bims-hemali Biomed News
on Hematologic malignancies
Issue of 2025–03–16
fifteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Phase 2 study of chidamide in combination with CAG and venetoclax-azacitidine in older patients with newly diagnosed acute myeloid leukemia.
  2. Nivolumab plus relatlimab in patients with relapsed or progressed B-cell malignancies in RELATIVITY-022.
  3. Continuous R-DA-EDOCH alternated with high-dose Ara-C induces deep remission and overcomes high-risk factors in young patients with newly diagnosed mantle cell lymphoma.
  4. Thalidomide-based regimen shows promising efficacy in large granular lymphocytic leukemia: a multicenter phase II study.
  5. Efficacy of Combined CD38 and PD1 Inhibition with Isatuximab and Cemiplimab for Relapsed/Refractory NK/T-Cell Lymphoma.
  6. Subgroup analysis of elderly patients (≥60 years) with diffuse large B-cell lymphoma in the phase 3 POLARIX study.
  7. Twin pregnancy during treatment with asciminib for chronic myeloid leukemia - a case report.
  8. Azacitidine and venetoclax for HR-MDS: election results pending.
  9. High-Risk Nonsecretory Multiple Myeloma With Poor Response to Daratumumab-Based Chemotherapy.
  10. Combined autologous hematopoietic stem cell transplantation and CD19 CAR T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma with TP53 mutation: A case report.
  11. Antibody-Based and Other Novel Agents in Adult B-Cell Acute Lymphoblastic Leukemia.
  12. Determination of the appropriate chemotherapy for patients aged 80 years or older with diffuse large B cell lymphoma.
  13. Waldenström Macroglobulinemia - A State-of-the-Art Review: Part 2- Focus on Therapy.
  14. Factors associated with survival following allogeneic transplantation for myeloid neoplasms harboring TP53 mutations.
  15. Impact of treatment for adolescent and young adults with essential thrombocythemia and polycythemia vera.
  1. Front Immunol. 2025 ;16 1525110
    Phase 2 study of chidamide in combination with CAG and venetoclax-azacitidine in older patients with newly diagnosed acute myeloid leukemia.
    Qingyang Liu, Jingjing Yang, Lei Lv, Xiawei Zhang, Meng Li, Lingmin Xu, Sai Huang, Yu Jing, Liping Dou.
       Introduction: Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. DNA methyltransferases (DNMTs) and histone-deacetylases (HDACs) are key regulators of gene expression in cells and have been investigated as important therapeutic targets. However, their effects remains unclear as induction therapy for AML.
    Methods: Previously untreated AML patients aged 60 years and over (N=40) were enrolled into this single arm, open-label, phase 2 study to evaluate the clinical efficacy and safety of chidamide combined with CAG and venetoclax-azacitidine (referred to as CACAG-VEN) in elderly AML patients (ClinicalTrials.gov:NCT05659992). All patients received induction treatment with aclarubicin (10 mg/m2/d on days 1, 3, and 5), azacitidine (75 mg/m2 on days 1-7), cytarabine (75 mg/m2 bid on days 1-5), chidamide (30 mg, twice/week for 2 weeks), and venetoclax (100 mg on day 1, 200 mg on day 2, 400 mg on days 3-14). Granulocyte colony-stimulating factor 5 mg/kg/day was administered.
    Results: Theoverall response rate was 97.5%, with a composite complete response (CRc) rate of 85.0% after one cycle of CACAG-VEN. Patients with adverse risk according to the ELN guidelines had CRc rates of 81.3%. No patients experienced early death within 30 days of therapy initiation. Grade 3 - 4 non-hematological adverse events included febrile neutropenia in 15 (37.5%) of 40 patients, pneumonia in three (7.5%), sepsis in two (5.0%) and blood bilirubin increase in one (2.5%). The 12-month overall survival rate was 73.4% (95% CI: 55.9-84.8%). The median time to recovery was 15.0 (IQR 10.0-19.5) days for platelets ≥ 20000/mL and 13.0 (IQR 10.5-17.0) days for an absolute neutrophil count ≥ 1000 cells/mL after induction therapy.
