bims-hemali 2025-05-18 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2025–05–18
27 papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Daratumumab for newly diagnosed multiple myeloma: Pooled analysis of patients aged ≥65 years from GRIFFIN and PERSEUS.
Adult Acute Lymphoblastic Leukemia: 2025 Update on Diagnosis, Therapy, and Monitoring.
Sustained MRD negativity drives maintenance stop.
Polatuzumab Vedotin, zanubrutinib and rituximab (Pola-ZR) achieved rapid and deep response in untreated frail and elderly DLBCL.
How I Evaluate and Treat Resistance and Relapse in CML.
A phase 2 Trial of CHOP with Anti-CCR4 Antibody Mogamulizumab for older Patients with Adult T-Cell Leukemia/Lymphoma.
Optimal Depth of the Treatment Response Before Allogeneic Hematopoietic Transplantation for Chronic Myeloid Leukemia in Chronic Phase.
Improved efficacy of concurrent anti-PD1 antibody plus AVD versus ABVD in patients with newly diagnosed early unfavorable and advanced stage classic Hodgkin lymphoma: a retrospective matched cohort study.
[Novel treatment strategies for polycythemia vera: focus on ropeginterferon alfa-2b].
Right time: stopping multiple myeloma maintenance.
Treatment of Older Patients With ALL.
Clinical benefit of tafasitamab plus lenalidomide in relapsed or refractory diffuse large Bcell lymphoma: real-world data from the EarlyMIND study.
Prevention is better than cure.
How I approach hematopoietic stem cell transplantation for CML in a TKI world.
Conflating polycythemia vera with essential thrombocytosis.
Efficacy and safety of azacitidine for VEXAS syndrome: a large-scale retrospective study from the FRENVEX group.
Prognostic Value of Post-Transplant MRD Negativity in Standard Versus High- and Ultra-High-Risk Multiple Myeloma Patients.
Efficacy and safety of selinexor-based regimens as first-line treatments for elderly patients with diffuse large B-cell lymphoma: a real-world study.
Uncommon phenotypes of BCR::ABL1-positive chronic myelogenous leukemia: a review.
Efficacy of Axicabtagene Ciloleucel Compared to Historical Treatments for Relapsed/Refractory Diffuse Large B-Cell Lymphoma of Asian Descent: A Matching Adjusted Indirect Comparison of ZUMA-1 vs REAL-TREND.
Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells.
Long-Term Transfusion Independence with Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent-Naive, Lower-Risk Myelodysplastic Syndromes in the COMMANDS Trial.
Management of common autoimmune diseases in patients with myeloproliferative neoplasms treated with pegylated interferon alfa-case report, review of the literature and multidisciplinary clinical practice recommendations.
Optimizing therapy for relapsed/refractory classic Hodgkin lymphoma in the era of PD-1 blockade.
Real-World Treatment Outcomes of Different Sequencing Options with Daratumumab, Lenalidomide, and Dexamethasone in Patients with Transplant-Ineligible Multiple Myeloma in Japan.
Dasatinib Pharmacokinetics and Advanced Nanocarrier Strategies: from Systemic Limitations to Targeted Success.
Has the time for treatment-free remission in Philadelphia chromosome-positive acute lymphoblastic leukemia arrived?

Clin Lymphoma Myeloma Leuk. 2025 Apr 11. pii: S2152-2650(25)00139-9. [Epub ahead of print]

Daratumumab for newly diagnosed multiple myeloma: Pooled analysis of patients aged ≥65 years from GRIFFIN and PERSEUS.

Paula Rodriguez-Otero, Peter M Voorhees, Mario Boccadoro, Jacob Laubach, Hermann Einsele, Douglas W Sborov, Meletios A Dimopoulos, Annemiek Broijl, Roberto Mina, Andrew Spencer, Fredrik Schjesvold, Rebecca Silbermann, Francesca Gay, Luciano J Costa, Aurore Perrot, Yanfang Liu, Jianping Wang, Anna Sitthi-Amorn, Robin Carson, Annelore Cortoos, Saad Z Usmani, Paul G Richardson, Philippe Moreau, Pieter Sonneveld, Jonathan L Kaufman.

   BACKGROUND: Older adults with newly diagnosed multiple myeloma (NDMM) have poor prognosis and constitute a subgroup of particular interest. In the GRIFFIN (NCT02874742) and PERSEUS (NCT03710603) studies, adding daratumumab to bortezomib/lenalidomide/dexamethasone (VRd) induction/consolidation and lenalidomide (R) maintenance deepened responses and improved progression-free survival (PFS) versus VRd/R in transplant-eligible patients with NDMM. Subgroup analyses of patients aged ≥65 years in PERSEUS demonstrated less pronounced PFS benefits (HRs: 0.97 [computerized algorithm]; 0.87 [independent review committee (IRC)]), potentially due to small event numbers, cytogenetic risk imbalances (high risk: D-VRd, 25.5%; VRd, 19.5%), and specific censoring rules. Here, we report results from a post hoc, pooled analysis of GRIFFIN and PERSEUS in patients aged ≥65 years (D-VRd, n = 122; VRd, n = 115).
METHODS: Using patient-level data, PFS analysis was evaluated per computerized algorithm in GRIFFIN and IRC in PERSEUS, stratified by International Staging System stage and cytogenetic risk, with no censoring of PFS events after ≥2 missing disease evaluations.
RESULTS: At a median follow-up of 49.6/47.5 months (GRIFFIN/PERSEUS), a trend in improved PFS was seen among patients aged ≥65 years favoring D-VRd (HR, 0.56 [95% CI, 0.30-1.01]). D-VRd improved rates of complete response or better (82.8% vs. 67.0%; OR, 2.37 [95% CI, 1.28-4.39]; P = .0046) and minimal residual disease negativity (10-5; 66.4% vs. 41.7%; OR, 2.75 [95% CI, 1.61-4.71]; P = .0002) versus VRd. No new safety concerns were identified.
CONCLUSION: These data support use of D-VRd followed by D-R maintenance as standard of care for all transplant-eligible patients with NDMM, regardless of age up to 70 years.

Keywords:  Minimal residual disease; Older adults; Progression-free survival; Safety; Transplantation

DOI:  https://doi.org/10.1016/j.clml.2025.04.007
Am J Hematol. 2025 May 16.

