bims-hemali Biomed News
on Hematologic malignancies
Issue of 2025–06–08
fifteen papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Cytogenetic Response to Asciminib in Chronic Myeloid Leukemia With the e19a2 Micro BCR::ABL1 Transcript: A Case Report.
  2. KIR3DL1-HLA-Bw status in CML is associated with achievement of TFR: the POKSTIC trial, a multicenter observational study.
  3. Indirect comparison of epcoritamab vs chemoimmunotherapy, mosunetuzumab, or odronextamab in follicular lymphoma.
  4. Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma.
  5. CD302 predicts achievement of deep molecular response in patients with chronic myeloid leukemia treated with imatinib.
  6. Outcome of Chronic Myeloid Leukemia Patients Not in Deep Molecular Response: Results From the GIMEMA LabNet CML Network Database.
  7. [Drug-induced sarcoidosis-like reaction due to dasatinib in the lung of a patient with chronic myeloid leukemia].
  8. Ixazomib-lenalidomid-dexamethasone (IRd) in relapsed refractory multiple myeloma (RRMM)-multicenter real-world analysis from Germany and comparative review of the literature.
  9. Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor-Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321).
  10. Clinical outcomes of newly diagnosed PCNSL treated with rituximab-methotrexate-cytarabine with or without ibrutinib: a retrospective study.
  11. Novel Therapies in Primary Central Nervous System Lymphoma.
  12. Zanubrutinib and Venetoclax for Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With and Without Del(17p)/TP53 Mutation: SEQUOIA Arm D Results.
  13. Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma.
  14. Investigation of the mechanism of hypertension caused by BTKi in the treatment of hematologic diseases.
  15. Indirect treatment comparisons of momelotinib vs pacritinib safety and anemia outcomes in patients with myelofibrosis.
  1. Cureus. 2025 May;17(5): e83363
    Cytogenetic Response to Asciminib in Chronic Myeloid Leukemia With the e19a2 Micro BCR::ABL1 Transcript: A Case Report.
    Takuya Terakawa, Yasuhiro Shingai, Yoshiki Matsuoka, Yuka Amemiya, Wataru Nakahara, Yuma Tada, Sayako Yuda, Shigeo Fuji, Jun Ishikawa, Takafumi Yokota.
      Chronic myeloid leukemia (CML) is classified into three subtypes based on the BCR breakpoint, the rarest of which is micro BCR::ABL1 (also known as e19a2 BCR::ABL1), which encodes a P230 fusion protein. CML patients with the e19a2 transcript are known to have a poor prognosis. Although second-generation tyrosine kinase inhibitors (TKIs) may be effective for this subtype, asciminib, a novel BCR::ABL1 inhibitor that specifically targets the ABL1 myristoyl pocket, has only been shown to be effective in patients with the major BCR::ABL1 transcript, with limited data on the micro BCR::ABL1 subtype. Here, we report a case of a CML patient with the e19a2 transcript who was intolerant to four TKIs but achieved complete cytogenetic response with asciminib. Our case suggests that asciminib, in addition to showing promising outcomes in CML patients with the major BCR::ABL1 transcript, is an effective treatment option for CML patients with the e19a2 micro BCR::ABL1 transcript.
    Keywords:  asciminib; chronic myeloid leukemia; complete cytogenetic response; e19a2; micro bcr::abl1 transcript
    DOI:  https://doi.org/10.7759/cureus.83363
  2. Blood Neoplasia. 2024 Mar;1(1): 100001
    KIR3DL1-HLA-Bw status in CML is associated with achievement of TFR: the POKSTIC trial, a multicenter observational study.
    Hiroshi Ureshino, Yasunori Ueda, Shin Fujisawa, Kensuke Usuki, Hideo Tanaka, Masaya Okada, Shugo Kowata, Kazunori Murai, Asao Hirose, Motohiro Shindo, Takashi Kumagai, Tomoharu Takeoka, Kazuharu Kamachi, Keisuke Kidoguchi, Takero Shindo, Satoshi Iyama, Junki Inamura, Takafumi Nakao, Tsutomu Kobayashi, Eri Kawata, Hiroshi Ohkawara, Takayuki Ikezoe, Atsushi Kawaguchi, Shinya Kimura.