    Discussion: In conclusion, chidamide in combination with CAG and venetoclaxazacitidine was effective and well tolerated in elderly patients with AML.
    Clinical trial registration: https://www.clinicaltrials.gov/, identifier NCT05659992.
    Keywords:  CACAG-VEN regimen; acute myeloid leukemia; azacitidine; older patients; venetoclax
    DOI:  https://doi.org/10.3389/fimmu.2025.1525110
  2. Blood Adv. 2025 Mar 03. pii: bloodadvances.2024015086. [Epub ahead of print]
    Nivolumab plus relatlimab in patients with relapsed or progressed B-cell malignancies in RELATIVITY-022.
    Ajay K Gopal, Philippe Armand, Sattva S Neelapu, Nancy L Bartlett, Stephen E Spurgeon, John Kuruvilla, Kerry J Savage, John P Leonard, Arnold B Gelb, Nasir Ahmed, Shiqi Dong, Sai Praneeth Bathena, Rasika Suryawanshi, Qun Jenny Wu, Sheen Wang, Douglas E Gladstone.
      Despite high response rates, anti-PD-1 therapy monotherapy eventually fails in most patients with relapsed or refractory Hodgkin Lymphoma (HL) and is generally ineffective in most other B-cell malignancies. The lymphocyte activation gene 3 (LAG-3) cell-surface receptor represents another immune checkpoint molecule that can be targeted to induce remissions in these diseases; dual inhibition of PD-1 and LAG-3 is approved for treating advanced melanoma. We performed a multicenter phase 1/2a open-label study of the anti-LAG-3 antibody relatlimab (RELATIVITY-022) administered as monotherapy or in combination with nivolumab in patients with relapsed or refractory B-cell malignancies. In total, 106 patients were treated and no dose limiting toxicities were observed during escalation. The recommended phase 2 dose was relatlimab 240 mg as monotherapy or nivolumab 240 mg plus relatlimab 160 mg, administered every 2 weeks. No unexpected safety signals were observed compared to single agent anti-PD-1 therapy. In the HL expansion cohorts, overall response rate (ORR) was 62% and complete response rate (CRR) was 19% in anti-PD-(L)1 naïve patients (n = 21), with a median PFS of 19 months; ORR was 15% and CRR 0%, median PFS 6 months in anti-PD-(L)1 progressed patients (n = 20). In the DLBCL cohort, ORR was 7% with no CRs (n = 15), and median PFS was 2 months. Nivolumab plus relatlimab appeared to be safe and tolerable. Efficacy in PD-1 naïve HL patients was encouraging, although the contribution of relatlimab to overall efficacy of the combination needs to be further evaluated. Clinicaltrials.gov; NCT02061761.
    DOI:  https://doi.org/10.1182/bloodadvances.2024015086
  3. Cancer Biol Med. 2025 Mar 12. pii: j.issn.2095-3941.2024.0200. [Epub ahead of print]22(2):
    Continuous R-DA-EDOCH alternated with high-dose Ara-C induces deep remission and overcomes high-risk factors in young patients with newly diagnosed mantle cell lymphoma.
    Yi Wang, Yuting Yan, Dandan Shan, Jiawen Chen, Wei Liu, Tingyu Wang, Gang An, Weiwei Sui, Wenyang Huang, Wenjie Xiong, Huimin Liu, Qi Sun, Huijun Wang, Zhijian Xiao, Jianxiang Wang, Lugui Qiu, Dehui Zou, Shuhua Yi.
       OBJECTIVE: Our previous studies have indicated potentially higher proliferative activity of tumor cells in Chinese patients with mantle-cell lymphoma (MCL) than those in Western. Given the success and tolerability of R-DA-EDOCH immunochemotherapy in treating aggressive B-cell lymphomas, we designed a prospective, phase 3 trial to explore the efficacy and safety of alternating R-DA-EDOCH/R-DHAP induction therapy for young patients with newly diagnosed MCL. The primary endpoint was the complete remission rate (CRR) at the end of induction (EOI).