Adult Acute Lymphoblastic Leukemia: 2025 Update on Diagnosis, Therapy, and Monitoring.

Hagop Kantarjian, Elias Jabbour.

   DISEASE OVERVIEW: Acute lymphoblastic leukemia (ALL) is a disease of lymphoid progenitor cells arising in the bone marrow and extramedullary sites. While it is the most common pediatric cancer, ALL is a rare disease overall, with approximately 6500 new cases diagnosed in the United States, in 2024. Current treatment relies on multiagent chemotherapy administered over 2-3 years, resulting in long-term survival in 80%-90% in pediatric patients compared to 40%-50% in adult patients, depending upon patient- and disease-specific characteristics.
PHILADELPHIA CHROMOSOME-POSITIVE B-CELL ALL: Historically considered a poor risk ALL subtype, the treatment and outcome of Philadelphia chromosome (Ph)-positive B-cell ALL were drastically changed with the advent of the BCR::ABL1 tyrosine kinase inhibitors (TKIs). The combination of a TKI with a backbone of multiagent chemotherapy, or more recently blinatumomab, is the mainstay of therapy, resulting in 5-year survival rates of 80+%. Achieving a complete molecular remission, particularly by next generation sequencing, is an important prognostic indicator, which may identify patients who may avoid allogeneic stem cell transplantation (SCT).
PHILADELPHIA CHROMOSOME-NEGATIVE B-CELL ALL: The treatment approach for patients with Ph-negative B-cell ALL was historically composed of a chemotherapy backbone (either pediatric-inspired, or Hyper-CVAD based). Novel agents including inotuzumab ozogamicin and blinatumomab are being incorporated into these regimens to improve the rates of measurable residual disease negativity and long-term outcomes. While differences in long-term survival rates differ between age groups, such as adolescents and young adults compared to older adults (≥ 60 years), with these immunotherapy-chemotherapy regimens, the 4-year survival rates have improved to 80%-85% among patients who are able to receive these treatments. Elderly patients represent a difficult population to treat due to poor chemotherapy tolerance, high-risk disease features, and increased risk of developing therapy-related myeloid neoplasms. The use of inotuzumab ozogamicin and blinatumomab in lieu of intensive chemotherapy in this population has improved safety and efficacy in patients ≥ 60 years old. Clinical trials incorporating chimeric antigen receptor (CAR) T-cell therapy into treatment for older patients are in progress.
T-CELL ALL: Combination chemotherapy regimens incorporating pegylated asparaginase and nelarabine are the standard for patients with T-cell ALL. Early T-cell precursor (ETP) ALL is a high-risk subgroup for which allogeneic SCT should be considered. Inclusion of the BCL-2 inhibitor venetoclax into treatment for patients with ETP-ALL may be beneficial and is currently being investigated.
SALVAGE THERAPY: Several therapies are approved as single agents in the salvage setting. However, the best outcomes are obtained with combination therapy including chemo- and immuno- therapies followed by CAR T-cell consolidation and allogeneic SCT. Clinical trials optimizing this approach are ongoing.

Keywords:  acute lymphoblastic leukemia; management; outcome

DOI:  https://doi.org/10.1002/ajh.27708
Blood. 2025 May 15. 145(20): 2397

Sustained MRD negativity drives maintenance stop.

DOI: https://doi.org/10.1182/blood.2025029434
Ann Hematol. 2025 May 16.

Polatuzumab Vedotin, zanubrutinib and rituximab (Pola-ZR) achieved rapid and deep response in untreated frail and elderly DLBCL.

Yuhong Ren, Hui Tan, Jingli Zhuang, Luya Cheng, Ling Yuan, Lili Ji, Yang Ke, Xuejiao Zhang, Zhixiang Cheng, Jing Li, Peng Liu.

  First-line treatment balancing efficacy and safety is urgently needed for frail and elderly diffuse large B-cell lymphoma (DLBCL) patients. We designed a triplet chemo-light regimen, Pola-ZR, in previously untreated frail and elderly DLBCL patients to assess the efficacy and safety in a prospective DLBCL cohort (NCT06203652). Polatuzumab vedotin was given 1.8 mg/KG intravenously on day 1, zanubrutinib 160 mg twice a day orally from day 1 to day 21, and rituximab 375 mg/m2 intravenously on day 1. Twenty-one days were a cycle. If assessed complete response (CR) after 6 cycles, patients would receive zanubrutinib alone for another 6 cycles. PET/CT or contrast-enhanced CT scan was scheduled every 3 cycles. The primary end point was overall response rate (ORR) after 6 cycles. Twenty-four patients were enrolled from 01 Apr 2023 to 20 Dec 2023. Median age was 73. Sixteen (66.7%) patients had an international prognostic index score of 3 to 5. After a median follow-up of 10.2 months, the CR rate and ORR after 6 cycles was 83% and 83%. Non-responders had high total metabolic tumour volume. Lung infection was the major safety concern. PJP prophylaxis was recommended. Pola-ZR regimen showed rapid and deep response with manageable safety profiles in both GCB and non-GCB subtypes.

Keywords:  Diffuse large B-cell lymphoma; Elderly; Polatuzumab vedotin; Response; Zanubrutinib

DOI:  https://doi.org/10.1007/s00277-025-06412-z
Blood. 2025 May 15. pii: blood.2024026511. [Epub ahead of print]

How I Evaluate and Treat Resistance and Relapse in CML.

Simona Soverini, Fausto Castagnetti.

As evidenced by the excellent survival outcomes, chronic myeloid leukemia (CML) treatment in the era of tyrosine kinase inhibitors (TKIs) is often successful. However, when response milestones are not met or lost, treatment decision-making may be challenging. The availability for first-, second- or subsequent-line use of six different TKIs, each with definite and often non-overlapping features in terms of mechanism of action, potency, activity against resistance mutations and tolerability profile provides a reassuring opportunity to rescue an optimal response, but it must be exploited carefully to avoid hasty or inappropriate choices. When and how to sequence TKIs, and if and when to consider transplant are very important issues. 'One for all' rules cannot be formulated, since for each individual patient the decision process requires investigation and integration of a series of clinical and biological factors. After discussing how resistance is defined, we here aim to provide practical guidance to therapeutic reassessment, discussing which laboratory investigations should be performed, how they should be interpreted, which additional clinical considerations are mandatory, and how these factors should be weighed and reasonably concur to the final decision.

