bims-hemali 2026-07-19 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2026–07–19
twenty papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Asciminib as first-line therapy in chronic myeloid leukemia: a systematic review.
Asciminib monotherapy in patients with BCR::ABL1 T315I-mutated chronic-phase chronic myeloid leukemia: phase 1 trial final results.
Efficacy and safety analysis of a novel BTK inhibitor in patients with mantle cell lymphoma harboring TP53 mutations.
Therapeutic drug monitoring guides personalized ponatinib dose reduction for chronic myeloid leukemia.
Blinatumomab consolidation for high-risk Ph- B-ALL.
Selinexor plus tislelizumab in patients with relapsed/refractory NK/T-cell lymphoma after failure of PD-1 blockade: the phase 1b TOUCH trial.
Feasibility and Safety of Venetoclax for Cytoreduction During Induction Therapy in Newly Diagnosed Acute Promyelocytic Leukemia.
The fellowship of the ring: TMEM187 guides iron to heme.
Prevalence and Prognostic Impact of ASXL1 Somatic Mutation in Patients with Chronic Myeloid Leukemia: A Systematic Review and Meta-Analysis.
Discovery of BBI-355, a Potent, Selective, and Orally Available Checkpoint Kinase 1 Inhibitor for the Treatment of Extrachromosomal DNA Oncogene-Amplified Cancers.
End-of-treatment positron emission tomography/computed tomography complete remission is highly prognostic in nodal peripheral T-cell lymphoma: An Australasian-Canadian collaborative study.
Myelofibrosis treatment sequencing: mutation-informed risk and optimal JAK inhibitor discontinuation.
Case Report: Long-term survival of refractory high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements through glofitamab monotherapy consolidated by ASCT.
Prognostic impact of measurable residual disease in AML patients treated frontline with azacitidine and venetoclax: results from the French VENAURA registry.
The efficacy, safety, and rationale of orelabrutinib combined with obinutuzumab (O2) as a first-line systemic treatment for marginal zone lymphoma.
Time to Stop? Rethinking the Duration of Maintenance Treatment in Multiple Myeloma.
Englumafusp alfa plus glofitamab in B cell non-Hodgkin lymphoma: a phase 1 trial.
Ten-day decitabine vs "3+7" in patients with AML aged ≥60 years: long-term results of the randomized phase 3 EORTC trial AML21.
Longitudinal analysis of tyrosine kinase inhibitor therapy outcomes and BCR-ABL1 transcript decline velocity in chronic myeloid leukemia: A 16-year real-world study.
The novel agent VP79s synergistically enhances venetoclax activity in multiple myeloma cells.

Blood Res. 2026 Jul 15. pii: 36. [Epub ahead of print]61(1):

Asciminib as first-line therapy in chronic myeloid leukemia: a systematic review.

Korean Society of Hematology Chronic Myeloid Leukemia Working Party

   PURPOSE: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the BCR::ABL1 fusion oncogene. Asciminib, a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor, represents a novel therapeutic approach distinct from conventional ATP-competitive tyrosine kinase inhibitors (TKIs). This systematic review evaluated the efficacy and safety of asciminib as first-line therapy in patients with newly diagnosed chronic-phase CML.
METHODS: We conducted a comprehensive systematic review following PRISMA guidelines. Electronic searches were performed in PubMed, Embase, the Cochrane Library, and clinical trial registries through December 2025. Eligible studies included randomized controlled trials, prospective cohort studies, and compassionate use programs evaluating asciminib as first-line therapy in adult patients with chronic-phase CML. Primary outcomes included molecular response rates (major molecular response [MMR], MR4, and MR4.5), whereas secondary outcomes included safety profiles and treatment discontinuation rates.
RESULTS: The systematic review identified eight eligible studies comprising more than 500 patients. In the pivotal ASC4FIRST phase 3 trial (n = 405), asciminib demonstrated superior efficacy compared with investigator-selected TKIs. At 96 weeks, MMR rates were 74.1% with asciminib compared with 52.0% with investigator-selected TKIs (treatment difference, 22.4%; 95% CI, 13.6-31.3%; P < .001) and 76.2% with asciminib compared with 47.1% with imatinib (treatment difference, 29.7%; 95% CI, 17.6-41.8%; P < .001). The ASCEND study (n = 101) reported an MMR rate of 79% at 12 months. The safety profile was distinct from that of ATP-competitive TKIs. Hypertension occurred more frequently with asciminib (all grades, 10.5%; grade ≥ 3, 5.5%), whereas arterial occlusive events (all grades: asciminib, 2.0%; investigator-selected TKIs, 1.5%) and clinical pancreatitis (all grades, 1.0% in both groups) occurred at comparable rates between the treatment groups. Treatment discontinuation due to adverse events was lower with asciminib (5.0%) than with second-generation TKIs (12.7%).
CONCLUSION: Asciminib demonstrates superior efficacy and a favorable benefit-risk profile as first-line therapy for CML, with higher molecular response rates than both imatinib and second-generation TKIs. Asciminib also has a favorable tolerability and safety profile; however, close monitoring for cardiovascular and pancreatic toxicities is required. These findings support asciminib as an effective treatment option for newly diagnosed chronic-phase CML.

