bims-hemali 2026-04-19 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2026–04–19
seventeen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Does minimal residual disease matter in t(11;14) myeloma?
Zanubrutinib and pirtobrutinib show synergistic killing and suppression of BTK signaling in MYD88-mutated lymphoma cells.
The Role of Allogeneic Hematopoietic Cell Transplantation in the Management of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors.
Acalabrutinib in Waldenström macroglobulinemia yields durable responses with 5 years of follow-up.
CAR-T therapy moving to first-line in multiple myeloma: latest updates from the 2025 ASH annual meeting.
Interim assessment by circulating tumor DNA in primary mediastinal large B-cell lymphoma: a multicenter LYSA study.
Updated consensus guidelines for the diagnosis and management of patients with hairy cell leukemia (HCL) and HCL-variant.
Point: CAR-T therapy is the preferred option in relapsed/refractory multiple myeloma.
Evolving therapeutic strategies in mantle cell lymphoma: advancements and future directions.
Historical outcomes for patients with stage IA NLPHL: RGlobal nLPHL One Working Group (GLOW) retrospective analyses.
Aging cells, young patients: senescence in Hodgkin lymphoma.
Lenalidomide-rituximab or lenalidomide-rituximab-bendamustine for relapsed/refractory follicular lymphoma: primary and final analysis of the randomized phase II HOVON110/ReBeL study.
A Novel CIP2A and BCL-XL Clinical Diagnostic Toolkit to Predict Disease Progression and Treatment-Free Remission in Chronic Myeloid Leukaemia.
Avapritinib achieves long-term disease control with favorable safety in patients with indolent systemic mastocytosis over 3 years.
Comparative Outcomes of Consolidation Strategies After R-MVP Induction in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System.
[Blastoïd mantle cell lymphoma, TdT-positive: Toward a more juvenile profile?]
A Phase 2, Open-Label, Multicenter Study of the Safety and Efficacy of TAK-007 in Adult Patients with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma.

Blood. 2026 Apr 16. 147(16): 1787-1788

Does minimal residual disease matter in t(11;14) myeloma?

Cyrille Touzeau, Jill Corre.

DOI: https://doi.org/10.1182/blood.2025032941
Blood Adv. 2026 Apr 15. pii: bloodadvances.2025018126. [Epub ahead of print]

Zanubrutinib and pirtobrutinib show synergistic killing and suppression of BTK signaling in MYD88-mutated lymphoma cells.

Dominic Pizzarella, Amanda Kofides, John M Hatcher, Xia Liu, Alberto Guijosa, Nickolas Tsakmaklis, Abigail Peachey, Jinhua Wang, Maria Luisa Guerrera, Christopher J Patterson, Zachary R Hunter, Hao Sun, Shayna Sarosiek, Jorge J Castillo, Sara Buhrlage, Sirano Dhe-Paganon, Andrew R Branagan, Steven P Treon, Shirong Liu.

DOI: https://doi.org/10.1182/bloodadvances.2025018126
Am J Hematol. 2026 Apr 15.

The Role of Allogeneic Hematopoietic Cell Transplantation in the Management of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors.

Ivan Pasic, Jeffrey H Lipton.

  Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL), the most common subtype of adult ALL, has undergone dramatic transformation in prognosis over the past two decades. Introduction of tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 fusion protein has revolutionized frontline therapy, with successive generations of TKIs-from imatinib to dasatinib and most recently ponatinib-achieving progressively deeper and more durable molecular responses. Concurrently, the integration of immunotherapy, particularly blinatumomab, has enabled chemotherapy-sparing approaches further improving tolerability and efficacy. These advances have fundamentally challenged the historical paradigm that allogeneic hematopoietic cell transplantation (HCT) is indispensable for all Ph+ ALL patients in first complete remission. The role of allogeneic HCT is often debated and increasingly individualized, guided by measurable residual disease (MRD) assessment, TKI generation, depth and duration of molecular response, and patient-specific factors. Emerging data suggest that a subset of patients achieving early, deep MRD negativity with TKIs and immunotherapy may achieve durable remissions without transplant, though long-term follow-up remains limited. For patients proceeding to allogeneic HCT, optimization of transplant strategy-including donor selection, conditioning intensity, graft-versus-host disease prophylaxis, and posttransplant TKI maintenance-is critical to maximize graft-versus-leukemia effects while minimizing toxicity. Treatment-free remission strategies following prolonged TKI maintenance in non-transplant patients, and the integration of chimeric antigen receptor (CAR) T-cell therapy as bridge, consolidation, or salvage, represent emerging frontiers. This review critically examines the contemporary role of allogeneic HCT in Ph+ ALL and provides a framework for transplant decision-making in the contemporary era of targeted and cellular immunotherapy.

