bims-hemali 2026-04-26 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2026–04–26
eleven papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Mosunetuzumab plus polatuzumab vedotin in relapsed/refractory MCL after BTK inhibitor therapy: a phase 2 study.
ASC4OPT: asciminib treatment optimization study in patients with chronic myeloid leukemia in chronic phase previously treated with two or more tyrosine kinase inhibitors.
Dynamics of complete responses (CRs) in patients with relapsed or refractory follicular lymphoma (R/R FL) treated with odronextamab in the ELM-2 study.
Zanubrutinib-based regimen as the salvage or bridging treatment of CART therapy in relapsed or refractory, non-germinal center B-cell-like diffuse large B-cell lymphoma: a retrospective multicenter cohort study.
Tucidinostat Plus R-CHOP vs R-CHOP in MYC/BCL2 Double-Expressor Diffuse Large B-Cell Lymphoma: A Randomized Clinical Trial.
Exportin 1 Inhibitor Combined With Venetoclax Induces Apoptosis in Myelodysplastic Syndrome by Mitochondria-Induced Apoptosis Pathway.
Seven-day Venetoclax Combined With Dose-adjusted Intensive Chemotherapy as Induction Treatment in Newly Diagnosed Acute Myeloid Leukemia.
Philadelphia chromosome-negative but BCR::ABL1-positive acute lymphoblastic leukemia: a real-world multicenter cohort study.
From Time-Limited Therapy to Treatment-Free Observation: The Evolving Role of MRD in CLL Management.
Pharmacological boosting of azacitidine/venetoclax in acute myeloid leukemia.
First-line Polatuzumab vedotin plus R-CHP in primary mediastinal B-cell lymphoma: A real-world study bridging the gap of the POLARIX trial.

Blood. 2026 Apr 21. pii: blood.2025032422. [Epub ahead of print]

Mosunetuzumab plus polatuzumab vedotin in relapsed/refractory MCL after BTK inhibitor therapy: a phase 2 study.

Lihua E Budde, Manali Kamdar, Sarit E Assouline, Julio C Chavez, Nilanjan Ghosh, Thomas A Ollila, Daniel J Hodson, Dipenkumar Modi, Mariana Bastos-Oreiro, Seema G Naik, Shazia K Nakhoda, Connie Lee Batlevi, Jue Wang, Sneha Makadia, Antonia Kwan, Elicia Penuel, Jing Jing, Hao Wu, Wahib Ead, Song Pham, Iris To, Michael C Wei, Michael Wang.

Patients with relapsed/refractory mantle cell lymphoma (MCL), especially those progressing after Bruton tyrosine kinase (BTK) inhibitor and/or chimeric antigen receptor (CAR) T-cell therapy and those with high-risk features, have poor outcomes. The bispecific antibody, mosunetuzumab, combined with the antibody-drug-conjugate (ADC), polatuzumab vedotin (Mosun-Pola), targets CD20 and CD79b via independent cell-killing mechanisms. In this multicenter phase 2 study, patients with MCL who had received ≥2 prior lines of therapy, including a BTK inhibitor, were enrolled. Patients received outpatient fixed-duration mosunetuzumab subcutaneously (17 cycles), with Cycle 1 step-up dosing to mitigate cytokine release syndrome, and polatuzumab vedotin (1.8 mg/kg intravenously) for 6 cycles. The primary endpoint was centrally assessed best objective response rate. Forty-two patients with a median of 3 prior therapies were enrolled; 26% had prior CAR T-cell therapy. A number of patients had MCL with high-risk features (Ki-67 ≥50%, 67%; blastoid/pleomorphic morphology, 38%; TP53 aberration, 48%). Objective response occurred in 88.1% of evaluable patients (95% CI, 74.4-96.0) and complete response in 78.6% (95% CI, 63.2-89.7). With a median follow-up of 15.9 months, median progression-free survival was 18.6 months (95% CI, 13.9-not estimable). Consistent efficacy was observed in high-risk subgroups. Cytokine release syndrome occurred in 42.9% of patients and was limited to Grade 1-2 events. Mosun-Pola achieved high complete remission rates while maintaining a manageable safety profile in patients with relapsed/refractory MCL exhibiting high-risk features. This is the first bispecific-ADC combination therapy study in MCL. (Funded by F. Hoffmann-La Roche Ltd; ClinicalTrials.gov, NCT03671018).

