bims-hemali Biomed News
on Hematologic malignancies
Issue of 2026–08–16
twelve papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Venetoclax plus azacitidine, low-dose cytarabine, aclarubicin, and G-CSF (VA-CAG regimen) for newly diagnosed young patients with acute myeloid leukemia: A prospective, multicenter, single-arm Phase II clinical trial.
  2. Matching-adjusted indirect comparison between asciminib and flumatinib as first-line treatment for chronic myeloid leukemia in China.
  3. Do FLT3 and KIR3DL1 converge on a common immune surveillance axis in treatment-free remission of chronic myeloid leukemia?
  4. Peripheral neuropathies associated with immunoglobulin M monoclonal gammopathies and low-grade B-cell lymphomas: diagnostic and therapeutic approach.
  5. Real-World Treatment Patterns for Waldenstrom Macroglobulinemia: Implications for Treatment Sequencing.
  6. Glofitamab-Based Therapy for Relapsed or Refractory CNS Lymphoma: A Multicenter Retrospective Study.
  7. IKAROS descent and rise of lenalidomide-associated B-ALL.
  8. Long-term extended-interval teclistamab and talquetamab dosing without step-up dosing in previously treated multiple myeloma.
  9. Sequential therapy with decitabine and an XPO-1 inhibitor followed by allogeneic hematopoietic stem cell transplantation in MDS with biallelic TP53 inactivation patients : a preliminary case series.
  10. A53-Adapted Decitabine-Containing R-CHOP in Newly Diagnosed Diffuse Large B-Cell Lymphoma Defined by LymphGen: Preliminary Results of a Prospective Proof-of-Concept Study.
  11. Quizartinib Resistance Mutations and Treatment Outcomes in Relapsed or Refractory FLT3-ITD-Positive AML.
  12. FLT3-ITD MRD is here to stay.
  1. Hemasphere. 2026 Aug;10(8): e70449
    Venetoclax plus azacitidine, low-dose cytarabine, aclarubicin, and G-CSF (VA-CAG regimen) for newly diagnosed young patients with acute myeloid leukemia: A prospective, multicenter, single-arm Phase II clinical trial.
    Xiaoping Li, Qiurong Zhang, Xiaoyan Li, Lin Liu, Yonglin Shen, Yu Li, Lihui Peng, Chaoyang Zhou, Chie Qiu, Zhongtao Yuan, Shiqian Hou, Youcheng Wang, Lihua Zhang, Jingqiong Li, Liang Zhao, Qiuyuan Tang, Zucong Chen, Jing Feng, Xuejuan Zhang, Guoxiu Bao, Kui Zhang, Renpeng Zhang, Shiqi Li, Yingnian Chen, Jianhua Rao, Yancheng Dong, Dingsong Zhang, Yueyuan Wang, Aifang Li, Xi Ye, Lei Lei, Jiao Chen, Sufen Xu, Yanling Jin, Chaoen Zheng, Yang Liang, Sanbin Wang.
      We conducted a prospective, multicenter, Phase II study to evaluate the safety and efficacy of venetoclax/azacitidine/low-dose cytarabine/aclarubicin/granulocyte colony-stimulating factor (G-CSF) (VA-CAG) in young patients with newly diagnosed acute myeloid leukemia (ND-AML). The VA-CAG regimen included venetoclax (100 mg/day, Days 1-2; 200 mg, Day 3; 400 mg/day, Days 4-21), azacitidine (75 mg/m2, Days 1-7), cytarabine (10 mg/m2/12 h, Days 1-7), aclarubicin (12 mg/m2, Days 1, 3, 5, and 7), and G-CSF (5 μg/kg/day, Days 0-8). The primary endpoint was the complete remission (CR) rate after Cycle 1; the secondary endpoints included measurable residual disease (MRD)-negative remission rate, adverse events, and duration of remission (DOR). A total of 120 subjects were enrolled. The median age was 50 years (interquartile range, IQR, 36-57). The CR and composite complete response (CRc) rates were 91% (95% CI 86%-96%) and 95% (95% CI 91%-99%), respectively; 84% (95% CI 81%-88%) of the CRc patients achieved MRD-negative remission. Common Grade ≥4 adverse events included neutropenia (96%), thrombocytopenia (86%), febrile neutropenia (24%), pneumonia (4%), and sepsis (4%). The median times to recovery of absolute neutrophil count (ANC) ≥ 0.5 × 109/L and platelet count ≥ 20 × 109/L for responding patients were 14 days (IQR, 9-19) and 10 days (IQR, 4-16), and the 60-day mortality rate was 0%. With a median follow-up of 22.1 months (95% CI 20.4-23.7 months), 34 subjects subsequently received hematopoietic stem cell transplantation (HSCT). The median DOR values of all patients and the patients who did not receive HSCT were not reached. Hence, the VA-CAG regimen is a safe and effective first-line induction chemotherapy for ND-AML patients.