      Achievement of treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation in patients who show a durable deep molecular response (DMR) during TKI treatment of chronic myeloid leukemia in chronic phase (CML-CP) is a therapeutic goal; however, the prognostic factors that predict successful achievement of TFR are unclear. Previously, we reported that killer immunoglobulin-like receptor (KIR) and HLA polymorphisms are associated with achievement of a DMR. Here, we investigated the association between KIR and HLA polymorphisms and TFR. We conducted the POKSTIC (POlymorphisms of Killer immunoglobulin-like receptor, which affect Stop Tyrosine kinase Inhibitor in patients with Chronic myeloid leukemia) trial, a multicenter collaborative observational study that enrolled 76 patients with CML-CP. The median age was 63 years (interquartile range [IQR], 49-70). Of 76 patients, 42 (56.6%; 95% confidence interval [CI], 47.7-66.8 at 6 months) discontinued TKIs without molecular relapse; the median follow-up time for TFR was 24 months (IQR, 16-64). KIR genotyping and allele typing did not identify risk factors for molecular relapse; however, univariate and multivariate analysis identified the combination of KIR3DL1-HLA-Bw4 (an HLA-B allele) as an independent factor for a higher risk of molecular relapse (hazard ratio, 2.206; 95% CI, 1.112-4.376; P = .024). Notably, patients at higher risk of relapse had a significantly lower number of natural killer (NK) cells at TKI discontinuation than the other patients (CD16+/CD56+ NK cells: median 499.63 cells per μL vs 629.17 cells per μL, respectively; P = .049). Thus, KIR3DL1-HLA-Bw status reflects NK cell responses and is associated with TFR. The study is registered with the UMIN Clinical Trials Registry as #UMIN000041798.
    DOI:  https://doi.org/10.1016/j.bneo.2024.100001
  3. Blood Adv. 2025 Jun 05. pii: bloodadvances.2024015274. [Epub ahead of print]
    Indirect comparison of epcoritamab vs chemoimmunotherapy, mosunetuzumab, or odronextamab in follicular lymphoma.
    Alexey V Danilov, Swetha Thiruvengadam, Kim Linton, Karen Cumings, Viktor V Chirikov, Alex Mutebi, Savreet Bains Chawla, Anindit Chhibber, Fernando Rivas Navarro, Felipe Marques Gonçalves, Anthony Wang, Zhijie Ding, Abualbishr Alshreef, Elena Favaro, Daniela Hoehn, Anna Sureda.
      This matching-adjusted indirect comparison (MAIC) evaluated the efficacy of epcoritamab vs standard of care (SOC), mosunetuzumab, or odronextamab and assessed safety vs mosunetuzumab and odronextamab. Individual patient-level data from the EPCORE NHL-1 follicular lymphoma (FL) cohort for epcoritamab were used with pooled data from SCHOLAR-5 for SOC (mostly chemoimmunotherapy [CIT]), and aggregate data from GO29781 for mosunetuzumab and ELM-2 for odronextamab. Trial populations were match-adjusted using propensity score weights for key baseline characteristics. Compared with SOC/CIT, epcoritamab provided significantly higher response rates (overall response rate [ORR]: 90.9% vs 56.8%; P < .001; complete response [CR] rate: 73.7% vs 32.0%; P < .001). Epcoritamab showed numerically higher ORR (90.9% vs 80.0%; P = .067) and CR rate (72.8% vs 60.0%; P = .159) vs mosunetuzumab. Epcoritamab provided significantly higher ORR (91.5% vs 80.5%; P = .026) and numerically lower CR rate (67.5% vs 73.4%; P = .428) vs odronextamab. Epcoritamab did not have any grade ≥3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS; any grade) events compared with CRS (grade ≥3) in 2.2% and 3.9% and ICANS in 4.4% and 0.8% of patients treated with mosunetuzumab and odronextamab, respectively (P < .001). In addition to being a convenient subcutaneous option, epcoritamab showed significantly superior response rates and survival outcomes vs SOC/CIT among patients with relapsed or refractory FL after ≥2 systemic therapies. Epcoritamab also exhibited clinically relevant, numerically higher ORRs and demonstrated improved safety for CRS (grade ≥3) and ICANS vs mosunetuzumab or odronextamab. NCT03625037; NCT02500407; NCT03888105.