DOI: https://doi.org/10.1182/blood.2025032422
Leukemia. 2026 Apr 23.

ASC4OPT: asciminib treatment optimization study in patients with chronic myeloid leukemia in chronic phase previously treated with two or more tyrosine kinase inhibitors.

Andreas Hochhaus, Philipp le Coutre, Dragana Milojkovic, Dennis Dong Hwan Kim, Soo Min Lim, Carolina Pavlovsky, Thanh Nguyen, Franck Emmanuel Nicolini, Beatriz Moiraghi, Sebastian Grosicki, Chi Dung Phu, Gabriel Etienne, Fernando Marco de Lucas, Rosa Maria Ayala Diaz, Massimo Breccia, Charles Chuah, Roberto Abi Rached, Himanshu Pokhriyal, Aswin Ic, Peter Schuld, Virginia Pilipovic, Franz Alisch, Carla Maria Boquimpani.

The ASC4OPT non-comparative phase 3b study (NCT04948333) evaluates asciminib once daily (QD) or twice daily (BID) in chronic myeloid leukemia in chronic phase (CML-CP) treated with ≥2 tyrosine kinase inhibitors (TKIs). This study enrolled 169 patients not in major molecular response (MMR), with unsatisfactory response (intolerant, warning or failure) as defined by European LeukemiaNet (ELN) 2020 criteria. Patients intolerant to their most recent TKI and in MMR at baseline (n = 30) were also enrolled. The primary endpoint was the MMR rate at Week 48 for patients not in MMR at baseline. Results showed an overall MMR rate of 39.4% at Week 48 (40 mg BID, 43.4%; 80 mg QD, 35.4%) and 43.6% at Week 96 (40 mg BID, 45.8%; 80 mg QD, 41.5%) in patients not in MMR at baseline. Among 40 patients who had their asciminib dose escalated to 200 mg QD, 17.5% were in MMR at Week 96. Most patients in MMR at baseline remained in MMR at 48 and 96 weeks (93.3% and 86.7%, respectively). Safety for both dosing regimens was consistent with that of previous studies. Findings support asciminib as a potential standard of care for patients with CML-CP who have not responded optimally to prior TKI therapy.

DOI: https://doi.org/10.1038/s41375-026-02965-8
Hemasphere. 2026 Apr;10(4): e70300

Dynamics of complete responses (CRs) in patients with relapsed or refractory follicular lymphoma (R/R FL) treated with odronextamab in the ELM-2 study.

Stefano Luminari, Ana Jiménez-Ubieto, Geoffrey Chong, David Tucker, Srikanth Ambati, Chinjune Lin, Hesham Mohamed, Jurriaan Brouwer-Visser, Chetachi Akunna Otele, Giovanni Antico, Jose C Villasboas.

Complete response (CR) is an important treatment goal in follicular lymphoma (FL). In relapsed or refractory (R/R) FL, CR rates decline, and disease progression accelerates with each treatment line, with particularly poor outcomes in patients with high-risk features. Odronextamab, a CD20 × CD3 bispecific antibody, demonstrated deep, durable responses and generally manageable safety in R/R FL in the Phase 2 ELM-2 study (NCT03888105); we present an exploratory analysis in patients who attained a CR. Patients received intravenous odronextamab with step-up dosing in Cycle 1, 80 mg weekly in Cycles 2-4, then 160 mg once every 2 weeks until disease progression or other protocol-defined reason for discontinuation. Patients with CR lasting ≥9 months switched to dosing once every 4 weeks. Overall, 73.4% (94/128) of patients attained CR, 93.6% (88/94) by first response assessment (~Week 12). Median time to CR was 2.7 months (range 2.3-7.9). Median duration of CR was 25.1 months (95% confidence interval [CI] 20.5-not evaluable [NE]) overall and 23.7 months (18.2-NE) in patients with high-risk features. Overall, 79.5% (35/44) of patients who switched to Q4W dosing maintained CR at last assessment. Patients with low/undetectable CD20 expression by immunohistochemistry (<10% CD20+ cells) or RNA sequencing (messenger RNA < 500 transcripts per million) could achieve CR. Median progression-free survival was 27.8 months (95% CI 23.0-NE) in patients with CR and not reached in those with undetectable circulating tumor DNA at Week 12. Treatment-emergent adverse events (TEAEs) led to treatment discontinuation in 16.0% of patients with CR; the most common TEAE was cytokine release syndrome (56.4%). This generally manageable safety profile and the sustainability of CRs support odronextamab as a potential long-term treatment for heavily pretreated R/R FL.