DOI: https://doi.org/10.1182/blood.2024026511
Blood. 2025 May 15. pii: blood.2024027902. [Epub ahead of print]

A phase 2 Trial of CHOP with Anti-CCR4 Antibody Mogamulizumab for older Patients with Adult T-Cell Leukemia/Lymphoma.

Makoto Yoshimitsu, Ilseung Choi, Shigeru Kusumoto, Mototsugu Shimokawa, Atae Utsunomiya, Youko Suehiro, Tomonori Hidaka, Kisato Nosaka, Hidenori Sasaki, Shinya Rai, Shinobu Tamura, Satsuki Owatari, Ki-Ryang Koh, Daisuke Nakamura, Masahito Tokunaga, Masaaki Sekine, Yuma Sakamoto, Hiroshi Inagaki, Takashi Ishida, Kenji Ishitsuka.

No standard of care for elderly patients with aggressive adult T-cell leukemia/lymphoma (ATL) has been established. We evaluated the efficacy of CHOP every 2 weeks with mogamulizumab (Moga) (Moga-CHOP-14) for untreated elderly patients with ATL. In this multicenter phase 2 trial, patients aged ≥66 years and those aged 56-65 years ineligible for transplantation received 6 cycles of Moga-CHOP-14, followed by 2 cycles of Moga monotherapy. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints were the complete response (CR) rate, overall response rate (ORR), overall survival (OS), 1-year event-free survival (EFS), and safety. We also investigated the impact of CCR4 mutation and Moga-associated cutaneous adverse events (cAEs) on PFS and OS. The study protocol was amended to allow the dosing interval to be extended to 21 days at the physician's discretion. Among 48 evaluable patients, the 1-year PFS was 36.2% (90% confidence interval [CI], 24.9-47.6), with a median follow-up of 1.6 years. One-year OS and EFS were 66.0% (95% CI, 50.6-77.6) and 29.9% (95% CI, 17.6-43.2), respectively. CR and ORR were 64.6% (95%CI, 49.5-77.8) and 91.7% (95% CI, 80.0-97.7). No unexpected toxicities were observed. Of the 47 patients who received ≥2 cycles of CHOP, 20 (42.6%) received CHOP-14, among whom 12 (25.5%) completed 6 cycles. CCR4 mutation and Moga-associated cAE were associated with better OS. This study showed that Moga-CHOP significantly improved PFS, though the optimal interval for CHOP remains undetermined. Moga-CHOP is now considered a preferable first-line treatment for these patients. Clinical Trial Identifier: jRCTs041180130.

DOI: https://doi.org/10.1182/blood.2024027902
Am J Hematol. 2025 May 12.

Optimal Depth of the Treatment Response Before Allogeneic Hematopoietic Transplantation for Chronic Myeloid Leukemia in Chronic Phase.

Yosuke Okada, Takeshi Kondo, Takuya Miyazaki, Yutaka Shimazu, Yosuke Minami, Fumihiko Ouchi, Shinichi Kako, Masatsugu Tanaka, Tetsuya Nishida, Shin-Ichiro Fujiwara, Naoyuki Uchida, Hirohisa Nakamae, Yuta Hasegawa, Keisuke Kataoka, Shingo Yano, Mamiko Sakata-Yanagimoto, Ayumu Ito, Jun Ishikawa, Yoshinobu Kanda, Koji Kawamura, Takahiro Fukuda, Yoshiko Atsuta, Takayoshi Tachibana.



Keywords:  CML; depth of the treatment response; stem cell transplantation

DOI:  https://doi.org/10.1002/ajh.27706
Cancer Immunol Immunother. 2025 May 15. 74(7): 206

Improved efficacy of concurrent anti-PD1 antibody plus AVD versus ABVD in patients with newly diagnosed early unfavorable and advanced stage classic Hodgkin lymphoma: a retrospective matched cohort study.

Mengqiu Wu, Peng Sun, Baitian Zhao, Hang Yang, Yi Xia, Man Nie, Qingqing Cai, Huiqiang Huang, He Huang, Zhongjun Xia, Yu Wang, Zhiming Li, Panpan Liu.

   BACKGROUND: The prognosis of early unfavorable and advanced stage classic Hodgkin lymphoma (cHL) remains suboptimal with the widely used ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) regimen. Novel agents such as brentuximab vedotin (BV) and anti-PD-1 antibody have demonstrated high efficacy and good tolerance in relapsed/refractory cHL and have also shown promising results in the frontline setting. However, concurrent administration of anti-PD-1 antibody plus AVD in comparison with traditional ABVD regimen alone in untreated classic Hodgkin lymphoma (cHL) has yet to be adequately studied in real-world clinical practice.
METHODS: We enrolled eligible adult patients with histologically confirmed cHL who had received initial treatment with the ABVD regimen, or the novel combination regimens of anti-PD1-AVD. The study endpoints included modified progression-free survival (mPFS) and complete response (CR) after 2 cycles of therapy. Propensity score matching (PSM) was performed to balance clinical variables between regimens prior to efficacy comparisons.
RESULTS: Of 172 patients, 137 received the ABVD regimen and 35 received the anti-PD1-AVD regimen. With a median follow-up of 37.7 months, significantly prolonged 3-year modified PFS was reported for anti-PD1-AVD versus ABVD (PSM: 91.0 vs. 61.6%, p = 0.032). Significantly improved CR rate was observed with anti-PD1-AVD versus ABVD (PSM: 86.7 vs. 63.8%, p = 0.049).
CONCLUSIONS: In this real-world study, concurrent anti-PD1 antibody with AVD showed significantly prolonged modified PFS and improved CR rate after cycle 2 versus ABVD regimen, supporting the use of novel agents in frontline therapy.

Keywords:  Chemotherapy; Complete response; Immune checkpoint inhibitor; Lymphoma; Modified progression-free survival

DOI:  https://doi.org/10.1007/s00262-025-04041-z
Rinsho Ketsueki. 2025 ;66(4): 258-266

[Novel treatment strategies for polycythemia vera: focus on ropeginterferon alfa-2b].