    METHODS: A total of 55 patients were enrolled. The CRR at the EOI was 89.1% [95% confidence interval (CI) 78%-96%], and the overall response rate was 98.1% (95% CI 90%-100%). Most patients with bone marrow involvement quickly attained minimal residual disease (MRD) negative status, with a 95.7% rate at the EOI.
    RESULTS: The 3-year progression-free survival (PFS) and overall survival rates were 66.3% and 83.2%, respectively. No patients discontinued treatment because of adverse events. Univariate analysis identified pathologic morphology and TP53 mutations as risk factors for PFS. However, high tumor proliferative activity and certain cytogenetic abnormalities showed no significant adverse prognostic significance.
    CONCLUSIONS: Intensive therapy based on a high cytarabine dose and continuously administered EDOCH achieved a high MRD-negative rate and provides an optional induction choice for young patients with MCL with high-risk factors.
    Keywords:  Mantle cell lymphoma; adverse events; high-risk factors; immunochemotherapy; minimal residual disease
    DOI:  https://doi.org/10.20892/j.issn.2095-3941.2024.0200
  4. Signal Transduct Target Ther. 2025 Mar 12. 10(1): 85
    Thalidomide-based regimen shows promising efficacy in large granular lymphocytic leukemia: a multicenter phase II study.
    Ying Yu, Yuxi Li, Rui Cui, Yuting Yan, Fei Li, Yan Chen, Tingyu Wang, Xiaoli Hu, Yaqing Feng, Tengteng Yu, Yanshan Huang, Jingwen Sun, Rui Lyu, Wenjie Xiong, Qi Wang, Wei Liu, Gang An, Weiwei Sui, Yan Xu, Wenyang Huang, Dehui Zou, Huijun Wang, Zhijian Xiao, Jianxiang Wang, Lugui Qiu, Shuhua Yi.
      Large granular lymphocytic leukemia (LGLL) is characterized by the clonal proliferation of cytotoxic T lymphocytes or NK cells. Standard first-line immunosuppressive treatments have limitations, achieving complete remission (CR) rates of up to 50%. Immune system dysregulation is implicated in LGLL. Promising results for thalidomide, an immunomodulatory drug, combined with prednisone and methotrexate (TPM), were observed in our pilot study. This multicenter study evaluated the efficacy and safety of a thalidomide, prednisone, and methotrexate (TPM) regimen in 52 symptomatic, methotrexate- and thalidomide-naive LGLL patients from June 2020 to August 2022. Thalidomide (100 mg daily for up to 24 months), prednisone (0.5-1.0 mg/kg every other day, tapered after 3 months), and methotrexate (10 mg/m2 weekly for up to 12 months) were administered. The primary objective was to determine the CR rate. The median follow-up duration was 29.0 months (range: 4.0-42.0). Forty-seven patients (90.4%) achieved hematological and symptomatic responses. Thirty-nine patients (75.0%) achieved CR. The median time to response was 3.0 months (range: 3.0-9.0). The median progression-free survival was 40.0 months (95% confidence interval (CI): 38.0-42.0), and the median duration of response was 39.0 months (95% CI: 36.1-41.9). The most common adverse event was peripheral neuropathy (24.1%), most of which (84.6%) were grades 1-2. Four patients experienced grade ≥3 adverse events. In conclusion, the TPM regimen was an effective and safe treatment for symptomatic LGLL patients, with a particularly high CR rate. This trial was registered at www.clinicaltrials.gov (#NCT04453345).
    DOI:  https://doi.org/10.1038/s41392-025-02164-4
  5. Blood. 2025 Mar 12. pii: blood.2024027109. [Epub ahead of print]
    Efficacy of Combined CD38 and PD1 Inhibition with Isatuximab and Cemiplimab for Relapsed/Refractory NK/T-Cell Lymphoma.