DOI: https://doi.org/10.1002/hem3.70300
Front Immunol. 2026 ;17 1806191

Zanubrutinib-based regimen as the salvage or bridging treatment of CART therapy in relapsed or refractory, non-germinal center B-cell-like diffuse large B-cell lymphoma: a retrospective multicenter cohort study.

Yan Lu, Shiguang Ye, Lili Zhou, Xianggui Yuan, Ping Li, Wenbin Qian, Aibin Liang.

   Background: Relapsed or refractory (R/R) non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) shows poor clinical outcomes. Bruton tyrosine kinase (BTK) inhibitors have established therapeutic activity by targeting B-cell receptor signaling, with promising results in treating DLBCL. The monotherapy of zanubrutinib, a selective BTK inhibitor, or second-line salvage chemotherapy has shown limited efficacy in patients with R/R DLBCL. Thus, the present study evaluated the efficacy and safety of zanubrutinib-combined therapy in heavily treated patients with non-GCB DLBCL.
Methods: This retrospective study consists of 27 heavily treated patients with non-GCB DLBCL who received zanubrutinib-combined therapy between January 2021 and February 2024 in Shanghai Tongji Hospital and Zhejiang Second Affiliated Hospital. Efficacy outcomes included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), whereas safety outcomes included incidence of adverse events.
Results: Of all the 27 enrolled patients' baseline,24 patients (88.9%) showed a high IPI score (≥3), 23 patients (85.2%) had a high proliferation score (Ki 67≥80%) and 20 patients (74.1%) were heavily treated with ≥3 lines of previous treatments. The ORR in all patients was 74.1% (95%CI, 53.7%-88.9%), the partial response (PR) was 66.7% (95%CI, 46.0%-83.5%). With a median follow-up of 36.6 months, the median PFS was 10.6 months (95%CI 7.3-14) and median OS was 19.6 months (95%CI 12.3-not reached). The grade ≥3 hematologic toxicities included neutropenia (85.1%, 23/27) and thrombocytopenia (37%, 10/27). The grade ≥3 nonhematologic AEs were hypokalemia (11.1%, 3/27) and pulmonary infection (11.1%, 3/27). No treatment-related deaths occurred. Subgroups stratified by gender, age, and presence/absence of extranodal lesions all maintained an ORR of over 70%. The efficacy of the combined therapy seemed to be not affected by most baseline characteristics and was associated with high response even in high-risk subgroups. Of all the evaluated 27 patients, 2 patients got complete response (CR) received autologous stem cell transplantation and lenalidomide maintenance therapy respectively. 19 patients got no CR were bridged to CD19 chimeric antigen receptor (CAR)-T cell therapy, while the other 6 patients received additional salvage chemotherapy. In the CAR-T cohort, the ORR was 89.5% (95%CI: 67.0%~98.2%) and CR was 57.9% (95%CI: 34.5%~78.9%), the median PFS was 14 months (95% CI: 5.2-37.9) and median OS was 27.7 months (95% CI: 10.1- not reached). The CAR-T group was associated with improved overall survival relative to the non-CAR-T group (HR = 0.21, 95% CI: 0.05-0.79, P = 0.02). In the landmark analysis, the survival probability of CART group was 80% at 12 months post-landmark, the non-CAR-T group exhibited an earlier initial drop with survival decreasing to 57.1% at 12 months.
Conclusion: Zanubrutinib-combined therapy was effective and safe for the treatment of heavily treated patients with non-GCB DLBCL. It offers a promising treatment option and serving as an effective bridge to CAR-T therapy, with manageable toxicity. Future prospective studies with larger cohorts are needed to validate these findings.