    DOI:  https://doi.org/10.1182/bloodadvances.2024015274
  4. N Engl J Med. 2025 Jun 03.
    Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma.
    MIDAS Study Group
       BACKGROUND: Measurable residual disease (MRD) is a major prognostic factor in newly diagnosed multiple myeloma. An assessment of an MRD-guided consolidation strategy in patients who are eligible for autologous stem-cell transplantation (ASCT) may be useful.
    METHODS: In this phase 3 trial, we randomly assigned transplantation-eligible patients with newly diagnosed myeloma who had completed induction therapy with isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) to receive consolidation therapy according to their MRD status. Patients who were MRD-negative at 10-5 sensitivity (i.e., <1 cancer cell per 100,000 normal cells, as assessed by next-generation sequencing were assigned to undergo ASCT and receive Isa-KRd for two cycles (ASCT group) or to receive Isa-KRd for six cycles (Isa-KRd group). Patients who were MRD-positive at 10-5 sensitivity were assigned to undergo tandem ASCT (two ASCTs within a short period; tandem ASCT group) or to undergo ASCT and receive Isa-KRd for two cycles (single ASCT group). The primary end point was an MRD-negative status at 10-6 sensitivity before maintenance therapy.
    RESULTS: Among 485 patients who were MRD-negative at 10-5 sensitivity after induction, a premaintenance MRD-negative status at 10-6 sensitivity occurred in 86% in the ASCT group and in 84% in the Isa-KRd group (adjusted relative risk, 1.02; 95% confidence interval [CI], 0.95 to 1.10; P = 0.64). Among 233 patients who were MRD-positive at 10-5 sensitivity after induction, a premaintenance MRD-negative status at 10-6 sensitivity occurred in 32% in the tandem ASCT group and in 40% in the single ASCT group (adjusted relative risk, 0.82; 95% CI, 0.58 to 1.15; P = 0.31); 15% of the patients in the tandem ASCT group did not undergo a second ASCT. During consolidation, disease progression occurred in 5 patients and death unrelated to disease progression occurred in 2 patients - all were in the Isa-KRd or tandem ASCT groups. No new safety signals were observed. The median follow-up was 16.8 months in the ASCT and Isa-KRd groups and 16.3 months in the tandem ASCT and single ASCT groups.
    CONCLUSIONS: Among patients who were MRD-negative at 10-5 sensitivity after induction, the percentage with a premaintenance MRD-negative status at 10-6 sensitivity was not significantly higher with ASCT than with Isa-KRd. Among patients who were MRD-positive status at 10-5 sensitivity after induction, the percentage with a premaintenance MRD-negative status at 10-6 sensitivity was not significantly higher with tandem ASCT than with single ASCT. (Funded by Intergroupe Francophone du Myélome and others; MIDAS ClinicalTrials.gov number, NCT04934475.).
    DOI:  https://doi.org/10.1056/NEJMoa2505133
  5. Blood Neoplasia. 2024 Jun;1(2): 100014
    CD302 predicts achievement of deep molecular response in patients with chronic myeloid leukemia treated with imatinib.
    Chung Hoow Kok, Yazad Irani, Jade Clarson, Verity Saunders, Phuong Dang, Naranie Shanmuganathan, Susan Branford, David Yeung, Agnes S M Yong, Timothy P Hughes.
      Achieving a deep molecular response (DMR) is a prerequisite for treatment-free remission in chronic myeloid leukemia (CML) and a key milestone for patients with CML. This study identified patients unlikely to achieve a 5-year DMR through differential expression of cluster of differentiation (CD) genes, and clinical variables at diagnosis. Peripheral blood samples (n = 131) from patients treated with imatinib or nilotinib underwent transcriptomic microarray profiling. The decision-tree analysis delineated 2 distinct poor-risk (PR) cohorts, distinguished by high 3-month BCR::ABL1% (PR-1), or high CD302 expression (PR-2). The 5-years DMR achievement rate was significantly lower in both PR groups than in the good-risk (GR) group in patients treated frontline with imatinib (0% vs 27% vs 83%; P < .0001) or nilotinib (PR-2 vs GR, 17% vs 83%; P = .02). Gene-set enrichment analysis revealed reduced expression of cell cycle-related genes in PR-2, as well as increased metabolism and STAT3 pathway genes, which has previously been linked to leukemic cell persistence and resistance to tyrosine kinase inhibitors. Moreover, PR-2 had a higher frequency of CD34+CD302+ and CD14+CD302+ cells than GR samples. Strategies aimed at targeting STAT3 and/or metabolic pathways associated with high CD302 may provide novel therapeutic approaches that could help improve treatment outcomes and eradicate residual disease.