Keywords:  Ph+ acute lymphoblastic leukemia; allogeneic hematopoietic cell transplant; tyrosine kinase inhibitor

DOI:  https://doi.org/10.1002/ajh.70330
Blood Adv. 2026 Apr 15. pii: bloodadvances.2025017713. [Epub ahead of print]

Acalabrutinib in Waldenström macroglobulinemia yields durable responses with 5 years of follow-up.

Roger G Owen, Helen McCarthy, Shirley D'Sa, Sheeba K Thomas, Olivier Tournilhac, Francesco Forconi, Marie José Kersten, Pier Luigi Zinzani, Sunil Iyengar, Jaimal Kothari, Monique C Minnema, Efstathios Kastritis, Bruce David Cheson, Harriet Sarah Walter, Daniel Greenwald, Roser Calvo, Yi Li, Simon Rule, Richard R Furman.

Acalabrutinib is a covalent Bruton tyrosine kinase inhibitor. In the phase 2 ACE-WM-001 trial (NCT02180724), at 27.4 months median follow-up, acalabrutinib yielded durable responses in patients with treatment-naive (TN) or relapsed/refractory (R/R) Waldenström macroglobulinemia (WM). We report WM-001 results at 63.7 months median follow-up. Overall, 106 patients (TN, n = 14; R/R, n = 92) were treated; 52.8% discontinued treatment (TN, n = 7; R/R, n = 49), most commonly due to disease progression (19.8%; TN, n = 1; R/R, n = 20) and adverse events (AEs; 17.9%; TN, n = 4; R/R, n = 15). Overall response rates were 92.9% and 94.6%, and major response rates (≥ partial response) were 78.6% and 81.5% in the TN and R/R cohorts, respectively. Median progression-free survival (PFS) was not estimable (NE; 95% CI: 19.3, NE) and 67.5 months (53.3, NE), with estimated 66-month PFS rates of 83.6% (48.0, 95.7) and 52.0% (39.3, 63.2) in the TN and R/R cohorts, respectively. Median duration of response (DOR) was not reached (NR) (11.9 months, NE) and 64.7 months (54.5, NE), with estimated 66-month DOR rates of 90.0% (47.3, 98.5) and 44.8% (27.1, 61.1) in the TN and R/R cohorts, respectively. Median overall survival (OS) was NR in both cohorts; estimated 66-month OS rates were 90.9% (50.8, 98.7) and 71.2% (60.3, 79.6), respectively. Cardiac events of clinical interest occurred in 22 (20.8%) patients. One grade 5 AE (intracranial hematoma) was considered treatment-related. With 5 years of follow-up, efficacy and safety of acalabrutinib in WM were maintained.

DOI: https://doi.org/10.1182/bloodadvances.2025017713
J Hematol Oncol. 2026 Apr 13. pii: 25. [Epub ahead of print]19(1):

CAR-T therapy moving to first-line in multiple myeloma: latest updates from the 2025 ASH annual meeting.

Chuanying Geng, Wenming Chen, Hong-Hu Zhu.

  CAR-T therapy is rapidly reshaping the treatment paradigm of multiple myeloma (MM). At the 2025 ASH Annual Meeting, pivotal trials demonstrated marked efficacy across both relapsed/refractory and newly diagnosed settings. In KarMMa-3, a subgroup analysis of older patients (≥ 70 years) showed idecabtagene vicleucel significantly improved outcomes versus standard care: overall response rate (ORR) 81.6% vs. 48.1%, median progression-free survival (PFS) 18.9 vs. 5.7 months, with median overall survival (OS) not reached in either arm. CARTITUDE-4 showed superior 30-month PFS (71.0% vs. 43.2%), while iMMagine-1 reported an ORR of 97% with 93% minimal residual disease negativity. Notably, frontline CAR-T studies achieved unprecedented outcomes, including 100% ORR, stringent complete response rates approaching 94-97%, and 30-month PFS and OS rates of 88-92%. Together, these data support a paradigm shift toward earlier integration of CAR-T therapy in MM management.