    Seok Jin Kim, Jing Quan Lim, Sang Eun Yoon, Deok-Hwan Yang, Ji Hyun Lee, Sung Yong Oh, Yoon Seok Choi, Seong Hyun Jeong, Min Kyoung Kim, Sung-Nam Lim, Junhun Cho, Bon Park, Kyung Ju Ryu, Seunghyun Choi, Yoon Park, Kerry May Huifen Lim, Nur Ayuni Binte Muhammad Taib, Choon Kiat Ong, Soon Thye Lim, Won Seog Kim.
      This study aimed to assess the efficacy and safety of combining cemiplimab, an anti-PD1 antibody, with isatuximab, an anti-CD38 antibody, in relapsed or refractory extranodal NK/T-cell lymphoma (R/R ENKTL). The hypothesis was that CD38 blockade could enhance the antitumor activity of PD1 inhibitors. Eligible patients received cemiplimab (250 mg on days 1 and 15) and isatuximab (10 mg/kg on days 2 and 16) intravenously every four weeks for six cycles. Responders then received cemiplimab (350 mg) and isatuximab (10 mg/kg) every three weeks for up to 24 months. The primary endpoint was the complete response (CR) rate based on the best response. Out of 37 patients enrolled, the CR rate was 51% (19/37), exceeding the primary endpoint of 40%, and the objective response rate was 65% (24/37). After a median follow-up of 30.2 months (95% CI: 25.6-34.8 months), the median progression-free survival was 9.5 months (95% CI: 1.4-17.6 months), while the median overall survival had not yet been reached. Patients achieving CR received a median of 28 cycles (range: 4-33), and the median duration of response for responders (n = 24) was 29.4 months (95% CI: 15.4-43.4 months). Structural variations disrupting the 3'-UTR of PD-L1 and high PD-L1 expression were observed in responders. Most adverse events were mild (grade 1-2), with grade ≥3 events (32%) and no treatment-related deaths. The combination of isatuximab and cemiplimab demonstrated sustained antitumor activity and a manageable safety profile in R/R ENKTL. This phase II trial is registered at www.clinicaltrials.gov as #NCT04763616.
    DOI:  https://doi.org/10.1182/blood.2024027109
  6. Blood Adv. 2025 Mar 14. pii: bloodadvances.2024014707. [Epub ahead of print]
    Subgroup analysis of elderly patients (≥60 years) with diffuse large B-cell lymphoma in the phase 3 POLARIX study.
    Bei Hu, Patrick M Reagan, Laurie H Sehn, Jeff P Sharman, Mark Hertzberg, Huilai Zhang, Austin I Kim, Charles Herbaux, Lysiane Molina, Dai Maruyama, Frank Stenner, Saibah Chohan, Rucha Kothari, Connie Lee Batlevi, Jamie Hirata, Deniz Sahin, Calvin Lee, Matthew Sugidono, Hervé Tilly.
      In the phase 3 POLARIX study, polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) improved progression-free survival (PFS) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). This post hoc subgroup analysis of POLARIX evaluated the efficacy and safety of Pola-R-CHP versus R-CHOP in elderly patients ≥60, ≥65, ≥70, and ≥75 years. As of June 15, 2022 (median follow-up 40 months), 629 patients ≥60 years were included (Pola-R-CHP, n = 311; R-CHOP, n = 318). Clinically meaningful improvements in PFS with Pola-R-CHP versus R-CHOP were observed across all age groups, particularly in patients ≥70 years whereby the risk of disease progression, relapse or death was reduced by 37% (unstratified hazard ratio [HR] 0.63; 95% confidence interval [CI]: 0.41-0.96). In patients ≥ 60 years, overall survival was similar with Pola-R-CHP versus R-CHOP (unstratified HR 0. 99; 95% CI: 0.67 -1.47 ). Safety profiles were similar for Pola-R-CHP versus R-CHOP among patients ≥60 years, including rates of grade 3-4 adverse events (AEs; 62.7% vs 61.5%), grade 3-5 infections (15.0% vs 12.9%), and grade 5 AEs (3.6% vs 3.2%); no novel toxicities were reported. Incidence of grade 3-4 febrile neutropenia was higher with Pola-R-CHP than R-CHOP (16.3% vs 7.6%), highlighting the importance of G-CSF prophylaxis in elderly patients receiving Pola-R-CHP. The benefit-risk profile favored Pola-R-CHP versus R-CHOP in elderly patients with previously untreated DLBCL. This trial was registered at ClinicalTrials.gov as #NCT03274492.