    DOI:  https://doi.org/10.1016/j.bneo.2024.100014
  6. Am J Hematol. 2025 Jun 05.
    Outcome of Chronic Myeloid Leukemia Patients Not in Deep Molecular Response: Results From the GIMEMA LabNet CML Network Database.
    Fabio Stagno, Rosalba Cucci, Giovanni Marsili, Fausto Castagnetti, Sara Galimberti, Barbara Izzo, Federica Sorà, Simona Soverini, Monica Messina, Alfonso Piciocchi, Massimiliano Bonifacio, Daniela Cilloni, Alessandra Iurlo, Giovanni Martinelli, Gianantonio Rosti, Paola Fazi, Marco Vignetti, Massimo Breccia, Alessandro Allegra, Fabrizio Pane.
      
    DOI:  https://doi.org/10.1002/ajh.27733
  7. Rinsho Ketsueki. 2025 ;66(5): 324-330
    [Drug-induced sarcoidosis-like reaction due to dasatinib in the lung of a patient with chronic myeloid leukemia].
    Takumi Kimura, Yoshimi Nabe, Hiroki Yoshino, Ryota Urushihara, Noriaki Tsuji, Yukio Kondo.
      The patient was a 54-year-old woman with chronic myeloid leukemia. Ten months after treatment with dasatinib, she developed a cough. Imaging studies showed ground-glass patterns in the lower lung fields of both lungs, which led to suspicion of drug-induced lung injury and prompted discontinuation of dasatinib. A transbronchial lung biopsy showed epithelioid granuloma without necrosis in the alveolar region. There were no other systemic symptoms or signs to support a diagnosis of sarcoidosis. Fifteen days after withdrawal of dasatinib, both the cough and X-ray findings improved. Granulomatous tissue was detected on lung biopsy, which indicates that drug-induced sarcoidosis-like reaction (DISR) may cause interstitial lung injury as a respiratory complication of dasatinib treatment. Case reports of DISR following administration of immune checkpoint inhibitors and immunomodulatory drugs have recently become more frequent. Here we report a case of dasatinib-induced DISR with a review of the literature.
    Keywords:  Chronic myeloid leukemia; Dasatinib; Drug-induced sarcoidosis-like reaction
    DOI:  https://doi.org/10.11406/rinketsu.66.324
  8. Ann Hematol. 2025 Jun 05.
    Ixazomib-lenalidomid-dexamethasone (IRd) in relapsed refractory multiple myeloma (RRMM)-multicenter real-world analysis from Germany and comparative review of the literature.
    Hanna Löffler, Magdalena Braun, Heike Reinhardt, Amelie Rösner, Gabriele Ihorst, Jan Räder, Sina Wenger, Annamaria Brioli, Marie von Lilienfeld-Toal, Maika Klaiber-Hakimi, Eva-Marie Fehr, Markus Munder, Katharina Epp, Karolin Trautmann-Grill, Sarah Decker, Holger Hoff, Ralph Wäsch, Monika Engelhardt.