Keywords:  2025 ASH; CAR-T; Cell therapy; Multiple myeloma

DOI:  https://doi.org/10.1186/s13045-026-01793-8
Blood Adv. 2026 Apr 14. pii: bloodadvances.2025019108. [Epub ahead of print]

Interim assessment by circulating tumor DNA in primary mediastinal large B-cell lymphoma: a multicenter LYSA study.

Vincent Camus, Daphné Krzisch, Alessio Bruscaggin, Emilie Lévêque, Mathieu Viennot, Luc-Matthieu Fornecker, Morgane Cheminant, Sebastien Bailly, Franck Morschhauser, Pierre Feugier, Sylvain Choquet, Eric Durot, Sylvain Carras, Caroline Delette, Ghandi Damaj, Agathe Waultier Rascalou, Pierre Lebreton, Katell Le Dû, Jean Galtier, Roch Houot, Nadine Morineau, Kamel Laribi, Laure Lebras, Lucie Obéric, Sandy Amorim, Simone Bocchetta, Pierre-Julien Viailly, Vinciane Rainville, Philippe Ruminy, Mélody Caillot, Lodovico Terzi di Bergamo, Deborah Piffaretti, Maria Cristina Pirosa, Matin Salehi, Gabriela Forestieri, Fanny Drieux, Elena-Liana Veresezan, Alexandra Traverse-Glehen, Marie Donzel, Lucie Burel, Elodie Bohers, Marie-Delphine Lanic, Dominique Penther, Stéphanie Becker, Pierre Decazes, David Tonnelet, Simon Draye-Carbonnier, Hervé Tilly, Fabrice Jardin, Davide Rossi, Pierre Sesques.

Primary mediastinal large B-cell lymphoma (PMBL) achieves excellent outcomes with dose-dense immunochemotherapy, yet response assessment by PET remain limited. In this prospective multicenter observational study, we evaluated the clinical relevance of circulating tumor DNA (ctDNA) minimal residual disease (MRD) in newly diagnosed PMBL patients and assessed whether MRD enhances outcome discrimination beyond PET. Plasma and PET images were collected at baseline and after 2 and 4 cycles. ctDNA and tumor biopsy were analyzed by high-depth, error-corrected sequencing (limit of detection ~10⁻³). Associations between MRD, PET response and progression-free survival (PFS) were evaluated. Among 84 patients, baseline ctDNA was detected in 98%. After four cycles of treatment with R-CHOP14 or R-ACVBP, 87.7% had undetectable MRD. Persistence of MRD after four cycles of therapy was associated with shorter PFS (HR = 78.1 [95% CI: 9.5-641.8]). The 1-year PFS was 98.4% [95.4-100] for patients with undetectable MRD4 vs. 33.3% [13.2-84] for patients with detectable MRD4 (p<10⁻⁴). MRD4 showed a higher positive predictive value (89% vs. 50%) for disease progression than PET4, maintaining a similar negative predictive value (100% vs. 93%). In multivariate analysis, only PET4(-)/MRD4(-) remained associated with PFS (adjusted HR = 0.07 [95% CI: 0.01-0.90]). Plasma ctDNA represents a highly abundant source of genetic markers for tumor fingerprinting and disease monitoring. MRD detection following frontline therapy strongly complements PET response criteria in predicting outcome. These findings support the use of ctDNA monitoring as a valuable tool for future risk-adapted strategies in PMBL. NCT04980222.

DOI: https://doi.org/10.1182/bloodadvances.2025019108
Blood. 2026 Apr 14. pii: blood.2025032757. [Epub ahead of print]

Updated consensus guidelines for the diagnosis and management of patients with hairy cell leukemia (HCL) and HCL-variant.

Clive S Zent, Enrico Tiacci, Robert J Kreitman, Tamar Tadmor, Martin S Tallman, Bernhard J Wörmann, Leslie A Andritsos, Evgeny Arons, Versha Banerji, Jacqueline Claudia Barrientos, Seema A Bhat, James S Blachly, Alessandro Broccoli, Timothy G Call, Claire Dearden, Judit Demeter, Sascha Dietrich, Dima El-Sharkawi, Andrei Fagarasanu, Brunangelo Falini, Francesco Forconi, Alina S Gerrie, Douglas E Gladstone, Alessandro Gozzetti, Paul Joseph Hampel, David J Hermel, Sunil Iyengar, James B Johnston, Gunnar Juliusson, Thomas J Kipps, Francesco Lauria, Gerard Lozanski, Sameer A Parikh, Jae H Park, Aaron Polliack, Graeme Quest, Kanti R Rai, Farhad Ravandi, Tadeusz Robak, Kerry A Rogers, Alan Saven, John F Seymour, Constantine S Tam, Xavier Troussard, Thorsten Zenz, Pier Luigi Zinzani, Michael Rhodes Grever.