Keita Kirito.

  The current main treatment goal of polycythemia vera (PV) is preventing thromboembolic and hemorrhagic complications. However, these therapeutic strategies cannot delay progression of PV. Therefore, there is an unmet need for next-generation therapeutic strategies to slow disease progression and improve survival in patients with PV. One of the most promising agents for modifying the disease course of myeloproliferative neoplasms is interferon alpha, which has been used to treat PV since the 1980s. Notably, it achieved cytogenetic or molecular responses in some patients. However, conventional interferon was not widely used due to its high incidence of adverse events and poor tolerance. Ropeginterferon alfa-2b (ropeg) is a unique, site-selective polyethylene glycol-conjugated form of recombinant interferon alpha. A phase 1/2 study of ropeg for PV patients showed low toxicity and improved tolerability, along with significant molecular response. A phase 3 randomized study (PROUD-PV/CONTINUATION-PV) revealed that treatment with ropeg continuously decreased the JAK2V617F allele burden compared to hydroxyurea and improved event-free survival (with events defined as thromboembolic events, disease progression, or death). A phase 2 study in Japanese patients with PV further confirmed the efficacy of ropeg.

Keywords:  JAK2V617F; Molecular response; Polycythemia vera; Ropeginterferon alfa-2b

DOI:  https://doi.org/10.11406/rinketsu.66.258
Blood. 2025 May 15. 145(20): 2241-2242

Right time: stopping multiple myeloma maintenance.

Philip McCarthy, Hemn Mohammadpour.

DOI: https://doi.org/10.1182/blood.2025028814
Am Soc Clin Oncol Educ Book. 2025 Jun;45(3): e473298

Treatment of Older Patients With ALL.

Elias Jabbour, Fadi G Haddad, Hagop Kantarjian.

Older patients with ALL often have high-risk disease characterized by adverse-risk cytogenetic and molecular abnormalities, as well as Philadelphia chromosome (Ph)-positive and Ph-like phenotypes. They often have comorbidities resulting in poor tolerance to chemotherapy and are at risk of developing therapy-related myeloid neoplasms (t-MNs). In Ph-negative ALL, the duration and intensity of chemotherapy was reduced, and outcomes improved with the addition of inotuzumab ozogamicin (InO) and blinatumomab into the frontline setting. However, t-MNs are still being observed, prompting the development of chemotherapy-free regimens with InO and blinatumomab as well as chimeric antigen receptor (CAR) T-cell therapies in high-risk disease. In Ph-positive ALL, chemotherapy and allogeneic hematopoietic stem-cell transplantation (HSCT) were historically considered a standard of care. However, the introduction of blinatumomab and newer-generation BCR::ABL1 tyrosine kinase inhibitors (TKIs) into the frontline setting significantly improved outcomes. The combination of blinatumomab and ponatinib induced high rates of complete molecular responses and excellent survival, without reliance on HSCT. A subset of patients with elevated WBC count at diagnosis are at particular risk of CNS and systemic relapse and may require additional strategies such as incorporating one to two cycles of high-dose methotrexate/cytarabine into consolidation, and potentially CAR T cells. In T-cell ALL, adding venetoclax into the frontline setting has improved outcomes. In early T-cell precursor ALL, HSCT is still needed. To further improve outcomes in older patients, novel agents such as subcutaneous blinatumomab, CAR T cells, newer-generation TKIs, and menin inhibitors should be investigated in the frontline setting.

DOI: https://doi.org/10.1200/EDBK-25-473298
Haematologica. 2025 May 15.

Clinical benefit of tafasitamab plus lenalidomide in relapsed or refractory diffuse large Bcell lymphoma: real-world data from the EarlyMIND study.

Gabriel Brisou, Jérôme Paillassa, Sophie Bernard, Olivier Tournilhac, Luc-Matthieu Fornecker, Frédéric Maloisel, Lauris Gastaud, Eric Durot, Adrian Tempescul, Thorsten Braun, Vadim Ivanov, Brieuc Cherel, Caroline Serrier, Jeremy Delage, Abderrazak El Yamani, Baptiste Delapierre, Laure Lebras, Elsa Lestang, Camille Villesuzanne, Philippe Agape, Guillaume Escure, Ludovic Fouillet, Christophe Nicol, Gaëlle Olivier, Anthony Levy, Anne-Sophie Le Bris, Ophélie Cassuto, Laura Jacquemelle, Corinne Haioun, Charles Herbaux.

Tafasitamab combined with lenalidomide was approved in Europe in 2021 for transplant-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma. Approval was based on the L-MIND study, which demonstrated a 57.5% overall response rate (ORR), 41.3% complete response (CR) rate, 12.1 months median progression-free survival (PFS), and 33.5 months median overall survival (OS) at five years. The multicenter retrospective EarlyMIND study analyzed real-world efficacy and treatment patterns of patients receiving tafasitamab plus lenalidomide for second (2L cohort) to fourth (3L + 4L cohort) line in the French Early Access Program. Outcomes were analyzed overall and according to number of previous lines. Post hoc analyses were conducted on subgroups based on prognostic factors, performance status, primary refractoriness, cell of origin, and treatment response. Overall, 186 patients were included (2L: n=105; 3L + 4L: n=81). Median age was 78 years; most patients had early relapsed disease (71.2%), including 60.2% with primary refractory disease. At median follow-up of 8.2 months, best ORR was 46.8%, with CR rate of 29%. ORR was greater in 2L (50.5%) versus 3L + 4L (42%). Median PFS and OS were 4.7 and 10 months, respectively in the overall population, 5.4 and 10.6 months in 2L, and 3.6 and 8.2 months in 3L + 4L. Long-lasting responses were observed in patients achieving CR, with median duration of response, PFS, and OS not reached. Median time to CR as best OR was four cycles, regardless of treatment line. Despite involving a frail population with high-risk disease characteristics, results of this large real-world European retrospective study on tafasitamab plus lenalidomide are encouraging, with almost one third of patients experiencing long-lasting CR.

DOI: https://doi.org/10.3324/haematol.2024.287141
Blood. 2025 May 15. 145(20): 2236-2237

Prevention is better than cure.

Olaf Penack.