      With the introduction of novel agents (proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), immuntherapeutics), the outcome of multiple myeloma (MM) patients has improved. The oral PI ixazomib was authorized in the EU in 11/2016 and is indicated in combination with lenalidomide and dexamethasone (IRd) for the treatment of patients with relapsed/refractory MM (RRMM). The study aim was to identify the typical real world (RW) RRMM patient population in Germany treated with IRd and to compare the outcome to prior IRd cohorts. Our retrospective study included consecutive RRMM patients receiving IRd in six large German hospitals between 06/2017 and 12/2021. We identified 24 consecutive RRMM patients within these six institutions. Their median age was 68 years at the start of IRd; 21% carrying high-risk cytogenetics [del17p, t(4;14) and/or t(14;16)]. Patients had a median of 2 prior treatment lines (range, 1-5), prior PI/IMiD exposure was 100%/58%, comparable to previous real world evidence (RWE)-studies. With a median follow-up of 37.7 months, the overall response rate was 70.8%, and median PFS and OS were 22.0 and 62.2 months, respectively. With these German data, our study is closing an important gap of IRd real world data (RWD) reporting across Europe, providing median PFS/OS data and comparison to prior IRd studies. IRd is a well-tolerated and effective triplet regimen, often given as 2nd or 3rd-line therapy in RRMM, with results confirming the registration trial and other international RW-analyses.
    Keywords:  German RRMM patients; Ixazomib-lenalidomide-dexamethasone (IRd); Multiple Myeloma (MM); Real Word Evidence (RWE); Real world data (RWD); Relapsed/refractory (RR)
    DOI:  https://doi.org/10.1007/s00277-025-06441-8
  9. J Clin Oncol. 2025 Jun 06. JCO2500166
    Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor-Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321).
    Jeff P Sharman, Talha Munir, Sebastian Grosicki, Lindsey E Roeker, John M Burke, Christine I Chen, Norbert Grzasko, George Follows, Zoltán Mátrai, Alessandro Sanna, Lugui Qiu, Ru Feng, Vu Minh Hua, Wojciech Jurczak, Matthias Ritgen, Shuhua Yi, Francesc Bosch, Catherine C Coombs, Katherine Bao, Vishalkumar Patel, Bin Liu, Livia Compte, Ananya Guntur, Denise Y Wang, Marisa Hill, Ching Ching Leow, Paolo Ghia, Paul M Barr.
       PURPOSE: Pirtobrutinib, a noncovalent, Bruton tyrosine kinase inhibitor (BTKi), has shown clinical efficacy and a favorable safety profile. BRUIN CLL-321 was an open-label, randomized phase III study conducted exclusively in patients with R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) previously treated with cBTKi, and compared pirtobrutinib with investigator's choice (IC) of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BR).
    METHODS: Patients were randomly assigned 1:1 to receive pirtobrutinib (200 mg once daily) or IC of IdelaR or BR, and were stratified by previous use of venetoclax and del(17p). The primary end point was independent review committee-assessed progression-free survival (PFS). Secondary end points included time to next treatment or death (TTNT), overall survival (OS), and safety. The primary PFS end point was met at the time of the primary analysis (August 29, 2023), and updated results are reported from the final OS analysis (August 29, 2024).
    RESULTS: A total of 238 patients were randomly assigned to receive pirtobrutinib (n = 119) or IC (n = 119; IdelaR [n = 82], BR [n = 37]). The PFS hazard ratio (HR) was 0.54 ([95% CI, 0.39 to 0.75]; P = .0002), with a median PFS of 14 months (95% CI, 11.2 to 16.6) in the pirtobrutinib group and 8.7 months (95% CI, 8.1 to 10.4) with IC. The unadjusted OS HR was 1.09 ([95% CI, 0.68 to 1.75]; P = .7202), and 18-month OS rate was 73.4% (95% CI, 63.9 to 80.7) in the pirtobrutinib group and 70.8% (95% CI, 60.9 to 78.7) with IC. Median TTNT was 24 months (95% CI, 17.8 to 29.7) with pirtobrutinib versus 10.9 months (95% CI, 8.7 to 12.5) with IC (HR, 0.37 [95% CI, 0.25 to 0.52]). At a median follow-up of 17.2 months, grade ≥3 treatment-emergent adverse events (AEs) were lower with pirtobrutinib (57.7%) than IC (73.4%). Treatment discontinuation due to AE occurred in 20 (17.2%) patients receiving pirtobrutinib and 38 (34.9%) patients receiving IC.
    CONCLUSION: Pirtobrutinib improved PFS and TTNT, and demonstrated favorable tolerability, versus IdelaR/BR in exclusively cBTKi pretreated patients with CLL/SLL.
    DOI:  https://doi.org/10.1200/JCO-25-00166
  10. Front Immunol. 2025 ;16 1579483
    Clinical outcomes of newly diagnosed PCNSL treated with rituximab-methotrexate-cytarabine with or without ibrutinib: a retrospective study.