Hairy cell leukemia (HCL) and hairy cell leukemia variant (HCLv) are distinct, rare, chronic splenic B cell lymphomas/leukemias that partially overlap in clinico-pathological presentation but differ in genetic basis, prognosis, and management. HCL is caused by the BRAF-V600E kinase-activating mutation in >95% of patients, usually has excellent responses to chemotherapy with purine analogs and is also amenable to BRAF inhibitor-based targeted treatments. In contrast, HCLv lacks BRAF-V600E, requires combined therapy with purine analogs plus rituximab and generally shows less-durable responses. Here, an international team of hematologists expert on these rare diseases was convened by the Hairy Cell Leukemia Foundation to update the previous guidelines (published in 2017) by providing a summary of current methods to diagnose and manage patients with HCL and HCLv, as well as a prospective on newer targeted therapies to further improve outcome.

DOI: https://doi.org/10.1182/blood.2025032757
Blood Adv. 2026 Apr 13. pii: bloodadvances.2026019898. [Epub ahead of print]

Point: CAR-T therapy is the preferred option in relapsed/refractory multiple myeloma.

Rahul Banerjee.

DOI: https://doi.org/10.1182/bloodadvances.2026019898
Leukemia. 2026 Apr 15.

Evolving therapeutic strategies in mantle cell lymphoma: advancements and future directions.

Rita Tavarozzi, Nawar Maher, Gioacchino Catania, Giulia Zacchi, Francesca D'Andrea, Antonella Sofia, Manuela Zanni, Marco Ladetto.

Mantle cell lymphoma (MCL) is a biologically and clinically heterogeneous B-cell malignancy with a historically poor prognosis. Recent advances have substantially expanded treatment options, particularly through the integration of targeted therapies, chemotherapy-free regimens, and cellular approaches. Frontline treatment now incorporates Bruton's tyrosine kinase inhibitors (BTKi) in combination with chemotherapy and in chemotherapy-free regimens. For patients with relapsed or refractory disease, particularly those previously exposed to BTKi, chimeric antigen receptor T-cell (CAR T) therapies and third-generation BTKi like pirtobrutinib provide highly effective options while several novel agents, including bispecific antibodies (bsAbs), are under investigation. Nevertheless, achieving long-lasting remissions is still a major challenge, especially among high-risk patients. Future directions include optimizing sequencing, refining rational combination therapies, expanding the application of bsAbs, and integrating small molecules and novel immunoconjugates to enhance therapeutic efficacy and long-term outcomes. This review provides an overview of the current and emerging therapies for MCL, highlighting how the integration of biological agents, strategic combinations, and patient-centered approaches are driving the next phase of MCL treatment.

DOI: https://doi.org/10.1038/s41375-026-02942-1
Blood Adv. 2026 Apr 14. pii: bloodadvances.2026020012. [Epub ahead of print]

Historical outcomes for patients with stage IA NLPHL: RGlobal nLPHL One Working Group (GLOW) retrospective analyses.