Keywords:  Asciminib; BCR::ABL1; Chronic myeloid leukemia; First-line therapy; Molecular response; Tyrosine kinase inhibitor

DOI:  https://doi.org/10.1007/s44313-026-00153-2
Leukemia. 2026 Jul 16.

Asciminib monotherapy in patients with BCR::ABL1 T315I-mutated chronic-phase chronic myeloid leukemia: phase 1 trial final results.

Jorge E Cortes, Delphine Rea, Michael J Mauro, Andreas Hochhaus, Dong-Wook Kim, Koji Sasaki, Fabian Lang, Michael C Heinrich, Massimo Breccia, Michael Deininger, Yeow-Tee Goh, Jeroen J W M Janssen, Moshe Talpaz, Valle Gómez García de Soria, Philipp le Coutre, Francois-Xavier Mahon, Daniel J DeAngelo, Andrea Damon, Shruti Kapoor, Gessami Sanchez-Olle, Matthias Hoch, Nithya Agrawal, Sara Quenet, Timothy P Hughes.

In chronic myeloid leukemia in chronic phase (CML-CP), BCR::ABL1T315I commonly leads to treatment resistance, worse patient outcomes, and limited subsequent treatment options. By targeting the ABL1 myristoyl pocket, asciminib maintains activity against BCR::ABL1T315I. We report final long-term safety, tolerability, and efficacy results with asciminib in 48 patients with T315I-mutated CML-CP who received asciminib 200 mg twice daily in the phase 1, nonrandomized trial (NCT02081378). After a median exposure of 3.5 years, 52.1% of patients continued to receive asciminib via posttrial access. Of 45 evaluable patients, 24 (53.3%) achieved major molecular response (MMR); 20 of 24 maintained or deepened their response by the cutoff. The Kaplan-Meier estimated proportion of patients maintaining their first MMR for at least 144 weeks (2.8 years) was 86% (95% CI: 71.9-100.0%). The safety profile showed no new or worsening safety signals. With 1.4 years' additional exposure since the previous analysis, the incidence of grade ≥3 adverse events (AEs) (60.4%) did not increase. Four patients (8.3%) discontinued due to AEs. The exposure-adjusted incidence rate of first all-grade AOEs was 4.4 cases per 100 patient-years. With up to approximately 6 years of exposure, this final analysis confirms asciminib as a treatment option for patients with T315I-mutated CML-CP.

DOI: https://doi.org/10.1038/s41375-026-02972-9
Am J Cancer Res. 2026 ;16(6): 2481-2492

Efficacy and safety analysis of a novel BTK inhibitor in patients with mantle cell lymphoma harboring TP53 mutations.

Min Liu, Yannong Ding, Hui Lan.

   OBJECTIVE: To rigorously evaluate the efficacy and safety of a novel Bruton tyrosine kinase inhibitor (BTKi), alone or in combination with venetoclax, in patients with TP53-mutated mantle cell lymphoma (MCL), focusing on survival outcomes, depth of response, minimal residual disease (MRD), clearance, and treatment-emergent toxicities.
METHODS: We conducted a retrospective, observational cohort study of consecutive adults with TP53-mutated MCL treated with BTKi-based regimens between January 2022 and December 2025. Patients were assigned to BTKi monotherapy (ibrutinib or acalabrutinib; n = 108) or BTKi plus venetoclax (n = 112). Clinical, pathological, and genomic data were recorded using standardized electronic case-report forms. Responses were assessed according to contemporary MCL criteria, and recurrence/progression-free survival (RFS/PFS) and overall survival (OS) were calculated from predefined time points.
RESULTS: Combined treatment significantly prolonged median RFS from 11 to 34 months (HR for recurrence or death 0.42, 95% CI 0.29-0.61; P<0.001), and median OS from 20 to 50 months (HR 0.44, 95% CI 0.31-0.63; P<0.001). Overall response rates were higher with BTKi-based combination therapy (76.8% vs. 58.3%; P = 0.001), with comparable rates of complete response. In multivariable models, BTKi-based combination therapy remained independently associated with longer PFS (HR 0.187, 95% CI 0.079-0.442; P<0.001).
CONCLUSION: In patients with TP53-mutated MCL, BTKi-based combination therapy confers clinically meaningful and durable improvements in RFS and OS, with higher overall response rates than monotherapy and acceptable toxicity profiles.