    Wenhua Wang, Bingyi Wang, Yifei Sun, Lihua Qiu, Zhengzi Qian, Shiyong Zhou, Zheng Song, Wei Li, Lanfang Li, Xianhuo Wang, Huilai Zhang.
       Objective: This study aimed to evaluate the efficacy and safety of rituximab, methotrexate, cytarabine with or without ibrutinib in newly diagnosed primary central nervous system lymphoma (PCNSL) and explore the correlation between efficacy and genomic alterations.
    Methods: From March 2013 to October 2022, data from 88 patients with newly diagnosed PCNSL were retrospectively collected and analyzed. Fifty-nine patients received rituximab, methotrexate and cytarabine (RMA, group A), and twenty-nine patients received the same RMA combined with ibrutinib (RMA + Ibrutinib, group B).
    Results: At a median follow-up of 27.7 months, the complete response rate (CRR), overall response rate (ORR) and overall survival (OS) in group B superior to group A (41.4% versus 16.9% for CRR, P=0.013; 86.2% versus 59.3% for ORR, P=0.011; P=0.036 for OS). The ORR, progression-free survival (PFS) and OS of RMA + ibrutinib +deep lesions (group C) were better than those of RMA + deep lesions (group D) (P=0.027 for ORR, P=0.046 for PFS, P=0.004 for OS). Patients in group B had no more toxicities than those in group A and the most common adverse events in the two groups were primarily grade 1-2. Sequencing of tumor tissues from 22 patients showed that MYD88 mutations were the most frequent genetic alterations, two patients with CARD11 mutation did not respond to treatment and three patients without an MYD88 or CD79B had response after treatment.
    Conclusions: RMA in combination with ibrutinib regimen improved response rates and survival in newly diagnosed PCNSL with no serious adverse effects. Mutations in CARD11 gene may provide directions for patients to select targeted drugs.
    Keywords:  central nervous system; ibrutinib; lymphoma; methotrexate; retrospective
    DOI:  https://doi.org/10.3389/fimmu.2025.1579483
  11. Clin Pharmacol. 2025 ;17 97-117
    Novel Therapies in Primary Central Nervous System Lymphoma.
    Michel Wakim, Mariana Mezher, Ariel Perez-Perez, Arun Maharaj, Yazmin Odia, Manmeet S Ahluwalia, Yuliya Linhares.
      Primary central nervous system lymphoma (PCNSL) is a rare, aggressive, extranodal lymphoma exclusively located in the central nervous system. High-dose methotrexate (HD-MTX)-based chemotherapy combination regimens are now the standard of care for the upfront treatment of PCNSL and are used in a salvage setting but are toxic and cumbersome to administer because of the need for inpatient supportive care. While the incidence of PCNSL is increasing in the aging population, a significant proportion of patients are unable to follow HD-MTX protocols owing to performance status and organ dysfunction. Consolidative autologous stem cell transplant or whole-brain radiation therapy improves progression-free survival at the cost of short- and long-term toxicities. Induction of low toxicity and consolidative and salvage therapeutic options are lacking. Due to its unique biology, PCNSL presents an exciting opportunity for the development of novel therapies with improved efficacy and toxicity. In this review, we focus on the biology of PCNSL and novel chemotherapeutics, including targeted and immunotherapeutic agents as well as cellular therapies. Expert Opinion summary: Given the lack of low-toxicity standard treatments for PCNSL, the outcomes for aging PCNSL patients remain suboptimal. Current research has focused on introducing targeted immunotherapies into the induction, salvage, and consolidation treatments of PCNSL.
    Keywords:  Bruton tyrosine kinase (BTK) signaling pathway in PCNSL; chimeric antigen receptor T cells (CARTs) in PCNSL; high-dose methotrexate (HD-MTX) in PCNSL; immunotherapy in PCNSL; primary central nervous system lymphoma (PCNSL); targeted therapy in PCNSL
    DOI:  https://doi.org/10.2147/CPAA.S501065
  12. J Clin Oncol. 2025 May 31. JCO2500758
    Zanubrutinib and Venetoclax for Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With and Without Del(17p)/TP53 Mutation: SEQUOIA Arm D Results.