    DOI:  https://doi.org/10.1182/bloodadvances.2024014707
  7. Ann Hematol. 2025 Mar 08.
    Twin pregnancy during treatment with asciminib for chronic myeloid leukemia - a case report.
    Géssika B G M Gutierrez de Moraes Pereira, Victor A Rocha, Paulo Victor R Barbosa, Christopher Cralcev, Alice V de Jesus, Mariana B Spadoni, Teresa Vilela V Pereira, João Paulo C Magalhães, Gislaine O Duarte, Guilherme Duffles, Felipe S Maia, Fernanda Surita, José Paulo S Guida, Carmino Antonio de Souza, Maria Laura Costa, Katia B B Pagnano.
      Managing chronic myeloid leukemia during pregnancy presents significant challenges, with limited treatment options available depending on the stage of pregnancy. All existing tyrosine kinase inhibitors are considered teratogenic, especially during the first trimester and should be avoided. In this case report, we detail the successful, unplanned dichorionic diamniotic twin pregnancy of a patient with chronic-phase myeloid leukemia previously resistant to imatinib and dasatinib who was exposed to the allosteric tyrosine kinase inhibitor asciminib during the early weeks of gestation. Upon confirmation of the pregnancy, asciminib was discontinued, and the patient was treated with pegylated interferon. The patient developed preeclampsia, and the twins were delivered prematurely via cesarean section. No other abnormalities were observed in the newborns. During her pregnancy, the patient experienced a loss of the major molecular response; however, she regained it within two months of resuming asciminib after giving birth. To our knowledge, this case represents the first report of a twin pregnancy during asciminib treatment.
    Keywords:  Asciminib; Chronic myeloid leukemia; Pregnancy; Tyrosine kinase inhibitors
    DOI:  https://doi.org/10.1007/s00277-025-06238-9
  8. Blood. 2025 Mar 13. 145(11): 1099-1100
    Azacitidine and venetoclax for HR-MDS: election results pending.
    Sangeetha Venugopal, Mikkael A Sekeres.
      
    DOI:  https://doi.org/10.1182/blood.2024027567
  9. Cureus. 2025 Feb;17(2): e78665
    High-Risk Nonsecretory Multiple Myeloma With Poor Response to Daratumumab-Based Chemotherapy.
    Surendra Khanal, Rameela Rizvi, Christopher March.
      Nonsecretory multiple myeloma (NSMM) is the variant of multiple myeloma defined by no detectable M protein secretion in serum or urine electrophoresis. Due to the lack of detectable M spike, diagnosis is often challenging and relies on bone marrow studies. As studies specifically focusing on NSMM are lacking, the current treatment guidelines are based on studies in secretory multiple myeloma. In this case report, we describe a 77-year-old female patient with a typical presentation of NSMM who did not respond to a chemotherapy regimen based on daratumumab.
    Keywords:  clinical case report; daratumumab; lenalidomide; multiple myeloma prognosis; nonsecretory multiple myeloma; serum free light chain
    DOI:  https://doi.org/10.7759/cureus.78665
  10. SAGE Open Med Case Rep. 2025 ;13 2050313X241306236
    Combined autologous hematopoietic stem cell transplantation and CD19 CAR T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma with TP53 mutation: A case report.
    Ziyi Cai, Dongmei Zou, Qiang Ma, Wanling Sun, Yixian Guo.
      Despite advancements in the treatment of diffuse large B-cell lymphoma, including CAR T-cell therapy, TP53 mutations remain a significant negative prognostic factor in patients with relapsed/refractory diffuse large B-cell lymphoma. The combination of autologous stem cell transplantation and CAR T-cell therapy may enhance long-term prognosis and reduce adverse effects, including severe cytokine release syndrome. This case report presents a 41-year-old man with relapsed/refractory diffuse large B-cell lymphoma harboring TP53 mutations who underwent autologous stem cell transplantation combined with CD19 CAR T-cell therapy. Two years posttreatment, the patient remains in sustained complete remission, highlighting the potential efficacy of this combination approach for relapsed/refractory diffuse large B-cell lymphoma with TP53 mutation.