DOI: https://doi.org/10.1182/blood.2025029023
Blood. 2025 May 12. pii: blood.2024026512. [Epub ahead of print]

How I approach hematopoietic stem cell transplantation for CML in a TKI world.

Yves Chalandon, Federico Simonetta, Stavroula Masouridi-Levrat.

Following the introduction of tyrosine kinase inhibitors (TKI), the number of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic phase chronic myeloid leukemia (CP-CML) has dramatically decreased. Imatinib was the 1st TKI introduced into the clinical arena, predominantly utilized in the 1st line setting. In cases of insufficient response, resistance, or intolerance, CML patients can subsequently be treated with a 2nd, 3rdor 4th generation TKI. However, despite the approval of 1st, 2nd, 3rd, 4th generation TKI allo-HSCT still remains indicated for a minority of CML patients. Here, we discuss the indications in the era of TKI through different cases representing the clinical situations for which allo-HSCT remains the best option. We also propose our transplant strategy to decrease transplant-related morbidity, particularly graft-versus-host disease (GvHD), and mortality in the particular context of CML, a disease that is one of the most sensitive to immune cellular therapy, allowing the use of a combination of donor lymphocyte infusion (DLI) and TKI for post-transplant molecular progression.

DOI: https://doi.org/10.1182/blood.2024026512
Blood Adv. 2025 May 09. pii: bloodadvances.2025016843. [Epub ahead of print]

Conflating polycythemia vera with essential thrombocytosis.

Jerry L Spivak.

DOI: https://doi.org/10.1182/bloodadvances.2025016843
Blood. 2025 May 15. pii: blood.2024028133. [Epub ahead of print]

Efficacy and safety of azacitidine for VEXAS syndrome: a large-scale retrospective study from the FRENVEX group.

Vincent Jachiet, Olivier Kosmider, Maxime Beydon, Jerome Hadjadj, Lin-Pierre Zhao, Vincent Grobost, Valentin Lacombe, Guillaume Le Guenno, Yann Nguyen, Jean Benoit Arlet, Jeremie Dion, Mael Heiblig, Alice Garnier, Maxime Samson, Achille Aouba, Sylvain Thepot, Sophie Dimicoli-Salazar, Fabien Dutasta, Benoit Faucher, Estibaliz Lazaro, Veronique Morel, Antoine Neel, Roderau Outh, Holy Bezanahary, Julien Rossignol, Anne-Sophie Alary, Audrey Bidet, Pauline Blateau, Anne Bouvier, Guilaine Boursier, Matthieu Decamp, Benjamin Lebecque, Yannick Le Bris, Pierre Sujobert, Alice Marceau-Renaut, Cedric Pastoret, David Rizzo, Nathalie Boiret-Dupré, Lara Boucher, Stéphanie Dulucq, Franck Genevieve, Cassandra Jadeau, Pierre Lemaire, Romain Vazquez, Jean Baptiste Rieu, Olivier Fain, Sophie Anne Georgin-Lavialle, Lucie Rigolot, Lise Larcher, Pierre Hirsch, Benjamin Terrier, Pierre Fenaux, Arsène M Mékinian, Thibault Comont.

VEXAS (Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic) syndrome is a severe monogenic disorder caused by somatic UBA1 mutations, characterized by inflammation, cytopenias and frequent association with myelodysplastic neoplasms (MDS). Steroid dependence is common, and targeted therapies have demonstrated limited efficacy. Azacitidine (AZA), a hypomethylating agent used in MDS, has shown potential in VEXAS but data remain limited. This multicenter retrospective study assessed AZA efficacy and safety in 88 genetically confirmed VEXAS patients from the FRENVEX (French VEXAS) group, 80% meeting WHO 2022 MDS criteria. Inflammatory response rates were 41% at 6 months and 54% at 12 months, regardless of MDS status. A total of 50 (61%) patients achieved inflammatory response, with 70% occurring at 6 months, suggesting a delayed median response. Among responders, relapse-free survival on AZA was 90% at 1 year and 85% at 5 years. Of the 12 responders who discontinued AZA, 9 relapsed after a median of 3.1 years (range: 0.4-5.6), with effective re-exposure in 4 of 5 patients. Hematological responses included red blood cell transfusion independence in 65% and platelet improvement in 77% of patients. Molecular response, defined as a ≥25% reduction in UBA1 variant allele frequency (VAF), was observed in 65% of patients, all of whom achieved inflammatory and hematological responses; and VAF dropped below 2% in 43% of cases. Infections (34%) and cytopenias (36%) were common, particularly during the first three cycles. This study establishes AZA as an effective therapy for VEXAS, improving inflammation, cytopenias, and UBA1 clonal burden, warranting larger prospective trials.

DOI: https://doi.org/10.1182/blood.2024028133
Cancers (Basel). 2025 May 04. pii: 1565. [Epub ahead of print]17(9):

Prognostic Value of Post-Transplant MRD Negativity in Standard Versus High- and Ultra-High-Risk Multiple Myeloma Patients.

Lea Jasmin Kündgen, Dilara Akhoundova, Michele Hoffmann, Myriam Legros, Inna Shaforostova, Katja Seipel, Ulrike Bacher, Thomas Pabst.

  Background: Cytogenetic abnormalities and the persistence of minimal residual disease (MRD) following autologous stem cell transplantation (ASCT) are two established prognostically unfavorable biomarkers in multiple myeloma (MM). Previous studies have shown that post-transplant MRD status is a powerful predictor of progression-free survival (PFS) and overall survival (OS). However, the impact of MRD remains poorly characterized in MM patients with high- or ultra-high-risk cytogenetics. Objectives: This study investigated the prognostic value of post-transplant MRD in standard- versus high- and ultra-high-risk MM. To this aim, we performed a retrospective analysis of 137 MM patients who underwent high-dose chemotherapy (HDCT) and ASCT at our institution between January 2019 and December 2021. Cytogenetics were assessed by fluorescence in situ hybridization. High-risk genomic alterations included del(17p), t(4;14), t(14;16), t(14;20), gain(1q), and TP53 mutations, with two or more alterations defining the ultra-high-risk category. MRD was assessed in bone marrow aspirates post-ASCT using flow cytometry. Results: Eighty-two (60%) patients were categorized as being at standard risk, forty (29%) as high risk, and fifteen (11%) as ultra-high risk. Median follow-up was 47 months. MRD negativity was achieved in 76 (55%) patients. At 48 months, the overall PFS rate was 61% (72%, 50%, and 32% for the standard-, high-, and ultra-high-risk subgroups, respectively; p = 0.0004), while the OS rate was 85% (89%, 79%, and 80% in standard-, high-, and ultra-high-risk MM patients, respectively; p = 0.1494). Within the standard-risk subgroup, longer PFS was observed for patients achieving MRD negativity (p = 0.0172). High- and ultra-high-risk patients showed no significant differences in PFS when stratified by MRD status, possibly due to prompt progression to MRD positivity. Conclusions: Our results suggest that high- and ultra-high-risk MM patients might benefit from closer response monitoring, including dynamic MRD assessment. Further, high- and ultra-high-risk patients might require a more intensive peri-transplant treatment.