Keywords:  BTK inhibitor; TP53 mutations; efficacy; mantle cell lymphoma; safety

DOI:  https://doi.org/10.62347/RDKL6452
Int J Hematol. 2026 Jul 14.

Therapeutic drug monitoring guides personalized ponatinib dose reduction for chronic myeloid leukemia.

Maiko Abumiya, Naoto Takahashi.

  The arterial occlusive events (AOEs) associated with ponatinib are dose-dependent. Although the phase II OPTIC trial showed that reducing the dose to 15 mg daily (QD) after achieving a response provided an optimal benefit-risk profile, this has not been adequately verified using plasma drug concentrations data. A 66-year-old woman with chronic-phase chronic myeloid leukemia (CP-CML) was switched to ponatinib because of nilotinib-induced grade 3 thrombocytopenia. For safety, ponatinib was initiated at 15 mg every other day (Q2D) and gradually increased to 45 mg QD. A major molecular response (MMR) was achieved 30.6 months after starting ponatinib. The dose was then reduced to 15 mg QD to mitigate cardiovascular risks, and the MMR was successfully sustained for approximately 2 years (21.2 months) at this reduced dose. The total overall observation period was more than 5 years (65.2 months). A strong correlation was observed between the ponatinib dose and plasma trough concentrations (R2 = 0.8132). Although 30 mg QD was required to reach the target concentration for suppressing resistant clones (23 ng/mL), MMR was sustained at 15 mg QD, with a trough level of 14.1 ng/mL. Once the tumor burden is significantly reduced, lower concentrations of ponatinib may be sufficient to maintain the molecular response.

Keywords:  Arterial occlusive events; Chronic myeloid leukemia; OPTIC trial; Ponatinib; Therapeutic drug monitoring

DOI:  https://doi.org/10.1007/s12185-026-04254-7
Blood. 2026 Jul 16. 148(3): 390

Blinatumomab consolidation for high-risk Ph- B-ALL.

DOI: https://doi.org/10.1182/blood.2026035018
Oncologist. 2026 Jul 11. pii: oyag266. [Epub ahead of print]

Selinexor plus tislelizumab in patients with relapsed/refractory NK/T-cell lymphoma after failure of PD-1 blockade: the phase 1b TOUCH trial.

Chuanxu Liu, Dahui Li, Yan Gao, Wenhao Zhang, Zhi Guo, Jun Zhao, Huiqiang Huang, Rong Tao.

   BACKGROUND: Relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R NKTCL) remains a highly lethal disease, particularly after failure of PD-1 blockade-based therapy. Preclinical data suggest that inhibition of exportin-1 (XPO1) may enhance antitumor immunity and synergize with PD-1 blockade.
PATIENTS AND METHODS: We conducted a multicenter, open-label phase 1 b study (TOUCH, Arm C) evaluating selinexor plus tislelizumab in patients with R/R NKTCL previously treated with L-asparaginase-containing regimens. A standard 3 + 3 dose-escalation design was followed by dose expansion.
RESULTS: Seventeen patients were enrolled; 16 had prior checkpoint inhibitor (CPI) exposure and comprised the efficacy population. No dose-limiting toxicities were observed. Grade ≥3 treatment-emergent adverse events occurred in 52.9% of patients; hematologic toxicities were the most common. Among patients with prior CPI exposure, the overall response rate was 75.0% (12/16), including complete responses in 43.8% (7/16). Responses were observed in patients with primary CPI-refractory disease. With a median follow-up of 21.7 months, median progression-free survival was 6.1 months (95% CI, 2.9-not estimable), and the 2-year progression-free survival rate was 37.5%. Median overall survival was not reached; the 2-year overall survival rate was 73.4%.
CONCLUSION: Selinexor plus tislelizumab demonstrated manageable toxicity and substantial activity in patients with relapsed/refractory NKTCL previously treated with CPI, supporting further evaluation of nuclear export inhibition as a strategy to re-engage antitumor immunity after failure of PD-1 blockade.
CLINICALTRIALS.GOV IDENTIFIER: NCT04425070.

Keywords:  Extranodal NK/T-cell lymphoma; PD-1 blockade resistance; XPO1 inhibition; selinexor; tislelizumab

DOI:  https://doi.org/10.1093/oncolo/oyag266
Eur J Haematol. 2026 Jul 13.

