or intolerant of approved therapies. Eighty-nine participants initially received bomedemstat 0.25, 0.5, or 0.6 mg/kg orally once per day titrated to achieve a target platelet count of ≥50 to ≤75 ´ 109/L. Primary end points were safety and change in spleen volume. Hematologic response and change in symptom burden, bone marrow fibrosis score, and variant allele frequency (VAF) were exploratory. Eighty-seven participants (97%) experienced ≥1 any-cause adverse event (AE), most commonly thrombocytopenia (48%) and dysgeusia (36%); 62 participants (69%) experienced ≥1 grade 3-5 AE. Three participants (3%) experienced AEs that led to death; none were related to treatment. Of 35 participants with spleen volume data at week 24, 23 (66%) had a reduction in spleen volume; 9 (26%) had a reduction of ≥20%. Mean platelet and white blood cell counts normalized over 24 weeks; hemoglobin levels remained stable. Participants reported improvement in most symptoms, including fatigue. Of 35 participants with baseline and week 24 data, 8 (23%) had improved bone marrow fibrosis by ≥1 grade per central review, and 21 (60%) were stable. Of 36 participants with CALR, JAK2, or MPL mutations and data at week 24, 56% had a reduction in VAF. Bomedemstat has manageable safety and clinical activity in participants with MF in need of an alternative therapy. This trial was registered at www.cinicaltrials.gov as #NCT03136185.

DOI: https://doi.org/10.1182/bloodadvances.2025018141
Blood. 2026 Apr 30. 147(18): 2021-2022

Checkpoint blockade in HL: is transplant still needed?

Andy I Chen.

DOI: https://doi.org/10.1182/blood.2026033265
Am J Hematol. 2026 Apr 25.

Cladribine With Low-Dose Cytarabine and Venetoclax Alternating With Azacitidine and Venetoclax for Newly Diagnosed Acute Myeloid Leukemia.

Tapan M Kadia, Alex Bataller, Alexandre Bazinet, Gautam Borthakur, Naval Daver, Nicholas J Short, Courtney DiNardo, Elias Jabbour, Caitlin R Rausch, Ghayas C Issa, Naveen Pemmaraju, Maro Ohanian, Abhishek Maiti, Guillermo Montalban-Bravo, Koji Sasaki, Ian M Bouligny, Musa Yilmaz, Fadi G Haddad, Lucia Masarova, Kelly Chien, Yesid Alvarado, Nitin Jain, Uday Popat, Elizabeth Shpall, Sanam Loghavi, Wei Qiao, Xuemei Wang, Guillermo Garcia-Manero, Farhad Ravandi, Hagop M Kantarjian.

Venetoclax-based low-intensity regimens have improved the outcomes of older or unfit patients with acute myeloid leukemia (AML). This phase II study investigated the combination of cladribine plus low-dose cytarabine and venetoclax alternating with azacitidine plus venetoclax for older or unfit patients with newly diagnosed AML. A total of 190 patients were included; the median age was 68 years (range, 47-84 years; 13% ≥ 75 years). By the European LeukemiaNet 2022 classification, 16%, 20%, and 64% were stratified as favorable, intermediate, and adverse risk, respectively. The rates of complete remission (CR)/CR with incomplete blood count recovery (CRi) and minimal residual disease (MRD) negative CR/CRi were 84% and 75% overall and 91% and 77% among patients with TP53-wild type AML, respectively. The 4- and 8-week mortality rates were 1% and 3%, respectively. Among responders, 44% proceeded to allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) and event free survival (EFS) were 52 and 50 months, respectively. The 2- and 5-year OS rates were 60% and 45%, respectively. The 2-and 5-year EFS rates were 56% and 43%, respectively. Patients achieving MRD-negative CR had a median OS not reached and a 2-year OS rate of 70%. The median time to absolute neutrophil count recovery (> 1 × 109/L) and platelet count recovery (> 100 × 109/L) after induction was 27 and 24 days, respectively. Overall, the treatment was safe and most grade 3 and 4 adverse events were infectious complications. The combination produced a high rate of remissions, translating into favorable outcomes for older patients with newly diagnosed AML. Trial Registration: ClinicalTrials.gov idetifier: NCT03586609.