    Keywords:  CAR T-cell therapy; TP53 mutation; autologous hematopoietic stem cell transplantation; relapsed/refractory diffuse large B-cell lymphoma
    DOI:  https://doi.org/10.1177/2050313X241306236
  11. Cancers (Basel). 2025 Feb 25. pii: 779. [Epub ahead of print]17(5):
    Antibody-Based and Other Novel Agents in Adult B-Cell Acute Lymphoblastic Leukemia.
    Clifford M Csizmar, Mark R Litzow, Antoine N Saliba.
      Despite notable progress in managing B-cell acute lymphoblastic leukemia (B-ALL) over recent decades, particularly in pediatric cohorts where the 5-year overall survival (OS) reaches 90%, outcomes for the 10-15% with relapsed and refractory disease remain unfavorable. This disparity is further accentuated in adults, where individuals over the age of 40 years undergoing aggressive multiagent chemotherapy continue to have lower survival rates. While the adoption of pediatric-inspired treatment protocols has enhanced complete remission (CR) rates among younger adults, 20-30% of these patients experience relapse, resulting in a subsequent 5-year OS rate of 40-50%. For relapsed B-ALL in adults, there is no universally accepted standard salvage therapy, and the median OS is short. The cornerstone of B-ALL treatment continues to be the utilization of combined cytotoxic chemotherapy regimens to maximize early and durable disease control. In this manuscript, we go beyond the multiagent chemotherapy medications developed prior to the 1980s and focus on the incorporation of antibody-based therapy for B-ALL with an eye on existing and upcoming approved indications for blinatumomab, inotuzumab ozogamicin, other monoclonal antibodies, and chimeric antigen receptor (CAR) T cell products in frontline and relapsed/refractory settings. In addition, we discuss emerging investigational therapies that harness the therapeutic vulnerabilities of the disease through targeting apoptosis, modifying epigenetics, and inhibiting the mTOR pathway.
    Keywords:  B-cell acute lymphoblastic leukemia; CAR T-cell therapy; blinatumomab; immunotherapy; inotuzumab ozogamicin; targeted therapies
    DOI:  https://doi.org/10.3390/cancers17050779
  12. Leuk Lymphoma. 2025 Mar 03. 1-12
    Determination of the appropriate chemotherapy for patients aged 80 years or older with diffuse large B cell lymphoma.
    Min Jung Kim, Junhun Cho, Won Seog Kim, Seok Jin Kim, Sang Eun Yoon.
      This is a retrospective study conducted to determine whether there is an optimal regimen for elderly diffuse large B-cell lymphoma (DLBCL) patients. We selected patients aged 80 years or older who received the frontline chemoimmunotherapy of standard-dose rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), reduced dose of R-CHOP (R-miniCHOP), or rituximab and bendamustine (BR). Patients with standard dose of R-CHOP presented a better overall response rate than those with R-miniCHOP (p = 0.047). However, there was no significant difference in progression-free survival (PFS) or overall survival (OS) among the groups. Eastern Cooperative Oncology Group performance status of 0 or 1, serum albumin ≥3.5 g/dL, early stage, and GCB subtype were the factors associated with superior PFS and OS. In conclusion, no single regimen was found to be superior for elderly DLBCL patients. Rather than selecting regimen depending on sole age, comprehensive evaluation should be done before chemotherapy initiation.
    Keywords:  Diffuse large B-cell lymphoma; anthracycline-containing regimen; elderly patient
    DOI:  https://doi.org/10.1080/10428194.2025.2471500
  13. Mediterr J Hematol Infect Dis. 2025 ;17(1): e2025015
    Waldenström Macroglobulinemia - A State-of-the-Art Review: Part 2- Focus on Therapy.