    DOI:  https://doi.org/10.1002/hem3.70449
  2. Transl Cancer Res. 2026 Jul 31. 15(7): 565
    Matching-adjusted indirect comparison between asciminib and flumatinib as first-line treatment for chronic myeloid leukemia in China.
    Ying Wang, Yan Hui, Li Zhang, Yan Li, Meng Tang, Xue Gao, Bihong Zhen, Abhay Choubey, Soni Gupta, Hui Wei, Bingcheng Liu.
       Background: Asciminib, a novel BCR::ABL1 inhibitor that functions by specifically targeting the myristoyl pocket, has shown superior efficacy and favorable safety and tolerability compared with adenosine triphosphate-competitive tyrosine kinase inhibitors (TKIs) in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Flumatinib, a second-generation TKI available exclusively in China, does not have a head‑to‑head comparison with asciminib till date with asciminib. Therefore, this study aimed to conduct an anchored matching‑adjusted indirect comparison using data from the ASC4FIRST and FESTnd trials to fill this evidence gap.
    Methods: Imatinib was the common comparator across the ASC4FIRST (NCT04971226) and FESTnd (NCT02204644) trials. To match the two populations, effect modifiers and baseline variables were identified. Adjusted estimates were derived from individual patient-level data (ASC4FIRST) for asciminib and imatinib and from aggregate data for flumatinib (FESTnd). Outcomes were compared based on early molecular response (EMR), major molecular response (MMR), and treatment discontinuation due to adverse events (AEs).
    Results: Asciminib demonstrated significantly higher EMR rates at 12 weeks (adjusted: 90.0%) than did flumatinib (82.1%), yielding a significantly higher odds ratio [odds ratio (OR): 1.95; 95% confidence interval (CI): 1.05-3.73; P=0.03]. MMR rates, both at 48 and 96 weeks, were significantly higher for asciminib (adjusted: 66.5% and 74.0%, respectively) than for flumatinib (an estimated 52.6% and 61.3%, respectively), with an OR of 1.79 (95% CI: 1.17-2.75; P=0.006). Safety analysis showed fewer discontinuations due to AEs at 48 weeks with asciminib (5.5%) than with flumatinib (10.2%), corresponding to a significantly lower risk of discontinuation due AEs (risk ratio: 0.29; 95% CI: 0.10-0.84; P=0.02).
    Conclusions: A robust statistical model indicated that asciminib provides consistently superior efficacy and safety over flumatinib, supporting its value as a first-line treatment option for patients with CML-CP.
    Keywords:  Chronic myeloid leukemia (CML); efficacy; matching-adjusted indirect comparison (MAIC); safety; tyrosine kinase inhibitors (TKIs)
    DOI:  https://doi.org/10.21037/tcr-2026-1659
  3. Leukemia. 2026 Aug 12.
    Do FLT3 and KIR3DL1 converge on a common immune surveillance axis in treatment-free remission of chronic myeloid leukemia?
    Mai Fujita, Hiroshi Ureshino.
      
    DOI:  https://doi.org/10.1038/s41375-026-03113-y
  4. Curr Opin Oncol. 2026 Sep 01. 38(5): 374-381
    Peripheral neuropathies associated with immunoglobulin M monoclonal gammopathies and low-grade B-cell lymphomas: diagnostic and therapeutic approach.
    Damien Roos-Weil.