    Mazyar Shadman, Talha Munir, Shuo Ma, Masa Lasica, Monica Tani, Tadeusz Robak, Ian W Flinn, Jennifer R Brown, Paolo Ghia, Emmanuelle Ferrant, Constantine S Tam, Wojciech Janowski, Wojciech Jurczak, Linlin Xu, Tian Tian, Marcus Lefebure, Stephanie Agresti, Jamie Hirata, Alessandra Tedeschi.
       PURPOSE: Several chronic lymphocytic leukemia (CLL) studies have demonstrated promising efficacy with the combination of BCL2 and Bruton tyrosine kinase inhibitors; however, patients with CLL with del(17p) and/or TP53 mutation (TP53mut) comprised a small percentage of study populations or were excluded entirely. The purpose of the SEQUOIA Arm D cohort was to evaluate the combination of zanubrutinib + venetoclax in treatment-naïve (TN) patients with CLL/small lymphocytic lymphoma (SLL), in a large population of patients with TP53-aberrant disease.
    PATIENTS AND METHODS: Arm D is a nonrandomized cohort of patients aged 65 years and older (or 18-64 years with comorbidities). Patients received zanubrutinib from cycle 1 and venetoclax from cycle 4 (ramp-up) to cycle 28, followed by continuous zanubrutinib monotherapy until progressive disease (PD), unacceptable toxicity, or meeting undetectable minimal residual disease (uMRD)-guided stopping criteria.
    RESULTS: Between November 2019 and July 2022, 114 patients were enrolled: 66 (58%) with TP53-aberrant disease, 47 (41%) without TP53-aberrant disease, and 1 with missing TP53 results. At a median follow-up of 31.2 months, 85 patients (75%) remained on zanubrutinib monotherapy; 29 patients (25%) discontinued zanubrutinib because of adverse event, uMRD-guided stopping criteria, PD, or other. In the intention-to-treat population, 59% of patients achieved peripheral blood uMRD. The 24-month progression-free survival estimate was 92% (95% CI, 85% to 96%). The most common any-grade treatment-emergent AEs (TEAEs) were COVID-19 (54%), diarrhea (41%), contusion (32%), and nausea (30%). The most common grade ≥3 TEAEs were neutropenia (17%), hypertension (10%), diarrhea (6%), and decreased neutrophil count (6%).
    CONCLUSION: Zanubrutinib + venetoclax demonstrated impressive efficacy and a favorable safety profile in patients with TN CLL/SLL, regardless of the presence of TP53-aberrant disease.
    DOI:  https://doi.org/10.1200/JCO-25-00758
  13. J Clin Oncol. 2025 Jun 03. JCO2500760
    Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma.
    Sundar Jagannath, Thomas G Martin, Yi Lin, Adam D Cohen, Noopur Raje, Myo Htut, Abhinav Deol, Mounzer Agha, Jesus G Berdeja, Alexander M Lesokhin, Jessica J Liegel, Adriana Rossi, Alex Lieberman-Cribbin, Saad Z Usmani, Binod Dhakal, Samir Parekh, Hui Li, Feng Wang, Rocio Montes de Oca, Vicki Plaks, Huabin Sun, Arnob Banerjee, Jordan M Schecter, Nikoletta Lendvai, Deepu Madduri, Tamar Lengil, Jieqing Zhu, Mythili Koneru, Muhammad Akram, Nitin Patel, Octavio Costa Filho, Andrzej J Jakubowiak, Peter M Voorhees.
      CARTITUDE-1 evaluated ciltacabtagene autoleucel (cilta-cel) in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). We describe overall survival (OS), ≥5-year progression-free outcomes, associated biomarkers, and safety, with a median study follow-up of 61.3 months. For the 97 treated patients, median OS was 60.7 months (95% CI, 41.9 to not estimable). One third (32/97) of patients remain alive and progression-free for ≥5 years after a single cilta-cel infusion, without maintenance treatment. Twelve of these patients treated at a single center underwent serial minimal residual disease (MRD) and positron emission tomography-computed tomography assessments, and all (100%) were MRD-negative (at least 10-5 threshold) and imaging-negative at year 5 or later after cilta-cel. Baseline characteristics, including the presence of high-risk cytogenetics and extramedullary disease, were generally comparable for the 32 patients who were progression-free for ≥5 years versus patients who had progressive disease by year 5. A trend of lower baseline tumor burden, higher fraction of naïve T-cells in the cilta-cel drug product, higher T cell-to-neutrophil ratio, higher hemoglobin and platelets at baseline, and higher effector-to-target ratio were associated with ≥5-year progression-free status. The safety profile of cilta-cel remained consistent with previous reports. To our knowledge, our data provide the first evidence that cilta-cel is potentially curative in patients with RRMM.