DOI: https://doi.org/10.1002/ajh.70328
Hematol Rep. 2026 Apr 13. pii: 28. [Epub ahead of print]18(2):

Asciminib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Case Series and Review of Emerging Evidence.

Mostafa F Mohammed Saleh, Abdulrahman Nasiri, Ahmed Kotb Abdrabou, Hadeel Samarkandi, Ayman Saad, Mahmoud Aljurf, Amr Hanbali, Ali Alahmari.

  Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) remains a high-risk entity despite advances in tyrosine kinase inhibitors (TKIs), immunotherapy, and cellular therapies. Relapse driven by clonal evolution, central nervous system (CNS) sanctuary disease, and TKI resistance, particularly T315I mutations, continues to limit durable disease control. Asciminib, a first-in-class allosteric BCR::ABL1 (STAMP) inhibitor, has demonstrated efficacy and favorable tolerability in chronic myeloid leukemia, but its optimal role in Ph+ ALL remains to be defined. We report a three-patient case series of Ph+ acute leukemia treated with asciminib across diverse high-risk clinical settings, including multiply relapsed disease, CNS involvement, T315I-mutated leukemia, post-CAR-T-cell relapses, and transplant bridging. Clinical outcomes are contextualized through a comprehensive review of emerging clinical trial data, real-world cohorts, and mechanistic studies evaluating asciminib in Ph+ ALL. Across all cases, asciminib was incorporated as part of combination or consolidation strategies rather than as monotherapy in active disease. Asciminib contributed to molecular disease control, CNS leukemia clearance, and successful bridging to allogeneic transplantation or cellular therapy, with acceptable tolerability and no major vascular toxicity. Integration of published evidence demonstrates that asciminib exhibits consistent biological activity in Ph+ ALL, with improved durability when used in rational combinations, particularly with immunotherapy or ATP-competitive TKIs. Preclinical data further support asciminib's compatibility with antibody-based and cellular therapies through preservation of immune effector function. Asciminib represents a versatile but context-dependent therapeutic option in Ph+ ALL. Its greatest clinical value appears to lie in rational combination regimens, maintenance strategies, and bridging to definitive therapies rather than single-agent salvage. Emerging structural biomarkers and ongoing clinical trials are expected to further refine patient selection, sequencing, and optimal integration of asciminib, particularly in CNS-involved disease and post-CAR-T cell relapse.

Keywords:  ABL1 inhibition; BCR; Philadelphia chromosome-positive acute lymphoblastic leukemia; asciminib; relapsed/refractory disease

DOI:  https://doi.org/10.3390/hematolrep18020028
Blood. 2026 May 01. pii: blood.2025032145. [Epub ahead of print]

How I Treat Plasma Cell Leukemia.

Samer Al Hadidi, Frits van Rhee, Larry D Anderson.

Plasma cell leukemia (PCL) represents an exceptionally aggressive plasma cell malignancy defined by ≥5% circulating plasma cells in peripheral blood of patients otherwise meeting diagnostic criteria for multiple myeloma (MM), per International Myeloma Working Group consensus. This ultra-high-risk disease exhibits distinctive clinical features including frequent extramedullary involvement, severe cytopenias, hypercalcemia, renal insufficiency, and/or significantly elevated β2-microglobulin and lactate dehydrogenase levels. The molecular landscape includes high-risk cytogenetic abnormalities and mutations that promote accelerated proliferation, apoptotic resistance, immune evasion, and bone marrow microenvironmental independence through dysregulated adhesion molecule and chemokine receptor expression. While autologous stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies improved historical outcomes, the therapeutic paradigm continues to evolve. Novel therapeutic approaches including B-cell maturation antigen (BCMA)-directed therapies (bispecific antibodies and chimeric antigen receptor T-cell therapy), GPRC5D-targeted therapy, and BCL-2 inhibition demonstrate promise in treating both primary and secondary PCL. Despite these advances, PCL remains inadequately studied, with treatment approaches predominantly extrapolated from MM trials where PCL patients have largely been excluded. This review synthesizes current evidence and presents illustrative clinical cases demonstrating practical treatment approaches, while highlighting critical knowledge gaps requiring dedicated prospective clinical trials to meaningfully improve outcomes in this challenging disease entity.

DOI: https://doi.org/10.1182/blood.2025032145
Drugs. 2026 Apr 28.