       PURPOSE OF REVIEW: Peripheral neuropathies associated with monoclonal gammopathies and low-grade B-cell lymphomas represent a clinically heterogeneous group of disorders encountered by both neurologists and hematologists. This review provides a practical and updated approach to their diagnosis and management, with a particular focus on IgM-associated neuropathies and anti-MAG neuropathy.
    RECENT FINDINGS: IgM-related neuropathies encompass immune-mediated disorders - most commonly driven by antibodies against myelin-associated glycoprotein (MAG) - as well as infiltrative mechanisms (neurolymphomatosis, Bing-Neel syndrome) and protein deposition diseases (AL amyloidosis). Anti-MAG neuropathy remains the most common and best-characterized entity. Over the past decade, therapeutic strategies have evolved substantially with the emergence of clone-directed approaches, including anti-CD20-based regimens and covalent Bruton tyrosine kinase inhibitors (cBTKi). However, high-quality evidence remains limited.
    SUMMARY: Establishing a causal relationship between neuropathy and IgM gammopathy is essential and requires a multidisciplinary approach. Treatment should be individualized and primarily reserved for progressive, functionally impairing disease. Despite therapeutic advances, many patients experience persistent disability, underscoring the need for novel strategies and prospective clinical trials using validated neurological endpoints.
    Keywords:  Waldenström macroglobulinemia; anti-myelin-associated glycoprotein neuropathy; demyelinating neuropathy; immunoglobulin M monoclonal gammopathy; rituximab
    DOI:  https://doi.org/10.1097/CCO.0000000000001260
  5. J Korean Med Sci. 2026 Aug 10. 41(31): e206
    Real-World Treatment Patterns for Waldenstrom Macroglobulinemia: Implications for Treatment Sequencing.
    Seo Yoon Jang, Ja Min Byun, Sung-Soo Park, Youngju Kim, Jeongmin Park, Dong-Yeop Shin, Youngil Koh, Inho Kim, Chang Ki Min, Sung-Soo Yoon.
       BACKGROUND: Due to the rarity of Waldenstrom macroglobulinemia (WM) and scarcity of direct comparative data, there remains uncertainty regarding the optimal therapeutic approach for treatment-naïve patients and subsequent treatment sequence. To bridge such knowledge gap and generate data on most appropriate treatment in relatively resource constraint setting, we conducted this study with 168 WM patients.
    METHODS: Due to the diversity of treatment regimens, patients were categorized into four groups: cytotoxic regimen, rituximab-based regimen, proteasome inhibitor (PI)/immunomodulatory drug (IMiD)-based regimen, and bruton tyrosine kinase inhibitor (BTKi). Treatment patterns and efficacy outcomes were analyzed.
    RESULTS: The overall response rate (ORR) between rituximab-based vs. PI/IMiD based regimens were similar (74.2% vs. 80.0%, P = 0.750), but rituximab-based regimens were associated with longer response (median progression free survival [PFS] 44.3 vs. 8.5 months, P < 0.001), while PI/IMiD based regimens were associated with faster response (median time to initial response 1.8 vs. 0.9 months, P = 0.040). Among rituximab-based regimens, bendamustine-rituximab was associated with better response (ORR, 83.3%) and significantly longer PFS compared to rituximab + cyclophosphamide-based regimen group (median PFS 61.3 months vs. 18.2 months, P < 0.001). Ultimately 56% underwent second line treatment. Prior treatment did not seem to affect subsequent BTKi efficacy.
    CONCLUSION: Our findings underscore the importance of optimizing treatment strategies and offer real-world data to support informed decision-making in settings with constrained resources.
    Keywords:  Immunomodulatory Drugs; Proteasome Inhibitors; Rituximab; Waldenstrom Macroglobulinemia
    DOI:  https://doi.org/10.3346/jkms.2026.41.e206
  6. Blood Cancer Discov. 2026 Aug 11.
    Glofitamab-Based Therapy for Relapsed or Refractory CNS Lymphoma: A Multicenter Retrospective Study.