Keywords:  autologous stem cell transplantation; cytogenetics; high risk; minimal residual disease; multiple myeloma; overall survival; progression-free survival; ultra-high risk

DOI:  https://doi.org/10.3390/cancers17091565
BMC Cancer. 2025 May 15. 25(1): 878

Efficacy and safety of selinexor-based regimens as first-line treatments for elderly patients with diffuse large B-cell lymphoma: a real-world study.

Jing Li, Jingjing Ge, Tingting Chen, Jianghua Cao, Xiaohua He, Shulan Wang, Hang Yang, Yu Wang, Peng Sun, Jiajia Huang, Shan Liu, Zhiming Li.

   PURPOSE: This study aimed to evaluate the efficacy and safety of selinexor-based regimens as first-line treatments for elderly patients with diffuse large B-cell lymphoma (DLBCL).
METHODS: A retrospective analysis of 16 elderly patients with DLBCL who received selinexor-based regimens as first-line treatments at Sun Yat-sen University Cancer Center from November 2021 to September 2023 was conducted. The primary endpoint was the objective response rate (ORR), while the secondary endpoints included progression-free survival (PFS), duration of response (DOR), and safety.
RESULTS: Among the 16 elderly patients, 7 were male (43.8%), and 9 were female (56.2%). The median age was 70.5 years (range, 60-80). The ORR was 93.8%, and 13 patients (81.3%) achieved a complete response (CR), 2 patients (12.5%) achieved a partial response (PR) and 1 patient had progressive disease (PD). It is noteworthy that all 5 patients who received chemotherapy-free regimens achieved CR. The median follow-up was 8.5 months (range, 2.7-22.9). The median PFS was not reached, and the 1-year PFS rate was 79.6%. A total of 81.3% of the patients maintained a response for at least 6 months, and 25% maintained a response for at least 12 months. All 3 patients aged ≥ 75 years achieved CR (100%). Haematologic AEs, including leukopenia (n = 15, 93.8%), neutropenia (n = 13, 81.3%), anaemia (n = 8, 50.0%) and thrombocytopenia (n = 4, 25.0%), were common. The most common nonhaematologic AEs were nausea and vomiting (n = 6, 37.5%), fatigue (n = 5, 31.3%) and decreased appetite (n = 5, 31.3%), most of which were limited in severity to grades 1 or 2 and improved with standard supportive care.
CONCLUSIONS: In the real world, selinexor-based regimens demonstrate good efficacy and controllable safety as first-line treatments for elderly patients with DLBCL.

Keywords:  Diffuse large B-cell lymphoma; Efficacy; Elderly patients; Safety; Selinexor

DOI:  https://doi.org/10.1186/s12885-025-14295-6
Haematologica. 2025 May 15.

Uncommon phenotypes of BCR::ABL1-positive chronic myelogenous leukemia: a review.

Audrey N Jajosky, Marshall A Lichtman.

BCR::ABL1-positive chronic myelogenous leukemia (CML) presents with a typical phenotype in over 95 percent of cases. These are associated with a p210kDa oncoprotein (M-bcr genotype). In these cases, the consideration of CML is high on the differential diagnosis list and appropriate genetic studies to confirm the BCR::ABL1 oncogene are de rigueur. The elevated white cell count, dominant granulocytes, myeloid immaturity and the absent to low blast concentration in the blood, the mild anemia, the normal platelet count or mild thrombocytosis and the frequency of basophilia usually point to the tentative diagnosis of CML or CML is included in the differential diagnosis without ambiguity. In a very small fraction of cases, the diagnosis of BCR::ABL1-positive CML is less evident. These syndromes include (i) BCR::ABL1-positive thrombocythemia, (ii) so-called neutrophilic BCR::ABL1-positive CML and (iii) the m-bcr (p190BCR-ABL1) variant of CML, often with an absolute and relative monocytosis. In these uncommon forms, there are often misleading blood cell counts. An interesting biological feature is the striking predominance of females in these three atypical presentations. In the fourth variant, (iv) eosinophilic predominant CML, the five reported cases have all been in males. We also consider the very rare phenomenon of (v) smoldering CML (syn. pre-CML or aleukemic CML), which also has a female predominance. The misdiagnosis or delayed diagnosis of these atypical syndromes is consequential because of the beneficial response to tyrosine kinase inhibitors (TKIs) in these patients.

DOI: https://doi.org/10.3324/haematol.2025.287792
Hematol Oncol. 2025 May;43(3): e70100

Efficacy of Axicabtagene Ciloleucel Compared to Historical Treatments for Relapsed/Refractory Diffuse Large B-Cell Lymphoma of Asian Descent: A Matching Adjusted Indirect Comparison of ZUMA-1 vs REAL-TREND.

Frederick L Locke, Graeme Ball, Markqayne D Ray, Tony Li, Eve H Limbrick-Oldfield, Evan Popoff, Steve Kanters.