Sonrotoclax: First Approval.

Hannah A Blair.

Sonrotoclax (Baiyueda®), a small-molecule B-cell lymphoma-2 (BCL-2) inhibitor, is being developed by BeOne Medicines for the treatment of various B-cell malignancies. On 6 January 2026, sonrotoclax received conditional approval in China for adult patients with chronic lymphocytic leukaemia (CLL)/small lymphocytic leukaemia (SLL) who have previously received at least one systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor, and adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have previously received at least two systemic therapies, including a BTK inhibitor. This article summarizes the milestones in the development of sonrotoclax leading to this first approval for the second-line treatment of relapsed/refractory CLL/SLL and MCL.

DOI: https://doi.org/10.1007/s40265-026-02322-0
Indian J Hematol Blood Transfus. 2026 May;42(3): 1044-1048

Inferior Outcomes of p230-CML with Imatinib: a Report of 2 Cases of p210/p230 Co-Expressed CML Showing Rapid Progression To Leukaemia Cutis along with the Systematic Review.

Ankur Jain, Sumita Chaudhry, Monica Sharma, J M Khunger.

  Due to its rarity, no large studies have evaluated the outcomes of p230-CML patients treated with tyrosine kinase inhibitors (TKI). We describe the clinical course of two patients with p210/p230 co-expressed CML and provide a comprehensive review of 65 cases of p230-CML. Case-1 was a 35-year old male diagnosed with p210/p230-CML in chronic phase (CP) who progressed to extramedullary blast crises (EMBC) in the form of leukemia cutis (LC) after 4-years of imatinib therapy. TK domain (TKD) mutation was negative. Treatment with dasatinib resulted in resolution of LC, but patient defaulted treatment and died. Case-2 was a 25-year old male with p210/p230-CML in accelerated phase (AP) who progressed to EMBC-LC (T315I+) after 1-year of imatinib therapy. He responded transiently to dasatinib, but succumbed to progressive disease. Literature review revealed that patients with p230-CML had female predominance, a lower total leucocyte count and higher platelets at presentation than p210-CML. About 18% had extreme thrombocytosis (> 1000 × 109/L) and 29.5% had additional cytogenetic abnormalities at diagnosis. The proportion of transformations to AP/BC (30% vs. 25%) and deaths (37.5% vs. 27%) was similar in the pre-TKI and TKI era. As compared to imatinib, frontline treatment with 2nd -generation TKI improved the median survival.
Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-025-02151-3.

Keywords:  Dasatinib; E19a2 CML; Extramedullary blast crises; T315I

DOI:  https://doi.org/10.1007/s12288-025-02151-3
Hematol Oncol. 2026 May;44(3): e70194

Zanubrutinib in Hairy Cell Leukemia Variant: Clinical Report and Overview of BTK Inhibition in Variant Disease.

A Bernardelli, E Carazzai, I Mion, N Serafin, I Ferrarini, M Krampera, C Visco.

  Hairy cell leukemia variant (HCL-v) is a rare B-cell malignancy with limited treatment options in relapsed or refractory settings. We describe the first reported case of chemo-refractory HCL-v successfully treated with zanubrutinib monotherapy. An 84-year-old man, previously refractory to rituximab and bendamustine, achieved early hematologic improvement and reduction in spleen size after starting zanubrutinib, with a sustained clinical and laboratory response at 17 months. A clinical study with ibrutinib has shown durable disease control in classic and variant HCL, supporting BTK inhibition as a therapeutic strategy. This case suggests zanubrutinib as a promising chemo-free option for frail HCL-v patients.

Keywords:  BTK inhibition; hairy cell leukemia variant; targeted therapy; zanubrutinib

DOI:  https://doi.org/10.1002/hon.70194
Ann Hematol. 2026 Apr 25. pii: 267. [Epub ahead of print]105(5):

Impact of the diagnosis-to-treatment interval on the survival of patients with CD5-positive diffuse large B-cell lymphoma.