    DOI:  https://doi.org/10.1200/JCO-25-00760
  14. Front Pharmacol. 2025 ;16 1585061
    Investigation of the mechanism of hypertension caused by BTKi in the treatment of hematologic diseases.
    Jiayi Xu, Junling Lin, Haojian Gan, Qingjian He, WenJuan Wang, Yuanhua Liu.
      Bruton's tyrosine kinase inhibitors (BTKis) have made substantial impacts on the treatment of B-cell malignancies like chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Therapeutic benefits aside, the clinical use of BTKis comes with several side effects, of which hypertension (HTN) is quite common and serious and of significant clinical concern. The present article will discuss the mechanisms by which the use of BTKis causes hypertension and outline strategies for managing the condition within the clinic. Studies indicate that using BTKis interferes with BTK's central role within the B-cell receptor (BCR) signaling cascade and impacts multiple downstream signaling pathways like PI3K/Akt, MAPK, and NF-κB. These changes contribute to endothelial dysfunction, increased oxidative stress, and vascular constriction, all of which are implicated in the development of hypertension. Of special concern is that oxidative stress (OS) is directly related to decreased endothelial nitric oxide (NO) production, a finding that becomes particularly relevant during the initiation of BTKi therapy. Also, BTKis affect vascular development and tone regulation by activating the Notch and RhoA/ROCK pathways, leading to increased vasoconstriction and the advancement of hypertension. In light of the possibility that BTKi-induced hypertension might jeopardize treatment tolerability and patient outcomes, this review proposes a multimodal management of the condition, including careful monitoring of blood pressure, individualized antihypertensive treatment, and possible modifications of the dosing of BTKis. Future investigations should look into the specific molecular mechanisms underpinning the development of hypertension due to BTKis as well as the effects of various antihypertensive regimens on the improvement of the cardiovascular profile of affected individuals.
    Keywords:  BTKi; cardiovascular diseases; hypertension; ibrutinib; oxidative stress
    DOI:  https://doi.org/10.3389/fphar.2025.1585061
  15. Future Oncol. 2025 Jun 06. 1-9
    Indirect treatment comparisons of momelotinib vs pacritinib safety and anemia outcomes in patients with myelofibrosis.
    Lucia Masarova, Srdan Verstovsek, Francesca Palandri, Ruben Mesa, Claire Harrison, Balázs Dobi, Boris Gorsh, Zhaohui Wang, Catherine Ellis, Dwaipayan Patnaik, Tom Liu, Venediktos Kapetanakis.
       AIM: To perform an indirect treatment comparison of safety and anemia outcomes between the Janus kinase (JAK) inhibitors momelotinib and pacritinib in patients with myelofibrosis.
    METHODS: Treatment-emergent adverse events (AEs) and anemia outcomes were compared in a pooled population of JAK inhibitor - experienced and - naive patients treated with momelotinib (SIMPLIFY-1/SIMPLIFY-2/MOMENTUM) or pacritinib (PERSIST-2/PAC203).
    RESULTS: Momelotinib had statistically significantly lower odds and risk for all grades of diarrhea, nausea, peripheral edema, and vomiting as well as grade 3/4 and serious AEs vs pacritinib. Momelotinib-treated patients also had greater odds/possibility of hemoglobin improvement of ≥ 1 g/dL and clinical improvement in hemoglobin.
    CONCLUSIONS: Momelotinib provides a more favorable safety profile and a higher chance for hemoglobin improvement vs pacritinib.
    Keywords:  JAK inhibitor; Myelofibrosis; indirect treatment comparison; momelotinib; pacritinib; safety
    DOI:  https://doi.org/10.1080/14796694.2025.2511562
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