Feasibility and Safety of Venetoclax for Cytoreduction During Induction Therapy in Newly Diagnosed Acute Promyelocytic Leukemia.

Yu Wang, Rong Xiao, Xiaobing Huang, Yi Xiao.

   OBJECTIVE: This study aimed to evaluate the feasibility and safety of venetoclax as a cytoreductive strategy during induction therapy in newly diagnosed acute promyelocytic leukemia (APL), and to provide an exploratory description of its early efficacy.
METHODS: This was a single-center retrospective analysis including 29 patients newly diagnosed with APL between January 2023 and December 2025. All patients received induction therapy with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) and were treated with different cytoreduction strategies based on clinical decision-making: venetoclax group (n = 16) or conventional cytoreduction group (hydroxyurea ± anthracycline, n = 13).
RESULTS: The proportion of hematologic complete recovery (HCR) at Day 28 was significantly higher in the venetoclax group than in the conventional group (93.75% vs. 46.15%, p = 0.003). The median time to HCR was shorter in the venetoclax group (26 vs. 28 days, p = 0.002). The median time to molecular complete remission (MCR) was also shorter (92 vs. 110 days, p = 0.001). In addition, the venetoclax group required significantly fewer red blood cell and platelet transfusions and had a shorter duration of hospitalization. There was no statistically significant difference in the incidence of differentiation syndrome (DS) between the two groups.
CONCLUSION: Venetoclax appears to be a feasible and safe cytoreductive option during induction therapy in APL and may be associated with faster hematologic recovery. These findings require further validation in prospective studies.

Keywords:  acute promyelocytic leukemia; bleeding; induction therapy; venetoclax

DOI:  https://doi.org/10.1111/ejh.70264
Blood. 2026 Jul 16. 148(3): 271-272

The fellowship of the ring: TMEM187 guides iron to heme.

Yvette Y Yien.

DOI: https://doi.org/10.1182/blood.2026033658
Cancers (Basel). 2026 Jun 24. pii: 2041. [Epub ahead of print]18(13):

Prevalence and Prognostic Impact of ASXL1 Somatic Mutation in Patients with Chronic Myeloid Leukemia: A Systematic Review and Meta-Analysis.

Rita Ahmad, Motaz Almahmood, Rasha Kaddoura, Muhammad Ali Tariq, Ayman Abdullah Dalol, Marrita Rabadi, Aadhila Abbas Manthiri, Abdulrahman F Al-Mashdali, Hatem Ahmed, Mohammed Abdulgayoom, Ayah Al Qaryoute, Sara Westall, Fadi Haddad, Shehab F Mohamed.

  Background: Outcomes in chronic myeloid leukemia (CML) remain heterogeneous despite effective BCR::ABL1 tyrosine kinase inhibitors (TKIs). Somatic mutations in epigenetic regulators, particularly additional sex combs-like 1 (ASXL1), have been implicated in adverse prognosis, but their clinical impact in CML has not been systematically defined. Methods: A systematic review was conducted using CINAHL, EMBASE, MEDLINE Ultimate, and PubMed from inception through August 2025. A total of 1339 records were identified; the eligible studies included adult and pediatric patients with chronic and advanced-phase (accelerated or blast) CML. After duplicate removal and screening, 11 studies met the inclusion criteria; these included adult patients only and were included in a qualitative synthesis and meta-analysis. ASXL1 mutation status was assessed using validated molecular methods. The outcomes included the molecular response, cytogenetic response, survival, and treatment resistance. Random-effects models were used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I2 statistic. Results: Across the included studies, ASXL1 mutations were detected in approximately 15% of patients. At 12 months, patients with ASXL1 mutations had significantly lower odds of achieving a major molecular response (MMR) compared with ASXL1-wildtype patients (OR 0.29; 95% CI 0.16-0.51; p < 0.0001; I2 = 30%). No statistically significant difference was observed in the complete cytogenetic response (CCyR) (OR 0.30; 95% CI 0.02-5.31; p = 0.41; I2 = 68%). Compared with patients harboring other non-ASXL1 somatic mutations, an ASXL1 mutation was not associated with a significant difference in MMR (OR 0.49; 95% CI 0.23-1.05; p = 0.067; I2 = 0%). Conclusions: ASXL1 mutations may be associated with an inferior molecular response to TKI therapy in CML, supporting their role as an adverse prognostic biomarker. These findings highlight the potential value of incorporating myeloid mutation profiling into future CML risk-stratification strategies.