Keywords:  BTK inhibitor; CAR-T therapy; non-GCB DLBCL; relapsed or refractory DLBCL; zanubrutinib-combined therapy

DOI:  https://doi.org/10.3389/fimmu.2026.1806191
JAMA. 2026 Apr 22.

Tucidinostat Plus R-CHOP vs R-CHOP in MYC/BCL2 Double-Expressor Diffuse Large B-Cell Lymphoma: A Randomized Clinical Trial.

Peng-Peng Xu, Yu-Qin Song, Jian-Zhen Shen, Qing-Qing Cai, Hui Zhou, Li-Ling Zhang, Ying Xiang, Xiu-Hua Sun, Wei Yang, Zhi-Hua Yao, Hong-Mei Jing, Shu-Juan Wen, Jie Jin, Hong-Wei Xue, Hong Cen, Kai-Yang Ding, Zheng-Ming Jin, Li-Hong Liu, Xiao-Jing Xing, Lan-Fang Li, Ming Hou, Lin Liu, Ming-Zhi Zhang, Wen-Yu Li, Ou Bai, Ru Feng, Zun-Min Zhu, Hui-Jing Wu, Li-Ping Su, Li Gao, Fei Li, Wen-Rong Huang, Peng Liu, Xiao-Jing Yan, Ying Zhao, Hang Su, Xie-Lan Zhao, Rong Fu, Hong Liu, Wen-Yu Shi, Hui-Zhi Li, Bo Chen, Zhi-Qiang Ning, Jun Zhu, Wei-Li Zhao.

Importance: Epigenetic dysregulation is associated with the pathogenesis and progression of diffuse large B-cell lymphoma (DLBCL). MYC/BCL2 double-expressor lymphoma (DEL), a distinct population of DLBCL defined by MYC and BCL2 coexpression, refers to poor prognosis after standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy. Tucidinostat (or chidamide), an oral, selective histone deacetylase inhibitor, has shown promising activity in DEL.
Objective: To evaluate efficacy and safety of tucidinostat plus R-CHOP vs R-CHOP alone as first-line treatment for patients with DEL.
Design, Setting, and Participants: This randomized, double-blind, placebo-controlled phase 3 trial enrolled patients from May 21, 2020, through July 25, 2022, with follow-up to June 26, 2025. The trial was conducted at 40 study centers in China; a total of 423 eligible patients were enrolled.
Interventions: Patients were randomly assigned in a 1:1 ratio to receive oral tucidinostat (20 mg on days 1, 4, 8, and 11 of each 21-day cycle) or matching placebo, plus 6 cycles of R-CHOP. Patients with a complete response after combination therapy received either tucidinostat or placebo maintenance up to 24 weeks.
Main Outcomes and Measures: The primary end point was event-free survival. Secondary end points included complete response rate, progression-free survival, disease-free survival, overall survival, and tolerability.
Results: Among 423 patients randomized (median age, 63 years; 47.5% male), the median follow-up duration from randomization was 41.3 months. The tucidinostat group demonstrated a 28% lower risk of disease progression, relapse after complete response, death, or initiation of new therapy for residual disease compared with the placebo group (stratified hazard ratio, 0.72 [95% CI, 0.54-0.96]; P = .02), with a 2-year event-free survival rate of 60.3% vs 50.5%, respectively. The complete response rate was 73.0% vs 61.8% (difference, 11.1% [95% CI, 2.3%-20.0%]), respectively. Increased toxicity associated with treatment was observed in the tucidinostat group but generally manageable with supportive care.
Conclusions and Relevance: Tucidinostat plus R-CHOP significantly improved event-free survival, with manageable toxicity in patients newly diagnosed with DEL. This trial is the first to demonstrate the benefit of an epigenetic modulator in DLBCL, offering a new first-line therapeutic approach dually targeting MYC and BCL2 oncoprotein for this high-risk population.
Trial Registration: ClinicalTrials.gov Identifier: NCT04231448.

DOI: https://doi.org/10.1001/jama.2026.4199
J Clin Lab Anal. 2026 Apr 20. e70229

Exportin 1 Inhibitor Combined With Venetoclax Induces Apoptosis in Myelodysplastic Syndrome by Mitochondria-Induced Apoptosis Pathway.