Yuma Nato, Kana Miyazaki, Dai Maruyama, Hiroyuki Takahashi, Kazutaka Sunami, Eiju Negoro, Satsuki Murakami, Takahiro Okada, Nobuyuki Takayama, Yuri Miyazawa, Ilseung Choi, Shuji Momose, Yuto Kaneda, Masahiro Yoshida, Naoto Tomita, Tohru Murayama, Momoko Nishikori, Junji Hiraga, Kohtaro Toyama, Naoki Takahashi, Taro Masunari, Jun Takizawa, Isao Tawara, Naoko Asano, Koichi Ohshima, Koji Izutsu, Koji Kato, Ritsuro Suzuki, Motoko Yamaguchi.



Keywords:  CD5 antigen; DA-EPOCH-R; Diagnosis-to-treatment interval; Diffuse large B-cell lymphoma

DOI:  https://doi.org/10.1007/s00277-026-07021-0
Int J Lab Hematol. 2026 Apr 30.

Role of Flow Cytometric Enumeration of Circulating hMICL (CD371) Positive Leukemic Stem Cells in Diagnosis and Prognostication of BCR::ABL1-Negative Myeloproliferative Neoplasms.

Gurleen Oberoi, Rishi Dhawan, Jasmita Dass, Neha Ganju, Ganesh Viswanathan, Suman Lata, Mukul Agarwal, Pradeep Kumar Kumar, Tulika Seth, Manoranjan Mahapatra, Renu Saxena.

   BACKGROUND: BCR-ABL1-negative myeloproliferative neoplasms (MPNs) often exhibit overlapping clinical and morphological features, making accurate subcategorization challenging. The h-MICL (CD371) antigen, selectively expressed on leukemic stem cells (LSCs) and absent on CD34+CD38- cells in normal or regenerating marrow, represents a potential diagnostic and prognostic marker.
OBJECTIVES: This study aimed to evaluate the diagnostic utility of circulating CD34+CD38-h-MICL+ cells in subtyping BCR-ABL1-negative MPNs and to assess their correlation with the Dynamic International Prognostic Scoring System (DIPSS) score. Additionally, to identify a cut-off value of CD34+CD38-h-MICL+ cells that can effectively differentiate PMF.
METHODS: Fifty-four patients with BCR-ABL1-negative MPNs were prospectively enrolled at a tertiary care center in North India over 18 months. Peripheral blood was analyzed via flow cytometry to quantify CD34+, CD34+CD38+, CD34+CD38-, and CD34+CD38-h-MICL+ cell subsets.
RESULTS: A significant increase in circulating CD34+CD38-h-MICL+ cells was observed in patients with overt MF (median 2.8%), prefibrotic MF (4.15%), and post-PV/ET MF (3%) compared to PV and ET (median 0%; p < 0.001). A threshold of ≥ 0.9% CD34+CD38-h-MICL+ cells effectively identified MF cases with 88% sensitivity and 89% specificity. Moreover, a positive correlation was found between the percentage of CD34+CD38-h-MICL+ cells and DIPSS score (ρ = 0.41, p = 0.036), with every 1.72% increase in this cell population corresponding to a 1-point rise in DIPSS score.
CONCLUSION: Circulating CD34+CD38-h-MICL+ cells represent a promising biomarker; their quantification may aid in subclassification, particularly in distinguishing prefibrotic MF from ET, and may serve as a potential target for future therapeutic strategies. Further validation in larger cohorts is warranted.

Keywords:  diagnosis; flow cytometry; myeloproliferative neoplasm (MPN); prognosis; subclassification

DOI:  https://doi.org/10.1111/ijlh.70128
Rev Med Interne. 2026 Apr 30. pii: S0248-8663(26)00531-X. [Epub ahead of print]

French protocol for the diagnosis and management of autoimmune hemolytic anemia in adults.

Marc Michel, Sylvain Audia, Bernard Bonnotte, Thibault Comont, Etienne Crickx, Mikael Ebbo, Lionel Galicier, Delphine Gobert, Olivier Lambotte, Matthieu Mahevas, Jean Marie Michot, Guillaume Moulis, Marc Ruivard, Louis Terriou, Bertrand Godeau.