Keywords:  ASXL1 mutation; CML; TKIs; chronic myeloid leukemia

DOI:  https://doi.org/10.3390/cancers18132041
J Med Chem. 2026 Jul 15.

Discovery of BBI-355, a Potent, Selective, and Orally Available Checkpoint Kinase 1 Inhibitor for the Treatment of Extrachromosomal DNA Oncogene-Amplified Cancers.

S Todd Meyer, Sudhir Chowdhry, Rachelle J Elsdon, Jacques Mauger, Yen P H Truong, Ryan Hansen, Joshua Plum, Auzon Steffy, AnneMarie Pferdekamper, Benjamin Norman, Salvador Garcia, Edison Tse, Julius Apuy, Ardalan Ardeshiri, Shailaja Kasibhatla, Christian A Hassig, Anthony B Pinkerton.

Checkpoint kinase 1 (CHK1), a master regulator of replication stress, has been investigated as a potential therapeutic target for over two decades. More recently, CHK1 has been implicated as a target for the treatment of ecDNA-driven, oncogene-amplified cancers. However, clinical-stage CHK1 inhibitors have historically faced challenges related to dosing schedule, tolerability, and clinical efficacy, although recent studies suggest that biomarker-driven approaches and alternative dosing strategies may address some of these limitations. Structure-guided optimization led to the discovery of BBI-355, a potent, selective, and orally available CHK1 inhibitor. BBI-355 demonstrates strong antitumor activity when dosed orally in mouse xenograft models, achieving regressions both as a single agent and in combination with targeted therapies. BBI-355 also displays favorable ADMET and PK properties and has been advanced to a clinical trial for patients with oncogene amplified cancers.

DOI: https://doi.org/10.1021/acs.jmedchem.6c00822
Br J Haematol. 2026 Jul 17.

End-of-treatment positron emission tomography/computed tomography complete remission is highly prognostic in nodal peripheral T-cell lymphoma: An Australasian-Canadian collaborative study.

Chathuri Abeyakoon, Cameron Wellard, Vanessa Murad, Eliza Chung, David Hodgson, Danielle Rodin, Anca Prica, Tomohiro Aoki, Abi Vijenthira, Umberto Falcone, Stephen Opat, Erica M Wood, Zoe K McQuilten, Eliza A Hawkes, Michael Crump, John Kuruvilla, Gareth P Gregory.

  While end-of-treatment (EOT) imaging after front-line therapy is prognostic in nodal peripheral T-cell lymphoma (PTCL), its subtype-specific significance remains unclear. Retrospective review of patients with nodal PTCL included in the Australasian Lymphoma and Related Diseases Registry and the Princess Margaret Cancer Centre lymphoma database between 2011 and 2024. Progression-free survival (PFS), overall survival (OS), and positive and negative predictive values (PPV/NPV) of an EOT positron emission tomography/computed tomography response were evaluated. We identified 451 patients. Median follow-up was 43.1-months (95% confidence interval [CI] 38.8%-48.3%). Patients achieving an EOT imaging complete remission (CR) had a 36-month PFS of 43.1% (95% CI 34.3%-51.5%). The 36-month OS was significantly higher in patients achieving CR compared with those who did not achieve a CR (73.5% [95% CI 65.3%-80%] vs. 20.9% [95% CI 12.9%-30.2%]; p < 0.001). EOT imaging CR remained prognostic for OS in all nodal PTCL subtypes (p < 0.001). At 36-months, EOT PET demonstrated a PPV of 90% (95% CI 80.5%-96.2%) and a NPV of 43.1% (95% CI 34.3%-51.5%). EOT PET/CT CR is strongly prognostic of OS across nodal PTCL subtypes with a high PPV for predicting death but poor NPV for predicting survival. Outcomes remain poor for patients not achieving a CR, with suboptimal outcomes even in those achieving CR.

Keywords:  CT response; PET response; nodal T‐cell lymphoma; peripheral T‐cell lymphoma; survival outcomes

DOI:  https://doi.org/10.1111/bjh.70689
Expert Rev Hematol. 2026 Jul 13. 1-13

Myelofibrosis treatment sequencing: mutation-informed risk and optimal JAK inhibitor discontinuation.

Giulia Benevolo, Giuseppe Lanzarone, Benedetta Rosti, Eloise Beggiato.