Xiaohan Liu, Lei Huang, Junzhu Wang, Yixuan Guo, Hongli Shen, Xianghong Zhao, Lanzhu Yue, Zhaoyun Liu, Rong Fu.

   BACKGROUND: Myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies that pose a serious health threat. Current therapies include symptomatic treatments for low-risk and hypomethylating agents for high-risk MDS. However, many patients develop resistance to hypomethylating drugs. (Exportin 1) XPO1 inhibition has shown efficacy in inducing tumor cell death by blocking the nuclear export of oncogenes; nevertheless, the role of XPO1 inhibition in MDS remains unexplored.
METHODS: We investigated the role of XPO1 in the pathogenesis of MDS by analyzing XPO1 expression in MDS patients with different risk stratification and healthy controls in the GEO database, and evaluated the effects of the XPO1 inhibitor Selinexor on the proliferation and apoptosis of MDS cells and its mechanism by CCK-8, EdU, flow cytometry, and immunofluorescence. The effects of Selinexor on the proliferation and apoptosis of MDS cells, its mechanism, and its synergistic effect with Bcl-2 inhibitor Venetoclax were evaluated.
RESULTS: We found that XPO1 may have an important role in the development of MDS, and Selinexor induced apoptosis and inhibited the proliferation of MDS cells by inhibiting the nuclear export of p53. Drug combination index assays showed that Selinexor was able to synergize with Venetoclax. The combination of the two resulted in the inhibition of XPO1, which could increase ROS levels in MDS cells and activate mitochondria-mediated apoptotic pathways in cells after inducing elevated MOMP.
CONCLUSION: Our study found that inhibition of XPO1 is a promising modality in the treatment of MDS, especially when combined with Venetoclax, which could be a potential target for MDS therapy.

Keywords:  Bcl‐2; MDS; Venetoclax; XPO1; apoptosis

DOI:  https://doi.org/10.1002/jcla.70229
Clin Lymphoma Myeloma Leuk. 2026 Mar 27. pii: S2152-2650(26)00094-7. [Epub ahead of print]

Seven-day Venetoclax Combined With Dose-adjusted Intensive Chemotherapy as Induction Treatment in Newly Diagnosed Acute Myeloid Leukemia.

Ting Liu, Xingli Zhao, Xiaohui Suo, Guanchen Bai, Yanliang Bai, Weihua Zhao, Hongling Peng, Fang Zheng, Dongmei Wang, Liyun Zhao, Jie Liu, Ling Li, Xinxiao Lu, Congcong Zhang, Sifeng Gao, Zeyan Shi, Yunya Luo, Xuemei Zhao, Yaxian Tan, Zeping Zhou, Pengxiang Guo, Yingchang Mi, Kaiqi Liu.

  While venetoclax (VEN) combined with intensive chemotherapy (IC) has demonstrated efficacy in newly diagnosed acute myeloid leukemia (AML), the optimal duration of VEN administration remains uncertain, leading to variability in its application during induction therapy. Herein, we reported the data of 259 ND AML patients who received 7-day VEN combined with dose-adjusted IC (DA, HAA, or HAD) as induction treatment, to further validate the efficacy and explore the safety of this combination. This study evaluated a truncated 7-day VEN regimen combined with dose-adjusted IC (DA, HAA, or HAD) as induction therapy. The patients included in this study were derived from 2 clinical trials (VEN+DA: ChiCTR2200061524; VEN+HAA: NCT05893472) and 1 retrospective study (VEN+HAD). All induction regimens include a 7-day oral administration of VEN, in combination with either DA, HAA, or HAD regimen. The composite complete remission rate was 90.3%, with a minimal residual disease (MRD) negativity rate of 92.2% as assessed by flow cytometry. After a median follow-up of 18 months, the median overall survival and event-free survival (EFS) were not reached. The estimated 24-month OS, EFS, and relapse-free survival (RFS) rates for the entire cohort were 72.9%, 69.3%, and 70.2%, respectively. No significant differences in survival outcomes were observed among the 3 treatment regimens (OS: P = .68; EFS: P = .73; RFS: P = .34). The median time of the absolute neutrophil count recovered to≥ 0.5 × 109/L and the platelet count to≥ 30 × 109/L after induction therapy was 14 (range: 5-52) days and 13 (range: 4-63) days, respectively. In conclusion, a 7-day VEN schedule maintains high efficacy while potentially reducing myelosuppressive risks of longer regimens.