    Michele Bibas, Shayna Sarosiek, Jorge J Castillo.
      The diagnosis and treatment of Waldenstrom macroglobulinemia (WM) are the subjects of this two-part review, which aims to provide current and thorough knowledge of these topics. The first portion of the study, previously published, investigated the epidemiology, etiology, clinicopathological aspects, differential diagnosis, prognostic factors, and impact on WM-specific groups. Specifically, this second section examines both the standard consolidated method and the new therapeutic strategy to handle the complex topic of the treatment of WM.
    Key Points: WM has no cure, but therapies can improve survival. Treatment for WM/LPL patients should be initiated when they exhibit symptoms, and the IgM level should not determine WM treatment.Current guidelines suggest various initial personalized therapy treatments, typically chemoimmunotherapy (CIT) or BTK inhibitors (BTKi).Patients with WM can be put into three groups based on their MYD88 and CXCR4 mutational status: those with MYD88 mutations but no CXCR4 mutations (MYD88MUT/CXCR4WT), those with both MYD88 and CXCR4 mutations (MYD88MUT/CXCR4MUT) and those who do not have both MYD88 and CXCR4 mutations (MYD88WT/CXCR4WT).The objective of treatment is to alleviate symptoms and mitigate the risk of organ impairment.The timing of response evaluations, including BM, should be established on a case-by-case basis, informed by clinical and laboratory assessments.Patients with relapsed/refractory WM following chemotherapy and covalent Bruton tyrosine kinase inhibitors may choose non-covalent Bruton tyrosine kinase inhibitors, novel anti-CD20 monoclonal antibodies, BCL-2 inhibitors, or more intensive chemotherapy regimens.Patients who are younger and healthier and have not responded to both CIT and BTKi may be good candidates for an autologous stem cell transplant (ASCT).Second-generation anti-CD19 CAR T cells exhibit anti-WM activity in both in vitro and in vivo settings.From 2.4% to 11% of patients with WM undergo histological transformation, predominantly to diffuse large B-cell lymphoma (DLBCL). The median duration between diagnosis and transformation is 4.6 years.WM patients have a higher risk of secondary cancers.HSV and HZV prophylaxis may be beneficial for patients needing extensive treatment. Screening for Hepatitis B is necessary. Pneumocystis jiroveci prophylaxis is highly recommended. SARS-CoV- 2 and seasonal flu vaccines should be available to all WM patients.
    Keywords:  Waldenstrom macroglobulinemia
    DOI:  https://doi.org/10.4084/MJHID.2025.015
  14. Blood Adv. 2025 Mar 14. pii: bloodadvances.2024015335. [Epub ahead of print]
    Factors associated with survival following allogeneic transplantation for myeloid neoplasms harboring TP53 mutations.
    Anmol Baranwal, Kimberly Langer, Vedavyas Gannamani, Danielle Rud, Alia Cibich, Caner Saygin, Mariam T Nawas, Talha Badar, Mohamed A Kharfan-Dabaja, Ernesto Ayala, Vivek Roy, James M Foran, Hemant S Murthy, Madiha Iqbal, Jeanne M Palmer, Lisa Sproat, Saurabh Chhabra, Nandita Khera, Mehrdad Hefazi, Abhishek A Mangaonkar, William J Hogan, Mark R Litzow, Hassan B Alkhateeb, Ayalew Tefferi, Chung Hoow Kok, Guru Subramanian Guru Murthy, Anand A Patel, Ashish Bajel, Devendra K Hiwase, Mithun Vinod Shah.