   INTRODUCTION: Myelofibrosis (MF) is a heterogeneous myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, cytopenias, and risk of leukemic transformation. As therapeutic options expand, treatment discontinuation and sequencing are increasingly recognized as clinically relevant determinants of patient outcomes.
AREAS COVERED: A literature search was performed using PubMed/MEDLINE and major hematology conference proceedings (ASH and EHA), covering publications from January 2010 through February 2026. This review discusses mutation-informed risk stratification, current and emerging JAK inhibitor treatment sequencing strategies, and practical approaches to treatment discontinuation and therapeutic transition in MF.
EXPERT OPINION: Optimizing outcomes in MF increasingly requires proactive transition management rather than reactive treatment interruption. Early identification of treatment failure, phenotype-guided therapeutic sequencing, and integration of molecular risk assessment may improve long-term disease management and could contribute to better clinical outcomes, although prospective confirmation remains necessary.

Keywords:  JAK inhibitor discontinuation; Myelofibrosis; allogeneic stem cell transplantation; high molecular risk mutations; mutation profiling; myelofibrosis survival; ruxolitinib; treatment sequencing

DOI:  https://doi.org/10.1080/17474086.2026.2688872
Front Immunol. 2026 ;17 1857464

Case Report: Long-term survival of refractory high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements through glofitamab monotherapy consolidated by ASCT.

Fang Fang, Jing Ni, Hong Zhao, Wuhan Hui, Xuejing Sun, Dongmei Zou, Wanling Sun.

  Patients with high-grade B-cell lymphoma (HGBCL), who are in early relapse or primary refractory, always have poor outcomes. Even intensive chemotherapy or CAR-T cell therapy is not always the best solution. Here is a case of refractory high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements (triple-hit HGBCL), who achieved complete metabolic remission (CMR) following six cycles of glofitamab monotherapy induction and followed by autologous stem cell transplantation (ASCT) consolidation. The patient has achieved a sustained CMR and a progression-free survival (PFS) of 25 months (ongoing) from progression. Hepatitis B virus (HBV) seroconversion occurred during ASCT before stem cell engraftment, and was effectively suppressed with entecavir. Immune function was monitored in our case by flow cytometry. Downregulation of PD-1 expression on T cells and a reduced proportion of regulatory T cells (Tregs) were observed, consistent with fully activated immune function, which may explain why the patient responded rapidly and maintained durable efficacy. Immune analysis also exhibited B cell subset exhaustion and a disrupted naïve/memory T cell ratio which suggested an immunosenescence phenotype. It is speculated that an over activation of immune function promotes immunosenescence following bispecific antibody therapy, this needs attention. This case highlights the potential of glofitamab induction followed by ASCT consolidation to achieve durable remission in aggressive triple-hit HGBCL. The immune function after bispecific antibody treatment should be monitored and needs further investigation.

Keywords:  autologous stem cell transplantation (ASCT); bispecific antibody; early progression; high-grade B-cell lymphoma; immune

DOI:  https://doi.org/10.3389/fimmu.2026.1857464
Leukemia. 2026 Jul 17.

Prognostic impact of measurable residual disease in AML patients treated frontline with azacitidine and venetoclax: results from the French VENAURA registry.

French AURAML group

Measurable residual disease (MRD) is a key prognostic marker in acute myeloid leukemia (AML), but its significance in patients treated with azacitidine and venetoclax (AZA/VEN) outside clinical trials remains unclear. We retrospectively analyzed 220 newly diagnosed AML patients from the French VENAURA registry who achieved composite complete remission and underwent MRD evaluation by multiparametric flow cytometry (MFC, LAIP/LSC) and/or NPM1 RT-qPCR. Cumulative MRD negativity was achieved in 62-67% of patients. Attaining MRD negativity at any time was strongly associated with superior overall survival (OS: 31.3 months vs 15.7 months (HR = 0.47) for LAIP, not reached vs 10.8 months (HR = 0.38) for NPM1; all p < 0.001) and lower cumulative incidence of relapse. Dual LAIP/LSC negativity (NEG/NEG) conferred the best outcomes compared to NEG/POS (HR = 0.36, p = 0.02), POS/NEG (HR = 0.24, p < 0.001) and POS/POS (HR = 0.26, p = 0.26) status. Importantly, MRD response mitigated the adverse prognostic impact of ELN 2024 intermediate/poor risk, with MRD-negative patients achieving outcomes comparable to favorable-risk cases. MRD kinetics (early vs late responders) did not affect survival, while G-CSF use improved MRD conversion and OS. In real-world AZA/VEN-treated AML, achieving deep MRD negativity, by MFC or NPM1 RT-qPCR, emerges as the dominant prognostic determinant, overriding baseline risk and supporting its integration into response-adapted strategies.