    Ruixian Xing, Apeng Yang, Juan Huang, Liang Wang, Wei Guo, Qu Cui, Xiaoqiong Tang, Yuanyuan Ma, Kai Hu, Tianheng He, Danyang Wu, Xiaofang Deng, Yajing Zhang, Kaili Zhong, Yang Liu, Yixian Guo, Ying Wang, Chan Long, Chongyang Wu, Xin Lu, Fengmin Li, Jiefei Bai, Jun Qian, Xuefei Sun, Wenrong Huang, Hui Zhou, Huilai Zhang, Ou Bai, Xiaobing Huang, Zhiyong Zeng, Lin Fu.
      Relapsed or refractory CNS lymphoma (R/R CNSL) has limited treatment options. This multicenter retrospective study enrolled 84 consecutive R/R CNSL patients (median age 59 years; 53 PCNSL, 31 SCNSL) to evaluate efficacy and safety profiles of glofitamab therapy. With a median of 2.5 prior lines of therapy, the objective response rates (ORR) and complete response rates (CRR) for PCNSL were 88% (CRR 59%) with glofitamab monotherapy (n=32) and 100% (CRR 81%) with combination therapy (n=21), respectively; for SCNSL, ORR and CRR were 88% (CRR 75%) with glofitamab monotherapy (n=8) and 91% (CRR 65%) with combination therapy (n=23). At 14.7 months follow-up, median progression-free survival was 19.5 months for PCNSL and 13.5 months for SCNSL. Cytokine release syndrome occurred in 40% (all grade 1-2) of patients, and ICANS in 8%. Glofitamab-based therapy demonstrated substantial activity with manageable toxicity in this study, offering a promising treatment paradigm for R/R CNSL patients.
    DOI:  https://doi.org/10.1158/2643-3230.BCD-26-0128
  7. Blood. 2026 Aug 13. 148(7): 800-801
    IKAROS descent and rise of lenalidomide-associated B-ALL.
    Benjamin Diamond.
      
    DOI:  https://doi.org/10.1182/blood.2026033360
  8. Exp Hematol Oncol. 2026 Aug 12. pii: 77. [Epub ahead of print]15(1):
    Long-term extended-interval teclistamab and talquetamab dosing without step-up dosing in previously treated multiple myeloma.
    Callee Brooks, Leslie Mader, Kathryn Kennedy, Phyu Thin Naing, Salyka Sengsayadeth, Bhagirathbhai Dholaria, Adetola Kassim, Sarah Profitt, Muhamed Baljevic.
      Teclistamab (Tec) and talquetamab (Tal) are bispecific CD3 T-cell engagers targeting B-cell maturation antigen and G protein-coupled receptor, class C, group 5, member D, respectively, and have transformed how we treat relapsed/refractory multiple myeloma (RRMM). Early onset toxicities, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), require utilization of pre-medications, step-up dosing (SUD) schemas, and close monitoring while late onset toxicities, such as hypogammaglobulinemia, myelosuppression, and notably infections, can lead to significant complications and treatment interruptions, which may require extending bispecific antibody (BsAb) dosing intervals to mitigate toxicities. While current prescribing information for Tec and Tal recommend repeat SUD for prolonged dose delays, we report a series of six patients (pts) who continued therapy with extended dosing intervals (EDI) (8-12 weeks) without repeating SUD. Notably, all pts had achieved a  ≥  complete response (CR) prior to transitioning to extended interval dosing, which was chosen either to improve tolerability or per provider preference based on depth of disease response. Despite experiencing CRS (83% of pts) and ICANS (17% of pts) during their initial SUD, no CRS or ICANS events occurred after 23 doses of Tec/Tal given at EDI, despite a median duration between doses of 77 days. At the time of this report, all patients in this cohort have sustained, deep disease response and remain on BsAb therapy. Despite small sample size, this report adds to limited available data supporting safe and feasible omission of SUD in RRMM pts slated for Tec/Tal therapy resumption via EDI.
    Keywords:  Extended-dosing; Multiple myeloma; Step-up dosing; Talquetamab; Teclistamab
    DOI:  https://doi.org/10.1186/s40164-026-00816-x
  9. Exp Hematol Oncol. 2026 Aug 10. pii: 76. [Epub ahead of print]15(1):
    Sequential therapy with decitabine and an XPO-1 inhibitor followed by allogeneic hematopoietic stem cell transplantation in MDS with biallelic TP53 inactivation patients : a preliminary case series.