Keywords:  AML; Induction Treatment; Intensive chemotherapy; Untreated; VEN

DOI:  https://doi.org/10.1016/j.clml.2026.03.017
Int J Hematol. 2026 Apr 22.

Philadelphia chromosome-negative but BCR::ABL1-positive acute lymphoblastic leukemia: a real-world multicenter cohort study.

Shota Yokoyama, Masahiro Onozawa, Hiroyuki Kimura, Takahide Ara, Jun Nagai, Shota Yoshida, Naoki Miyashita, Toshihiro Matsukawa, Hideki Goto, Shinsuke Hirabayashi, Minoru Kanaya, Akio Mori, Daisuke Hidaka, Junichi Hashiguchi, Kentaro Wakasa, Makoto Ibata, Yukari Takeda, Takuto Miyagishima, Satoshi Yamamoto, Katsuya Fujimoto, Toma Suzuki, Tomoyuki Saga, Hajime Sakai, Yasutaka Kakinoki, Tatsuo Oyake, Takeshi Kondo, Takanori Teshima.

  Chronic myelogenous leukemia that carries the BCR::ABL1 fusion gene without cytogenetically detectable Philadelphia (Ph) chromosomes is termed masked Ph. However, the prevalence and clinical relevance of masked Ph in acute lymphoblastic leukemia (ALL) remain unclear. Using the Hokkaido Leukemia Net real-world multicenter cohort, we analyzed 160 B-cell ALL patients diagnosed between 2017 and 2024 with available cytogenetic and molecular data. Among 92 BCR::ABL1-positive cases, 19 (20.7%) lacked a cytogenetically visible Ph chromosome and were classified as masked-Ph ALL. Compared with Ph + ALL, masked-Ph patients were older and had lower white blood cell counts and bone marrow blast percentages at diagnosis. Most BCR::ABL1-positive patients received tyrosine kinase inhibitors (TKIs) during induction, resulting in comparable complete remission rates and similar overall survival between masked-Ph and Ph + ALL; both groups showed superior outcomes compared with BCR::ABL1-negative ALL. The number of metaphases analyzed by G-banding was significantly lower in masked-Ph ALL, suggesting underdetection by conventional cytogenetics. One case exhibited an atypical FISH pattern consistent with a cryptic microinsertion. These findings indicate that masked-Ph ALL is relatively common and may be overlooked without molecular testing, underscoring the importance of incorporating RT-PCR and FISH at diagnosis.

Keywords:  ALL; Cryptic insertion; Hokkaido leukemia net; Masked Ph

DOI:  https://doi.org/10.1007/s12185-026-04212-3
Eur J Haematol. 2026 Apr 19.

From Time-Limited Therapy to Treatment-Free Observation: The Evolving Role of MRD in CLL Management.

Enrica Antonia Martino, Santino Caserta, Ernesto Vigna, Antonella Bruzzese, Maria Eugenia Alvaro, Nicola Amodio, Eugenio Lucia, Virginia Olivito, Caterina Labanca, Francesco Mendicino, Mamdouh Skafi, Valter Gattei, Fortunato Morabito, Massimo Gentile.

  The integration of measurable residual disease (MRD) into the management of chronic lymphocytic leukemia (CLL) has emerged as a major advance in risk stratification and trial design, particularly in the context of time-limited, targeted regimens. High-sensitivity MRD assessment, enabled by multicolor flow cytometry, allele-specific oligonucleotide PCR, and next-generation sequencing (NGS), provides a robust, quantifiable measure for depth of remission and long-term outcomes. Landmark trials-including CLL14, MURANO, CAPTIVATE, and GLOW-have consistently demonstrated that achieving undetectable MRD (uMRD) strongly predicts prolonged progression-free survival (PFS) and overall survival (OS), within a range of chemoimmunotherapy and venetoclax-based time-limited regimens. In selected clinical trials, MRD assessment has been prospectively incorporated into strategies exploring time-limited therapy and MRD-adapted discontinuation, although routine MRD-guided decision-making in clinical practice remains investigational. CLL research is increasingly focused on treatment-free observation in select patients achieving deep and sustained remissions, with MRD playing a central prognostic role. Emerging technologies, including circulating tumor DNA (ctDNA) monitoring and artificial intelligence (AI)-driven predictive modeling, promise to further refine risk stratification and personalize therapy. This review summarizes the current evidence supporting MRD as a prognostic biomarker and clinical trial endpoint, discusses investigational MRD-adapted strategies, and outlines future directions-including ctDNA and AI-based tools-that may ultimately support more individualized treatment duration and treatment-free observation in CLL.