DOI: https://doi.org/10.1038/s41375-026-03024-y
Blood Cancer J. 2026 Jul 11. pii: 114. [Epub ahead of print]16(1):

The efficacy, safety, and rationale of orelabrutinib combined with obinutuzumab (O2) as a first-line systemic treatment for marginal zone lymphoma.

Jiadai Xu, Jing Li, Yuhong Ren, Luya Cheng, Zhixiang Cheng, Jingli Zhuang, Yang Ke, Shiyang Gu, Yian Zhang, Feifei Chen, Rupan Gao, Panpan Li, Yaqin Xiong, Peng Liu.

DOI: https://doi.org/10.1038/s41408-026-01575-y
N Engl J Med. 2026 Jul 16. 395(3): 302-303

Time to Stop? Rethinking the Duration of Maintenance Treatment in Multiple Myeloma.

Hira Mian, Luciano J Costa.

DOI: https://doi.org/10.1056/NEJMe2604761
Nat Med. 2026 Jul 16.

Englumafusp alfa plus glofitamab in B cell non-Hodgkin lymphoma: a phase 1 trial.

Martin Hutchings, Michael Dickinson, Giuseppe Gritti, Carmelo Carlo-Stella, William Townsend, Francesc Bosch, Nancy L Bartlett, Guillaume Cartron, Herve Ghesquieres, Roch Houot, Harriet Walter, Fritz Offner, Natalie Dimier, Candice Jamois, Sylvia Herter, Abiraj Keelara, Sabine Wilson, Jeremy Gallien, Heather Hinton, Isabel Prieto Gonzalez-Albo, Koorosh Korfi, Georgios Kazantzidis, Marie-Hélène Wasmer, Katharina Lechner, Franck Morschhauser.

There is an unmet need for effective, off-the-shelf therapies for relapsed or refractory aggressive B cell non-Hodgkin lymphoma (B-NHL). Part 2 of the current study was an open-label, nonrandomized, phase 1 study of escalating doses of the CD19-4-1BBL co-stimulatory molecule, englumafusp alfa, in combination with glofitamab in patients with relapsed or refractory B-NHL. Obinutuzumab pretreatment was administered 7 days before the first glofitamab dose. Glofitamab step-up dosing in cycle 1 was followed by 11 cycles of glofitamab plus englumafusp alfa. Englumafusp alfa was administered at escalating doses, with the initial dose on cycle 2 day 8 (C2D8) or cycle 1 day 10 (C1D10). Primary objectives were to establish the maximum tolerated dose, and safety and tolerability. A total of 134 patients were enrolled, including 109 with aggressive B-NHL and 25 with indolent B-NHL. The maximum tolerated dose of englumafusp alfa was not reached; one dose-limiting toxicity occurred (grade 5 Pneumocystis jirovecii pneumonia). Adverse events were reported in 98.5% of all patients, with grade 3/4 adverse events in 59.0%. Grade 5 adverse events occurred in ten patients. In the subgroup of C2D8 patients with aggressive B-NHL (n = 83), overall response and complete metabolic response rates were 68.7% and 56.6%, respectively; among those without previous exposure to chimeric antigen receptor T cell therapy (n = 41), the corresponding rates were 73.2% and 65.9%. Pharmacodynamic changes following englumafusp alfa administration supported its co-stimulatory mode of action. These data demonstrate that the addition of englumafusp alfa to glofitamab is associated with encouraging efficacy and robust pharmacodynamic modulation, as well as a safety profile consistent with glofitamab monotherapy, in patients with relapsed or refractory B-NHL. CTIS identifier: 2022-502616-37-00 ; ClinicalTrials.gov identifier: NCT04077723 .

DOI: https://doi.org/10.1038/s41591-026-04533-0
Blood Neoplasia. 2026 Aug;3(3): 100246

Ten-day decitabine vs "3+7" in patients with AML aged ≥60 years: long-term results of the randomized phase 3 EORTC trial AML21.

EORTC Leukemia Group, Italian Group for Adult Hematologic Diseases, and German MDS Study Group

DOI: https://doi.org/10.1016/j.bneo.2026.100246
Cancer. 2026 Jul 15. 132(14): e70524

Longitudinal analysis of tyrosine kinase inhibitor therapy outcomes and BCR-ABL1 transcript decline velocity in chronic myeloid leukemia: A 16-year real-world study.

Moaath K Mustafa Ali, Emily C Zabor, Kamilla Abdurakhmanov, Hadil Zureigat, Ahmed N Mohamed, Muaz Alsabbagh Alchirazi, Aastha Dhakal, Ali Mushtaq, Naveen Rehman, Ameed Bawwab, Bryan Berube, Lana Khatib, Akriti G Jain, John C Molina, Sophia Balderman, Abhay Singh, Aaron T Gerds, Ronald Sobecks, Anjali S Advani, Hetty E Carraway, Matt Kalaycio, Sudipto Mukherjee.