      Allogeneic stem cell transplant (alloHCT) is considered for all patients with myeloid neoplasms (MN) harboring TP53-mutations (TP53mut). The aim of this international study across 7 transplant centers in USA and Australia was to identify factors associated with improved post-alloHCT survival. Of 134 TP53mut MN cases who underwent alloHCT, 80% harbored complex karyotype (CK); 94% of TP53 variants were localized to the DNA-binding domain (DBD). Most common co-mutations were ASXL1 (7%), TET2 (7%), and DNMT3A (6%). Median post-HCT survival was 1.03 years and OS at 1-, 2-, and 3-years was 51.4%, 35.1%, and 25.1%, respectively. One-hundred three (76.9%) cases met the International Consensus Classification (ICC) criteria for myeloid neoplasms with mutated TP53 (referred to as ICC-defined TP53mut MN hereafter). 3-year OS of ICC-defined TP53mut was significantly shorter compared to other TP53mut MN (3-year OS 16.9 vs. 54.9%, P=0.002). ICC-defined TP53mut MN was independently associated with inferior OS (HR 2.62, P=0.019). The presence of non-DBD TP53mut only (HR 3.40, P=0.005), DNMT3A co-mutation (HR 2.64, P=0.016), and pre-alloHCT bone marrow blasts ≥5% (HR 2.76, P=0.006) were independently associated with inferior RFS, while melphalan-based conditioning was associated with superior RFS (HR 0.52, P=0.005). Combining these variables, we constructed a hierarchical model that stratified patients into low-, intermediate, and high-risk categories with 1-year RFS of 81.3%, 31.3% and 6.7%, respectively (P<0.001). In conclusion, a subset of MN harboring TP53mut who have low blasts pre-alloHCT and received melphalan-based conditioning derived long-term benefit from alloHCT.
    DOI:  https://doi.org/10.1182/bloodadvances.2024015335
  15. Leukemia. 2025 Mar 12.
    Impact of treatment for adolescent and young adults with essential thrombocythemia and polycythemia vera.
    Yan Beauverd, Jean-Christophe Ianotto, Kyaw Htin Thaw, Marta Sobas, Parvis Sadjadian, Natalia Curto-Garcia, Lee-Yung Shih, Timothy Devos, Dorota Krochmalczyk, Serena Galli, Maria Bieniaszewska, Ilona Seferynska, Mary Frances McMullin, Anna Armatys, Adrianna Spalek, Joanna Waclaw, Mihnea Tudor Zdrenghea, Laurence Legros, Francois Girodon, Krzysztof Lewandowski, Beatriz Bellosillo, Jan Samuelsson, Aitor Abuin Blanco, Pascale Cony-Makhoul, Angela Collins, Chloe James, Rajko Kusec, Marie Lauermannova, Maria Soledad Noya, Malgorzata Skowronek, Lukasz Szukalski, Anna Szmigielska-Kaplon, Marielle Wondergem, Iryna Dudchenko, Joanna Gora-Tybor, Kamel Laribi, Anna Kulikowska de Nałęcz, Jean-Loup Demory, Katell Le Dû, Sonja Zweegman, Carlos Besses Raebel, Radek C Skoda, Stephane Giraudier, Martin Griesshammer, Jean-Jacques Kiladjian, Claire N Harrison.
      Essential thrombocythemia (ET) and polycythemia vera (PV) are rare in adolescent and young adult (AYA). These conditions, similar to those in older patients, are linked with thrombotic complications and the potential progression to secondary myelofibrosis (sMF). This retrospective study of ET and PV patients diagnosed before age 25 evaluated complication rates and impact of cytoreductive drugs on outcomes. Among 348 patients (278 ET, 70 PV) with a median age of 20 years, the of thrombotic events was 1.9 per 100 patient-years. Risk factors for thrombosis included elevated white blood cell count (>11 × 109/L) (HR: 2.7, p = 0.012) and absence of splenomegaly at diagnosis (HR: 5.7, p = 0.026), while cytoreductive drugs did not reduce this risk. The incidence of sMF was 0.7 per 100 patient-years. CALR mutation (HR: 6.0, p < 0.001) and a history of thrombosis (HR: 3.8, p = 0.015) were associated with sMF risk. Interferon as a first-line treatment significantly improved myelofibrosis-free survival compared to other treatments or the absence of cytoreduction (p = 0.046). Although cytoreduction did not affect thrombotic event, early interferon use reduced sMF risk. These findings support interferon use to mitigate sMF risk in AYA ET and PV patients.
    DOI:  https://doi.org/10.1038/s41375-025-02545-2
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