  Autoimmune hemolytic anaemias (AIHAs) represent different subtypes of a rare autoimmune disease in which autoantibodies targeting autoantigens expressed on autologous red blood cells' (RBCs) membrane are produced, leading to their accelerated destruction. In the presence of hemolytic anaemia, the direct antiglobulin test (DAT) is the cornerstone of AIHA diagnosis. AIHAs are classified according to the isotype and the thermal optimum of the autoantibody, into warm (wAIHAs), cold and mixed AIHAs. wAIHAs, by far the most frequent type of AIHAs, are associated with underlying conditions in ∼50% of cases. Among adults, cold AIHAs include cold agglutinin disease (CAD), and cold agglutinin syndrome (CAS) when there is an underlying condition. Both CAD and CAS are IgM cold-antibody driven AIHAs characterized by classical complement pathway-mediated hemolysis. The management of AIHAs which has has long been empirical is mostly based on corticosteroids±rituximab for wAIHAs and on rituximab±bendamustine for CAD requiring to be treated, complement inhibition with sutimlimab being a new therapeutic option for CAD. This article reporting the French guidelines focused on diagnosis and treatment of adult AIHAs is adapted from the last update of the Protocole National de Diagnostic et de Soins (French protocol for diagnosis and management). These guidelines have been set up and led by the French national center for adult' immune cytopenias (CeReCAI).

Keywords:  AHAI réfractaires; Adult autoimmune hemolytic anemias; Anémie hémolytique auto-immune de l’adulte; Anémie hémolytique auto-immune à anticorps chauds; Cold agglutinin disease; Cold agglutinin syndrome; Direct antiglobulin test; Formes secondaires; Guidelines; Maladie des agglutinines froides; Management; Protocol for diagnosis and management; Protocole national de diagnostic et des soins (PNDS); Refractory AIHAs; Rituximab; Syndrome des agglutinines froides; Test direct à l’antiglobuline; Traitement des AHAI

DOI:  https://doi.org/10.1016/j.revmed.2026.04.003
Am J Hematol. 2026 Apr 25.

Multicenter Real-World Analysis of Glofitamab in Relapsed/Refractory Primary CNS Lymphoma: Clinical Activity, CNS Penetration, and ctDNA Dynamics.

Apeng Yang, Jinfeng Dong, Xiaofang Deng, Hui Liu, Zhenying Chen, Junfang Lin, Qincheng Che, Qiaoxian Lin, Guilan Lai, Meihong Zheng, Xiaoqiang Zheng, Qingjiao Chen, Jizhen Wang, Junmin Chen, Youwen He, Zhiyong Zeng.

  Therapeutic options for relapsed/refractory (R/R) primary CNS lymphoma (PCNSL) are limited, and the clinical activity and central nervous system (CNS) pharmacology of CD20 × CD3 bispecific antibody glofitamab remain poorly defined. This multicenter real-world study evaluated the efficacy, CNS penetration, and molecular response dynamics of glofitamab in 16 adults with R/R PCNSL treated with glofitamab monotherapy. Paired plasma and cerebrospinal fluid (CSF) samples were analyzed to assess CNS drug penetration. Serial CSF circulating tumor DNA (ctDNA) profiling was performed during glofitamab monotherapy, and chimeric antigen receptor T (CAR-T) cell kinetics were examined in patients receiving CAR-T consolidation. Glofitamab monotherapy achieved an interim overall response rate of 75%, including 50% complete responses. Median progression-free survival was 15.4 months, and median overall survival was not reached. In several patients, glofitamab was used as a bridge to subsequent CAR-T and/or autologous stem cell transplantation (ASCT), which may have influenced long-term outcomes. Glofitamab was detectable in the CSF of 60% of patients, with CSF/plasma ratios up to 0.44%. Longitudinal ctDNA analysis demonstrated that early molecular clearance was associated with radiographic response, while persistent or re-emergent ctDNA preceded clinical progression. The safety profile of glofitamab monotherapy was manageable, with most adverse events being Grade 1-2. Two patients (11%) experienced Grade ≥ 3 neurotoxicity and recovered after corticosteroid treatment. Two additional patients developed fatal immune effector cell-associated neurotoxicity syndrome following CAR-T consolidation. Glofitamab demonstrates early clinical activity and measurable CNS penetration in R/R PCNSL. Serial CSF ctDNA profiling may aid treatment monitoring, warranting prospective validation.

Keywords:  bispecific antibody; circulating tumor DNA; glofitamab; pharmacokinetics; primary CNS lymphoma

DOI:  https://doi.org/10.1002/ajh.70342