   BACKGROUND: No large, randomized trials have compared three or more tyrosine kinase inhibitors (TKIs) in a single chronic myeloid leukemia (CML) cohort. Most studies are two-arm comparisons versus imatinib, or rely on indirect methods.
METHODS: A retrospective cohort study was conducted of 349 patients with chronic- and accelerated-phase CML treated between 2007 and 2023 at Cleveland Clinic centers in Northeast Ohio. Overall survival (OS), event-free survival (EFS), 12-month therapeutic milestone achievement, and BCR-ABL1 transcript decline velocity across first-, second-, and third-line TKIs were compared. Baseline demographics, comorbidities, cytogenetics, and hematologic parameters were collected. Multivariable regression and time-dependent Cox models were adjusted for confounders and varying therapy initiation times.
RESULTS: First-line TKIs included imatinib (53%), dasatinib (30%), nilotinib (15%), and bosutinib (2%). Median age ranged from 52 to 60 years, most patients were White, and high-risk cytogenetics were rare. Five-year OS ranged from 78% for dasatinib to 90% for nilotinib, with nilotinib associated with improved OS (hazard ratio [HR], 0.43) and EFS (HR, 0.48) and the fastest BCR-ABL1 decline (β = -8.3%) versus imatinib. In second- (n = 181) and third-line therapy (n = 91), no significant differences in outcomes were observed. Across all lines, time-dependent modeling showed improved EFS only for nilotinib (HR, 0.61). Unadjusted OS was higher in patients starting treatment in 2007-2010 versus later periods but differences disappeared after adjustment.
CONCLUSIONS: Real-world data indicate that imatinib achieves comparable response rates to newer TKIs, with durable survival. Nilotinib consistently shows faster BCR-ABL1 decline and improved EFS overall, consistent with prior network meta-analyses. Lack of improvement in OS over time suggests the need to investigate factors influencing long-term outcomes in CML.

Keywords:  BCR‐ABL1 kinetics; chronic myeloid leukemia; event‐free survival; overall survival; tyrosine kinase inhibitors

DOI:  https://doi.org/10.1002/cncr.70524
Invest New Drugs. 2026 Jul 17.

The novel agent VP79s synergistically enhances venetoclax activity in multiple myeloma cells.

Yunlong Pei, Jiaxun Wang, Taylor Smith, Martin Sutton, Julie David, Tianyi Gao, Patrick J Hayden, Paul V Browne, Viola Previtali, Marco Minneci, Isabel Rozas, Anthony M McElligott, Daniela M Zisterer.

  Despite advances in new therapies, multiple myeloma (MM) remains incurable with most patients relapsing or becoming refractory to treatment demonstrating the need for novel therapeutic strategies. We previously identified VP79s, a novel guanidinium-based compound, with potent anti-myeloma activity which targets the dysregulated IL-6/JAK/STAT signalling pathway. Here, we aim to further evaluate the translational potential of VP79s by examining whether it synergises with the BH3 mimetic venetoclax and exploring the mechanisms underlying this effect. The pro-apoptotic effect of VP79s and venetoclax alone or in combination was assessed by annexin V/propidium iodide staining followed by flow cytometry analysis. Western blotting was performed to evaluate the expression level of key pro- and anti-apoptotic members of the Bcl-2 family. BH3 profiling assessed apoptotic priming of cells to a Bim-domain peptide. Co-treatment of NCI-H929 and MM1.S cells with VP79s/venetoclax resulted in a synergistic enhancement of apoptosis which correlated with a decrease in anti-apoptotic Mcl-1 and concurrent increase in pro-apoptotic Bim S. Synergy was not observed in U266B1 cells possibly because these cells demonstrated relative resistance to venetoclax and exhibited a lower level of apoptotic priming in response to a Bim peptide. Importantly, co-treatment of NCI-H929 cells with VP79s and venetoclax was shown to overcome bone marrow stromal cell induced drug resistance. Preliminary findings also indicate that the combination treatment induced an enhanced reduction in viability of ex vivo myeloma patient samples with minimal cytotoxicity toward healthy donor lymphocytes observed. These findings support further preclinical investigation of VP79s in combination with venetoclax as a potential therapeutic strategy in MM.

Keywords:  Cell death; Mcl-1; Bim; VP79s; Venetoclax

DOI:  https://doi.org/10.1007/s10637-026-01629-9