  To better understand the comparative effectiveness of axicabtagene ciloleucel (axi-cel) to historical standard of care (SoC) for the treatment of refractory diffused large B-cell lymphoma (DLBCL) among patients of Asian descent, we conducted a matching-adjusted indirect treatment comparison (MAIC) of the pivotal ZUMA-1 trial (NCT02348216) and the Asia-based REAL-TREND cohort. The individual patient data (IPD) from ZUMA-1 (n = 101 infused patients) used the 60-month data-cut, while the REAL-TREND cohort data consisted of aggregate data and pseudo-IPD derived from digitized curves. The outcomes were overall survival (OS), complete response (CR) and overall response rate (ORR), as reported in REAL-TREND. The MAIC weights were derived using age ≥ 60, sex, proportion of fourth line or higher (4L+) patients, international prognostic index (IPI; 0-1 vs. 2 vs. 3 vs. 4-5), and refractory to SCT. Sensitivity analyses explored the use of the intention to treat population, alternative variable alignment and use of central review assessed response. Some baseline characteristics were similar across ZUMA-1 and REAL-TREND, such as age and IPI scores, but key differences included proportion of 4L + patients (69% vs. 9%), of ECOG performance score 0-1 (100% vs. 59%), and type of refractoriness. The MAIC models aligned on prior lines and refractoriness, while differences in ECOG performance scores were captured through IPI. The resulting effective sample size for ZUMA-1 was 31.1. The estimated hazard ratio for OS was 0.27 (95% confidence interval [CI]: 0.15-0.50) and sensitivity analyses led to similar estimates. Strong effects were estimated for both ORR (odds ratio: 20.76; 95% CI: 7.18-60.02) and CR (odds ratio: 15.25; 95% CI: 6.84-33.98). The comparative efficacy of axi-cel relative to historical SoC was similar to that observed in studies restricted to Western settings. By providing outcomes data within a population of Asian-descent, we can provide better economic modeling to support reimbursements and improved access.

Keywords:  Asia; CAR T‐cell therapy; comparative effectiveness; diffused large B‐cell lymphoma; gene therapy; matching‐adjusted indirect treatment comparisons; standard of care

DOI:  https://doi.org/10.1002/hon.70100
Blood. 2025 May 13. pii: blood.2024025536. [Epub ahead of print]

Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells.

Corynn Kasap, Adila Izgutdina, Bonell Patiño-Escobar, Amrik Singh Kang, Nikhil Chilakapati, Naomi Akagi, Ananya Mishu Manoj, Haley Johnson, Tasfia Rashid, Juwita Werner, Abhilash Barpanda, Huimin Geng, Yu-Hsiu Tony Lin, Sham Rampersaud, Daniel Gil-Alós, Amin Sobh, Daphné Dupéré-Richer, Adolfo Aleman, Gianina Wicaksono, K M Kawehi Kelii, Radhika Dalal, Emilio Ramos, Anjanaa Vijayanarayanan, Kiran Lakhani, Fernando Salangsang, Paul Phojanakong, Juan Antonio Camara Serrano, Ons Zakraoui, Isa Tariq, Ajai Chari, Alfred Chung, Anupama Deepa Kumar, Thomas Martin, Jeffrey Lee Wolf, Sandy Wong, Veronica Steri, Mala Shanmugam, Lawrence H Boise, Tanja Kortemme, Samir Parekh, Elliot Stieglitz, Jonathan D Licht, William Karlon, Benjamin G Barwick, Arun Wiita.

Despite the success of BCMA-targeting CAR-Ts in multiple myeloma, patients with high-risk cytogenetic features still relapse most quickly and are in urgent need of additional therapeutic options. Here, we identify CD70, widely recognized as a favorable immunotherapy target in other cancers, as a specifically upregulated cell surface antigen in high-risk myeloma tumors. We use a structure-guided design to define a CD27-based anti-CD70 CAR-T design that outperforms all tested scFv-based CARs, leading to >80-fold improved CAR-T expansion in vivo. Epigenetic analysis via machine learning predicts key transcription factors and transcriptional networks driving CD70 upregulation in high-risk myeloma. Dual-targeting CAR-Ts against either CD70 or BCMA demonstrate a potential strategy to avoid antigen escape-mediated resistance. Together, these findings support the promise of targeting CD70 with optimized CAR-Ts in myeloma as well as future clinical translation of this approach.

DOI: https://doi.org/10.1182/blood.2024025536
Adv Ther. 2025 May 16.

Long-Term Transfusion Independence with Luspatercept Versus Epoetin Alfa in Erythropoiesis-Stimulating Agent-Naive, Lower-Risk Myelodysplastic Syndromes in the COMMANDS Trial.

Guillermo Garcia-Manero, Valeria Santini, Amer M Zeidan, Rami S Komrokji, Veronika Pozharskaya, Shelonitda Rose, Karen Keeperman, Yinzhi Lai, Sameer Kalsekar, Barkha Aggarwal, Dimana Miteva, David Valcárcel, Pierre Fenaux, Jake Shortt, Matteo Giovanni Della Porta, Uwe Platzbecker.

   INTRODUCTION: The efficacy of erythropoiesis-stimulating agents (ESAs) for transfusion-dependent (TD) anemia in lower-risk myelodysplastic syndromes (LR-MDS) is limited. Luspatercept achieved significantly greater rates of red blood cell (RBC) transfusion independence (TI) versus epoetin alfa (an ESA) in the phase 3 COMMANDS trial. This analysis assessed long-term RBC-TI, cumulative response, and safety with luspatercept in COMMANDS.
METHODS: Eligible patients aged ≥ 18 years, with ESA-naive, RBC TD LR-MDS were randomized 1:1 to receive luspatercept (1.0 mg/kg, titration to 1.75 mg/kg permitted) or epoetin alfa (450 IU/kg, titration to 1050 IU/kg). Disease assessment was carried out at week 24 (day 169) and every 24 weeks thereafter. Treatment continued until disease progression, lack of clinical benefit, unacceptable toxicity, or consent withdrawal.
RESULTS: At data cutoff (September 22, 2023; median follow-up: luspatercept 21.4 months, epoetin alfa 20.3 months), a greater proportion of patients treated with luspatercept (n = 182) versus epoetin alfa (n = 181) achieved a longest single RBC-TI period ≥ 1 year (44.5% vs. 27.6%; P = 0.0003) and ≥ 1.5 years (30.2% vs. 13.8%; P < 0.0001). Higher rates of RBC-TI ≥ 1.5 years with luspatercept over epoetin alfa were consistent across all prespecified subgroups, including patients with ring sideroblast-negative status and low baseline serum erythropoietin. Longer cumulative RBC-TI response [sum of all durations of RBC-TI for ≥ 12 weeks; week 1 to end of treatment (95% CI)] was observed with luspatercept [154.7 weeks (118.4-NR)] versus epoetin alfa [91.1 weeks (73.1-123.9)]. Rates of treatment-emergent adverse events, including asthenia and hypertension, generally decreased over time in both arms. Progression rates to high-risk MDS and acute myeloid leukemia were similarly low (< 5%) in both treatment arms.
CONCLUSIONS: These data demonstrated sustained, durable clinical benefit across subgroups and support luspatercept as the treatment of choice for anemia in patients with LR-MDS who are TD and ESA-naive.
TRIAL REGISTRATION NUMBER: NCT03682536.