Jamie E Flerlage, Dennis A Eichenauer, Michael Fuchs, Sylvia Hartmann, Hans Theodor Eich, Kerry J Savage, Andrea C Lo, Brian Skinnider, Saad Akhtar, M Shahzad Rauf, Irfan Maghfoor, Chelsea C Pinnix, Raphael E Steiner, Sarah A Milgrom, Francisco Vega, Mohammed Alomari, Xiao-Yin Zhang, Graham P Collins, Ranjana H Advani, Priyadarshini Kumar, Michael J Dickinson, Andrew Wirth, Richard Tsang, Anca Prica, Ajay Major, Sonali M Smith, Peter G Hendrickson, Chris R Kelsey, David Hopkins, Pamela McKay, Andrea K Ng, Julie L Koenig, Louis S Constine, Carla Casulo, Gukan Sakthivel, Jonathan A Baron, John P Plastaras, Kenneth B Roberts, Sarah Gao, Jalila Al Kendi, Nasser Al Rahbi, Alexander George Balogh, Mario Levis, Umberto Ricardi, Akshay Sridhar, Pallawi Torka, Lena Specht, Ravindu De Silva, Nimish Shah, Keir Pickard, Wendy Osborne, Lindsay J Blazin, Michael Henry, Isabela Chang, Christine Moore Smith, Daniel Halperin, Fiona Miall, Jessica L Brady, N George Mikhaeel, Bernadette Brennan, Anthony Penn, Mariia Senchenko, Egor Vasilevich Volchkov, Marie Reeves, Bradford S Hoppe, Stephanie A Terezakis, Dipti Talaulikar, Roberta Della Pepa, Marco Picardi, Youlia Kirova, Paige Fergusson, Michael Northend, Eliza A Hawkes, Denise Lee, Nicole Wong Doo, Allison Barraclough, Stephen Opat, Chan Y Cheah, Ross Salvaris, Matthew Ku, Nada Hamad, Howard Mutsando, Aditya Tedjaseputra, Michael Gilbertson, Tamara Marconi, Nicholas Viiala, Monica Palese, Ananth G Shankar, Matthew J Maurer, Yasodha Natkunam, Kara M Kelly, Peter Borchmann, Richard T Hoppe, Michael S Binkley.

We evaluated outcomes by management type for patients with stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in the Global NLPHL One Working Group (GLOW) retrospective database of 2243 patients with stage I-IV disease diagnosed from 1992-2021 at 38 international institutions. 779 patients were stage IA with median age of 35 years (range=3-89) and median follow-up of 6.1 years. The 6-year PFS and OS were 86.3% and 97.7%, respectively. Outcomes were analyzed for two groups: complete resection and unresected disease. Patients with a complete resection and observation alone (n=99) had a 6-year PFS of 65.5% versus 90.5% for those who received RT (n=53). Patients with unresected disease (n=627; 80.5%) had a 6-year PFS of 62.0% for rituximab alone (n=31), 89.6% for RT alone (n=325), 76.8% for ABVD alone (n=40), and 94.3% for ABVD+RT (n=130). 127 patients relapsed (16.3%), of which 25 (19.7%) had transformation. Our analysis suggests 1) RT improves the PFS in patients with completely resected disease; 2) Rituximab or ABVD alone do not appear to achieve a durable response; 3) Chemotherapy was not observed to add additional PFS benefit when used in combination with RT. Thus, for stage IA NLPHL, RT alone is likely sufficient for definitive treatment.

DOI: https://doi.org/10.1182/bloodadvances.2026020012
Blood Adv. 2026 Apr 28. 10(8): 2765-2766

Aging cells, young patients: senescence in Hodgkin lymphoma.

Isabella Y Kong, Lisa Giulino-Roth, Christian Steidl.

DOI: https://doi.org/10.1182/bloodadvances.2025019439
Haematologica. 2026 Apr 16.

Lenalidomide-rituximab or lenalidomide-rituximab-bendamustine for relapsed/refractory follicular lymphoma: primary and final analysis of the randomized phase II HOVON110/ReBeL study.

Marie José Kersten, Martin Dreyling, Kim M Linton, Dana Chitu, Gerben J C Zwezerijnen, Sanne H Tonino, Marcel Kap, Roberto Liu, Christel Van Hooije, Martine E D Chamuleau, Hein P J Visser, Eva De Jongh, Erik A F Marijt, Maria B L Leys, Yavuz M Bilgin, Jan Dürig, Pamela McKay, Tjeerd Snijders, Andrew Pettitt, Monique C Minnema, Gabriele Prange-Krex, Marloes L H Cuijpers, Lara H Bohmer, Lidwine W Tick, Axel Florschutz, Matthijs Silbermann, Rob Fijnheer, Aart Beeker, Nelleke Tolboom, Cristina Mitea, Anne I J Arens, Sanne E Wiegers, Martijn W Heymans, Wolfram Klapper, Sarah E Coupland, Daphne De Jong, Jeanette K Doorduijn, Josée M Zijlstra.