    Yanling Ren, Wei Lang, Yu Xu, Chen Mei, Xianbo Huang, Shasha Wang, Jiejing Qian, Hongyan Tong.
      Myelodysplastic syndrome with biallelic TP53 inactivation (MDS-biTP53) patients represents an ultra-high-risk subgroup with dismal outcomes. Even after allogeneic hematopoietic stem cell transplantation (allo-HSCT), relapse rates remain extremely high and survival is poor. This preliminary case series reports the outcomes of 8 consecutive patients with MDS-biTP53 who received a novel sequential therapy of decitabine (DAC) combined with the XPO-1 inhibitor selinexor, followed by allo-HSCT at a single center between September 2024 and December 2025. At a median follow-up of 7.3 months (95% CI, 4.2-10.4 months) from HSCT, median overall survival (OS) and relapse-free survival (RFS) were not reached. At last follow-up, 7/8 patients remained alive (OS 87.5%) and 6/8 were relapse-free (RFS 75%), with one relapse (12.5%). This patient successfully achieved a second complete remission following preemptive therapy with low-dose decitabine combined with donor lymphocyte infusion and remained in remission at the last follow-up. Two patients developed serious infections during the peritransplant period. One patient with pre-transplant intestinal colonization of carbapenem-resistant Enterobacteriaceae (CRE) ultimately died due to CRE bloodstream infection followed by intestinal graft-versus-host-disease (GVHD). Overall treatment-related toxicity was deemed manageable, and the incidence of grade III-IV acute GVHD was 25% (2/8). This preliminary study provides encouraging evidence that sequential decitabine and selinexor therapy followed by allo-HSCT may improve outcomes with acceptable toxicity in patients with ultra-high-risk MDS-biTP53. However, these findings are limited by the small sample size, relatively short follow-up, and retrospective, single-center design. Confirmation in larger prospective trials is warranted.
    Keywords:  Allogeneic hematopoietic stem cell transplantation; MDS-biTP53 ; XPO-1 inhibitor
    DOI:  https://doi.org/10.1186/s40164-026-00817-w
  10. J Clin Med. 2026 Jul 27. pii: 5844. [Epub ahead of print]15(15):
    A53-Adapted Decitabine-Containing R-CHOP in Newly Diagnosed Diffuse Large B-Cell Lymphoma Defined by LymphGen: Preliminary Results of a Prospective Proof-of-Concept Study.
    Marat Mingalimov, Elena Baryakh, Polina Chernova, Andrey Misyurin, Elena Misyurina, Mariia Orlova, Tatiana Tolstykh, Ekaterina Zotina, Liliia Shimanovskaia, Tatiana Chudnova, Olga Kochneva, Kseniya Tsurkina, Dmitry Lebedev, Georgii Tyshkevich, Viktoriia Basova, Mira Suvorina, Mikhail Donskoy, Ivan Abramov, Natalia Bodunova, Saida Gadzhieva, Tatiana Semina, Sergey Andreev, Mariana Lysenko.