Keywords:  Anemia; Epoetin alfa; Erythroid-stimulating agents; Luspatercept; Myelodysplastic syndromes; Transfusion-independence

DOI:  https://doi.org/10.1007/s12325-025-03208-5
Ther Adv Hematol. 2025 ;16 20406207251338942

Management of common autoimmune diseases in patients with myeloproliferative neoplasms treated with pegylated interferon alfa-case report, review of the literature and multidisciplinary clinical practice recommendations.

Axel Rüfer, Christoph Brand, Andrea de Gottardi, Stefan Fischli, Ralph Melzer, Urs Odermatt, Walter A Wuillemin, Sacha S Zeerleder.

  Pegylated interferons alfa are increasingly used in patients with myeloproliferative neoplasms (MPN) due to their potential disease-modifying effect. Ropeginterferon alfa-2b has been approved for patients with polycythemia vera (PV) with no symptomatic splenomegaly as first-line cytoreductive therapy, based on the results of the PROUD-PV/CONTINUATION-PV studies, documenting significantly higher rates of complete hematologic response (CHR) compared with hydroxyurea from 2-year timepoint onward. Although safety profile of pegylated interferons is overall good, interferon-related toxicities can occur. Focus of this article is on interferon-mediated autoimmune diseases. We describe two patients with PV treated with pegylated interferons alfa, one patient developed a cutaneous, paranasal sarcoidosis without any systemic symptoms and was successfully treated with topical steroids. The other patient developed widespread psoriatric skin lesions, which were treated with moderate effect with topical therapy with calcipotriene and betamethasone dipropionate foam, antidry calm lotion and in the course of the disease with ultraviolet light therapy (UVB). Only with methotrexate she achieved a nearly complete remission of the psoriasis. In both patients pegylated interferon was continued in view of the CHR and therefore the beneficial effect on MPN. We review the pertinent literature on the management of interferon-mediated autoimmune diseases in patients with MPN. As there is little published evidence on that topic, we propose multidisciplinary clinical practice recommendations based on available evidence and clinical experience in the management of patients with MPN treated with pegylated interferon alfa.

Keywords:  autoimmune diseases; case report; myeloproliferative neoplasms; pegylated interferons; polycythemia vera

DOI:  https://doi.org/10.1177/20406207251338942
Hemasphere. 2025 May;9(5): e70110

Optimizing therapy for relapsed/refractory classic Hodgkin lymphoma in the era of PD-1 blockade.

Thomas M Kuczmarski, Ryan C Lynch.

DOI: https://doi.org/10.1002/hem3.70110
Cancers (Basel). 2025 Apr 22. pii: 1389. [Epub ahead of print]17(9):

Real-World Treatment Outcomes of Different Sequencing Options with Daratumumab, Lenalidomide, and Dexamethasone in Patients with Transplant-Ineligible Multiple Myeloma in Japan.

Kazuhito Suzuki, Yuma Fujimori, Chika Sakai, Hiroaki Tsuchiya, Yosuke Koroki.

  Multiple myeloma (MM) is a hematologic malignancy characterized by monoclonal proliferation of plasma cells that leads to bone disease, including lytic lesions and osteoporosis [...].

Keywords:  daratumumab; lenalidomide; newly diagnosed multiple myeloma; overall survival; real-world evidence; treatment sequence

DOI:  https://doi.org/10.3390/cancers17091389
AAPS PharmSciTech. 2025 May 13. 26(5): 131

Dasatinib Pharmacokinetics and Advanced Nanocarrier Strategies: from Systemic Limitations to Targeted Success.

Mahesha Keerikkadu, Pragathi Devanand Bangera, Vamshi Krishna Tippavajhala, Mahalaxmi Rathnanand.

  Dasatinib (DSB) is a second-generation tyrosine kinase inhibitor widely used for treating chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Though clinically effective, DSB has some pharmacokinetic drawbacks evidenced by rapid systemic clearance, low oral bioavailability, and poor aqueous solubility requiring high doses for therapeutic action. Novel formulation strategies like solid dispersions, liposomal formulations, and PEGylated and hybrid nanoparticles enhance DSB's pharmacokinetic and pharmacodynamic profiles by enhancing drug solubility, stability, and controlled release. In addition, through these targeted drug-delivery systems based on ligand-functionalized nanoparticles and antibody-drug conjugates-the tumor-targeted DSB is allowed selective accumulation at the tumor site, causing fewer off-target effects and lessening systemic toxicity while maximizing effectiveness. These approaches are geared toward utilizing nanotechnology to improve intracellular drug uptake and extend the circulation time to optimize antitumor efficacy. Overall, those advances in drug delivery systems could greatly boost the therapeutic efficacy of DSB by providing better bioavailability, controlled release, and targeted distribution. Such advances would increase treatment success in CML and Ph + ALL and expand DSB's potential clinical applications toward other malignancies. Research concerning the delivery of DSB with nanocarriers and ligand-mediated targeting strategies should bear further fruits to augment DSB therapy in oncology.

Keywords:  BCR-ABL kinase; Dasatinib; Nanocarriers; Tumor targeting; Tyrosine kinase

DOI:  https://doi.org/10.1208/s12249-025-03130-7
Cancer. 2025 May 15. 131(10): e35880

Has the time for treatment-free remission in Philadelphia chromosome-positive acute lymphoblastic leukemia arrived?

Ehab Atallah, Jeffrey H Lipton.



Keywords:  Philadelphia chromosome; acute lymphocytic leukemia (ALL); sustained deep molecular remission; treatment‐free remission

DOI:  https://doi.org/10.1002/cncr.35880