The R2 (lenalidomide-rituximab) and R2 with bendamustine (R2B) regimens are both feasible in relapsed/refractory follicular lymphoma (R/R FL), but prospective phase II data on R2B are lacking. In this multinational, prospective, randomised, non-comparative trial, patients with R/R FL were randomised 1:1 to R2 (arm A) or R2B (arm B). Patients achieving CT-based partial or complete remission (PR/CR) received rituximab maintenance every 3 months for 2 years. Co-primary endpoints were investigator-assessed CR rates at end-of-induction (EOI) and severe toxicity rates. Between December 2014 and July 2019, 92 patients were randomized. The trial was stopped prematurely due to slow accrual. CR rates at EOI were 11.4% (95% CI [3.8, 24.6%]) for R2 and 15.2% (CI [6.3, 28.9%]) for R2B. With a median follow-up of 74 months, predefined severe toxicities occurred in 3 (6.8%; CI [1.4, 18.7%]) and 6 pts (13.0%, CI [4.9, 26.3%]) in Arm A and Arm B respectively, with 2 pneumonia-related deaths in arm A and no treatment-related deaths in arm B; 43% and 66% experienced any grade 3-4 AE (2%/7% grade 4). At 60 months, in arms A and B event free survival (EFS) was 39.5% (CI [25.1, 53.6%]) and 56.4% (CI [40.1, 69.3%]). Overall survival (OS) was excellent at 72.1% and 86.3%, respectively. R2 and R2B are both effective treatment regimens for R/R FL. While CT-based CR rates were low, treatment with R2B resulted in numerically longer median EFS and OS, but this was associated with higher toxicity.

DOI: https://doi.org/10.3324/haematol.2025.300152
Int J Mol Sci. 2026 Mar 25. pii: 2991. [Epub ahead of print]27(7):

A Novel CIP2A and BCL-XL Clinical Diagnostic Toolkit to Predict Disease Progression and Treatment-Free Remission in Chronic Myeloid Leukaemia.

Ammar A Basabrain, Gemma M Austin, Alison K Holcroft, Jane F Apperley, Richard E Clark, Shankar Varadarajan, Claire M Lucas.

  Biomarkers that predict disease progression and treatment-free remission (TFR) would be of significant clinical value in chronic myeloid leukaemia (CML). We have previously shown that CIP2A levels at diagnosis can identify patients at increased risk of progression. One mechanism by which CIP2A acts is through upregulation of the anti-apoptotic gene BCL-XL. In this study, we evaluated BCL-XL mRNA expression as a diagnostic biomarker using samples from the SPIRIT2 and DESTINY clinical trials. In SPIRIT2, which compared imatinib and dasatinib as first-line therapies, high BCL-XL expression was associated with treatment failure, poor early molecular response, and lower rates of MR2 and MR3 achievement in patients treated with imatinib. In the DESTINY trial, which assessed treatment de-escalation and discontinuation, BCL-XL expression was significantly higher in patients who experienced molecular relapse compared to those achieving sustained TFR. Notably, increases in BCL-XL were detectable 6 to 8 months prior to molecular relapse, suggesting it may serve as an early biomarker of unsuccessful TFR. We now propose a clinical diagnostic toolkit combining CIP2A and BCL-XL biomarkers to stratify CML patients by the risk of disease progression and likelihood of achieving successful TFR.

Keywords:  BCL-XL; BCR::ABL1; CIP2A; CML; DESTINY; MR2 and MR3); SPIRIT2; biomarker; clinical trial; dasatinib; imatinib; molecular responses (EMR; treatment failure; treatment-free remission (TFR)

DOI:  https://doi.org/10.3390/ijms27072991
J Allergy Clin Immunol. 2026 Apr 13. pii: S0091-6749(26)00253-8. [Epub ahead of print]

Avapritinib achieves long-term disease control with favorable safety in patients with indolent systemic mastocytosis over 3 years.

Cem Akin, Vito Sabato, Jason Gotlib, Jens Panse, Ivan Alvarez-Twose, Deepti H Radia, Cristina Bulai Livideanu, Joseph Jurcic, Hanneke Oude Elberink, Paul Van Daele, Sonia Cerquozzi, Ingunn Dybedal, Andreas Reiter, Thanai Pongdee, Stéphane Barete, Celalettin Ustun, Philippe Schafhausen, Peter Vadas, Prithviraj Bose, Daniel J DeAngelo, Lindsay Rein, Pankit Vachhani, Massimo Triggiani, Patrizia Bonadonna, Karin Hartmann, Sigurd Broesby-Olsen, Mattias Mattsson, Tracy I George, William Shomali, Matthew Giannetti, Frank Siebenhaar, Hui-Min Lin, Ilda Bidollari, Benjamin Lampson, Janet Hong, Ashley Doyle, Tsewang Tashi, Mariana Castells.