      Background: Diffuse large B-cell lymphoma (DLBCL) with TP53 abnormalities, corresponding to the LymphGen A53 molecular subtype, represents a biologically high-risk group associated with primary resistance to standard R-CHOP therapy. Epigenetic sensitization using hypomethylating agents may enhance chemosensitivity in this setting. We prospectively evaluated the clinical activity and safety of a molecularly adapted DAC-R-CHOP regimen in newly diagnosed A53-DLBCL. Methods: In this single-center prospective pilot cohort study, 70 consecutive patients with newly diagnosed DLBCL underwent targeted next-generation sequencing using a 60-gene panel with integrated copy number variation analysis. Six patients (8.5%) were classified as the A53 subtype. All patients received one cycle of standard R-CHOP. From cycle 2 onward, A53 patients received decitabine (10 mg/m2 IV, days 1-5) prior to R-CHOP (DAC-R-CHOP), for a total of six cycles. The primary endpoint was complete metabolic response (CMR) according to Lugano 2014 criteria. Exact 95% confidence intervals (CI) were calculated. Results: The median age of the A53 cohort was 65 years. CMR was achieved in all six patients (100%; 95% CI, 54-100%). At a median follow-up of 6 months, all patients remained alive in confirmed CMR. Grade III-IV hematologic toxicity occurred in all cases. Febrile neutropenia developed in 100% of patients, requiring mandatory G-CSF support and anti-infective therapy; no treatment-related mortality or permanent dose reductions were observed. Two patients (33%) experienced gastrointestinal bleeding related to local tumor lysis, which was managed conservatively without protocol discontinuation. Conclusions: In this prospective molecularly stratified pilot cohort, integration of decitabine into front-line immunochemotherapy showed promising clinical activity in A53-DLBCL, albeit at the cost of substantial hematologic toxicity requiring intensive supportive care. Given the small sample size, short follow-up, and absence of a comparator arm, these findings should be considered hypothesis-generating and warrant validation in larger multicenter phase II studies with integrated translational biomarker analyses.
    Keywords:  A53 subtype; LymphGen; TP53; decitabine; diffuse large B-cell lymphoma; epigenetic therapy
    DOI:  https://doi.org/10.3390/jcm15155844
  11. Cancer Sci. 2026 Aug 12.
    Quizartinib Resistance Mutations and Treatment Outcomes in Relapsed or Refractory FLT3-ITD-Positive AML.
    Yuichiro Semba, Toshihiro Miyamoto, Senji Kasahara, Yoshikane Kikushige, Takahiro Maeda, Goichi Yoshimoto, Shuichi Ota, Akio Saito, Yuho Najima, Hiroki Hosoi, Daigo Niiya, Koji Kato, Koji Nagafuji, Takashi Akasaka, Tomohiko Kamimura, Atsushi Takita, Maiko Narahara, Tadashi Toki, Koichi Iwanaga, Koji Yonemoto, Mine Harada, Koichi Akashi.
      Quizartinib is a FMS-like tyrosine kinase 3 (FLT3) inhibitor indicated for FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukemia (AML). We aimed to evaluate quizartinib resistance mechanisms, in addition to efficacy and safety outcomes, in patients with relapsed or refractory FLT3-ITD-positive AML. This multicenter, single-arm study in Japan (jRCTs071200015) enrolled 18 patients between May 2020 and December 2022. Of these, 15 patients received oral quizartinib (up to 53 mg once daily) for up to 12 cycles of 28 days each, then were followed for 12 months. The primary endpoint was to evaluate the type and rate of quizartinib resistance mutations; secondary endpoints included composite complete remission (CRc) rate, overall response rate (ORR), hematopoietic stem cell transplantation (HSCT) rate, relapse-free survival (RFS), overall survival (OS), and adverse events (AEs). Among seven evaluable patients, acquired mutations were detected in four patients (NF1 [R2616X], CSF3R [Q754X], NRAS [G13R], and FLT3 [D835Y] in one patient each), while loss of FLT3-ITD was observed in two patients. In efficacy analyses (n = 15), CRc rate was 66.7% (95% confidence interval [CI], 38.4-88.2), ORR was 73.3% (44.9-92.2), and median OS was 13.6 months (5.4-not evaluable). Three patients (20.0%) received HSCT directly after quizartinib; in these patients, median RFS was 8.5 months (95% CI, 6.2-not evaluable). Grade ≥ 3 non-hematologic AEs and grade 1 QT prolongation were each reported in three patients (20.0%). These data offer additional information on potential resistance mechanisms in patients with relapsed or refractory FLT3-ITD-positive AML. Trial Registration: Japan Registry of Clinical Trials (jRCTs071200015).
    Keywords:  FMS‐like tyrosine kinase 3; acute myeloid leukemia; drug resistance; next‐generation sequencing; quizartinib
    DOI:  https://doi.org/10.1111/cas.70485
  12. Blood Adv. 2026 Aug 25. 10(16): 5692-5693
    FLT3-ITD MRD is here to stay.
    Mark J Levis.
      
    DOI:  https://doi.org/10.1182/bloodadvances.2026021249
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