Keywords:  Bruton tyrosine kinase inhibitors; artificial intelligence; chronic lymphocytic leukemia; circulating tumor DNA; minimal residual disease; treatment‐free observation; undetectable MRD; venetoclax

DOI:  https://doi.org/10.1111/ejh.70200
Blood Neoplasia. 2026 May;3(2): 100218

Pharmacological boosting of azacitidine/venetoclax in acute myeloid leukemia.

Niels Westra, Elena Ropero Cerro, Edwin Schilder, Marjolijn N Lub-de Hooge, Daan J Touw, Jos G W Kosterink, Dana A Chitu, Emanuele Ammatuna, Saskia K Klein, Peter E Westerweel, Marloes Cuijpers, Marjan Cruijsen, Maarten M F Corsten, Canan Alhan, Lidwine Tick, Jan Jacob Schuringa, Gerwin Huls, Carolien M Woolthuis, Thijs H Oude Munnink.

Azacitidine/venetoclax is the standard treatment for patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy. Cytochrome P450 3A4 (CYP3A4) is the major metabolizing enzyme for venetoclax, and its inhibition can boost venetoclax. In the HOVON 171 phase 2 trial, patients with AML were treated with azacitidine/venetoclax/cobicistat. This 2-stage, open-label, multicenter phase 2 trial included a crossover run-in phase followed by an ongoing extension phase. In cycle 1, patients received standard-dose azacitidine/venetoclax. In cycle 2, cobicistat was added, and venetoclax was reduced to 50 mg. The primary end point was pharmacokinetic equivalence, defined as 90% confidence interval (CI) of geometric mean ratios (GMRs) >0.8 for area under the curve over 24 hours (AUC0-24h) and maximum plasma concentration (Cmax). Polymorphisms in genes encoding for CYP enzymes were determined. In vitro assays were performed to assess cobicistat's impact on the antileukemic effect of azacitidine/venetoclax in AML cell lines. In 13 evaluable patients, cobicistat-boosted venetoclax at 50 mg achieved higher exposure than standard 400-mg dosing. GMRs were 2.0 (90% CI, 1.4-2.8) for AUC0-24h and 1.4 (90% CI, 1.0-2.0) for Cmax. In the intention-to-treat population, 65% achieved complete remission (CR) or CR with incomplete hematologic recovery. Interpatient variability in venetoclax exposure because of CYP3A4 polymorphisms was reduced by cobicistat. No unexpected toxicities were observed. In in vitro, cobicistat enhanced azacitidine/venetoclax antileukemic effects. In conclusion, cobicistat enhances and optimizes venetoclax exposure, enabling an eightfold dose reduction while maintaining efficacy. The potentiated antileukemic activity positions cobicistat as a promising complementary agent in AML therapy. This trial was registered at www.clinicaltrials.gov as NCT06014489.

DOI: https://doi.org/10.1016/j.bneo.2026.100218
Ann Hematol. 2026 Apr 22. pii: 262. [Epub ahead of print]105(5):

First-line Polatuzumab vedotin plus R-CHP in primary mediastinal B-cell lymphoma: A real-world study bridging the gap of the POLARIX trial.

Xue Yang, Yuhong Ren, Luya Cheng, Yalan Liu, Jiamei Yao, Hui Tan, Peng Liu.



Keywords:  Frontline therapy; Polatuzumab vedotin; Primary mediastinal B-cell lymphoma

DOI:  https://doi.org/10.1007/s00277-026-07024-x