   BACKGROUND: Indolent systemic mastocytosis (ISM), a clonal mast cell disease primarily driven by the KIT D816V mutation, can cause long-term debilitating symptoms and poor quality of life. Most patients rely on symptom-directed best supportive care medications, which do not treat the underlying driver of ISM. Avapritinib, an oral, potent, selective KIT D816V inhibitor, is approved in adults with ISM.
OBJECTIVE: We sought to understand the long-term efficacy and safety of avapritinib in ISM.
METHODS: The PIONEER trial (NCT03731260) enrolled adults with moderate to severe ISM symptoms. Patients initiated avapritinib 25 mg once daily (QD; recommended dose) plus best supportive care in part 1, 2, or 3; open-label part 3 is ongoing with up to 5 years of follow-up. As per investigator discretion and disease burden, a dose increase up to avapritinib 50 mg QD was permitted in part 3.
RESULTS: As of February 21, 2025, 226 patients initiated avapritinib at 25 mg QD. The median (range) treatment duration was 40.0 (0.7-67.2) months. Patients receiving avapritinib experienced durable and clinically meaningful symptom improvement (mean change, -19.39 [n = 127] in the Indolent Systemic Mastocytosis Symptom Assessment Form total symptom score) through approximately 3 years. Avapritinib continued to be well tolerated for a long-term with a safety profile comparable with the previously reported placebo-controlled portion. Most treatment-related adverse events (TRAEs) were grades 1 to 2, with limited grade 3 or higher reported. Edema events were the most frequent TRAEs (mostly grade 1). Serious TRAEs occurred in 3 patients (1%), and 7 patients (3%) discontinued treatment because of TRAEs.
CONCLUSIONS: Long-term follow-up (median, ∼3 years) demonstrates that avapritinib is effective and well tolerated. Avapritinib shows a favorable benefit-risk profile as a chronic ISM treatment.

Keywords:  Avapritinib; KIT D816V; KIT inhibitor; PIONEER study; efficacy; indolent systemic mastocytosis; long-term; quality of life; safety; systemic mastocytosis

DOI:  https://doi.org/10.1016/j.jaci.2026.04.001
Cancer Med. 2026 Apr;15(4): e71806

Comparative Outcomes of Consolidation Strategies After R-MVP Induction in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System.

Sang-A Kim, Jung Sun Kim, Ji Yun Lee, Joo Ho Lee, Keun-Yong Eom, Chul-Kee Park, Chae-Yong Kim, Dae Seog Heo, Jeong-Ok Lee, Tae Min Kim.

   BACKGROUND: The optimal consolidation strategy following high-dose methotrexate (MTX)-based induction in primary central nervous system lymphoma (PCNSL) remains controversial. This study compared real-world outcomes of different consolidation modalities in patients responsive to rituximab, MTX, vincristine, and procarbazine (R-MVP) induction chemotherapy.
METHODS: We retrospectively analyzed 296 newly diagnosed PCNSL patients treated with R-MVP between 2008 and 2023. Among 290 evaluable patients, the overall response rate (ORR) was assessed, and survival outcomes were evaluated by Kaplan-Meier and Cox regression analyses. Propensity score matching (PSM) was performed to compare autologous stem-cell transplantation (ASCT) and whole-brain radiotherapy (WBRT).
RESULTS: The ORR was 89.7%, with 71.7% achieving complete response (CR) or complete response unconfirmed (CRu) and 17.9% partial response (PR). Of 260 responders, 190 received consolidation: WBRT (40.8%), ASCT (20.0%), or non-myelosuppressive chemotherapy (NMC; 12.3%). After a median follow-up of 45.3 months, median progression-free survival (PFS) and overall survival (OS) for responders were 65.8 (95% CI 50.7-80.8) and 84.6 months (95% CI 66.5-102.7), respectively. ASCT yielded the most favorable survival (median PFS not reached), followed by WBRT (70.8 months), whereas NMC and no-consolidation groups showed significantly inferior PFS (22.9 and 40.1 months, p < 0.001). OS showed a similar trend (p = 0.006). On multivariable analysis, elevated LDH and consolidation type were independent predictors of PFS, whereas age and consolidation type were significant prognostic factors for OS. In the PSM cohort (ASCT vs. WBRT, n = 52 each), median PFS was not reached for ASCT versus 90.0 months for WBRT (p = 0.050); OS was not reached versus 97.9 months (p = 0.160).
CONCLUSIONS: ASCT was associated with the most durable survival among consolidation strategies after R-MVP induction. These findings, derived from a large real-world, multi-institutional cohort, support ASCT as the preferred consolidation for eligible patients while underscoring the heterogeneity of current practice and the need for prospective validation.

Keywords:  autologous stem cell transplantation; consolidation; methotrexate; primary central nervous system lymphoma; procarbazine; radiation therapy; rituximab; vincristine

DOI:  https://doi.org/10.1002/cam4.71806
Ann Pathol. 2026 Apr 15. pii: S0242-6498(26)00063-5. [Epub ahead of print]

[Blastoïd mantle cell lymphoma, TdT-positive: Toward a more juvenile profile?]

Radu Pirlog, Justine Cohen, Cyrielle Robe, Baptiste Gillet, Josette Briere, Emmanuele Lechapt, Philippe Gaulard, Elsa Poullot.

  Mantle cell lymphoma is a B-cell lymphoma that occurs predominantly in individuals over 65 years of age and accounts for approximately 2-10% of all B-cell lymphomas. Two forms of the disease are recognized: the classical nodal mantle cell lymphoma and the non-nodal form, the later being often leukemic and SOX11-, with differences at the clinical, immunohistochemical, and molecular levels. The main validated prognostic factors in mantle cell lymphoma include morphology, the Ki-67 proliferation index, and presence of TP53 mutations and/or immunohistochemical expression of the p53 protein. Clinically, the prognosis of patients with mantle cell lymphoma has markedly improved with the introduction of Bruton's tyrosine kinase inhibitors (BTKi), anti-CD20 monoclonal antibodies, and immunotherapies. We report a 63 year-old man with bone marrow involvement by mantle cell lymphoma displaying an immunohistochemical profile CD20+, CD5+, cyclin D1+, SOX11-, with distinctive features including blastoid morphology, diffuse TdT expression, and MYC gene rearrangement. This exceptional association of blastoid morphology, TdT expression, and MYC rearrangement in mantle cell lymphoma suggests a process of tumor dedifferentiation and broadens the clinico-biological spectrum of mantle cell lymphoma, raising significant diagnostic and prognostic challenges.

Keywords:  Blastoid morphology; Lymphome du manteau; MYC translocation; Mantle cell lymphoma; Morphologie blastoïde; Réarrangement MYC; TDT

DOI:  https://doi.org/10.1016/j.annpat.2026.03.006
Blood Cancer Discov. 2026 Apr 17.

A Phase 2, Open-Label, Multicenter Study of the Safety and Efficacy of TAK-007 in Adult Patients with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma.

Justin M Darrah, Indumathy Varadarajan, Amitkumar Mehta, Jennifer N Saultz, Matthew S McKinney, Monalisa Ghosh, Usama Gergis, Andrew Krueger, Kevin J Galinsky, Girish Bende, Ajeetha Ramachandran, Varsha Sundaresan, Siddha Kasar, Bradley Hupf, Sharon Chen, Leopold Sellner, Reem Karmali.

In relapsed/refractory large B-cell lymphoma (LBCL), chimeric antigen receptor (CAR)-natural killer (NK) cell therapies offer potential advantages over CAR-T-cell therapies, including off-the-shelf availability and scalable manufacturing. We performed a phase 2 study of single-dose TAK-007, a cryopreserved, cord blood-derived, off-the-shelf CD19 CAR-NK cell therapy, in 26 heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Adverse events were manageable, with limited grade 1-2 cytokine release syndrome (11.5%). Overall response rate with TAK-007 800 x106 CD19 CAR+ viable NK cells (n=14) was 60.9% (95% CI: 38.5-80.3). Median progression-free survival was 2.0 months (95% CI: 0.99-3.58) in LBCL (n=10) and 5.6 months (95% CI: 1.05-8.57) in indolent NHL (n=7) expansion cohorts. Deep molecular responses, including ctDNA-negative responses, were achieved. Not all TAK-007 products elicited clinical responses; single cell RNA-sequencing showed NK proliferating and NK-CD56dim cell enrichment in TAK-007 products eliciting/not eliciting responses, respectively, which could inform product selection.

DOI: https://doi.org/10.1158/2643-3230.BCD-25-0323-A