Clinical Lymphoma, Myeloma & Leukemia最新文献

{"title":"Safe Integration of Radiation Therapy With Bispecific Antibodies in Relapsed/Refractory B-cell Lymphomas","authors":"Jonathan A. Baron,&nbsp;Monica Chelius,&nbsp;Gurbani Singh,&nbsp;Michael D. Schad,&nbsp;Melanie Berger,&nbsp;Emeline R. Chong,&nbsp;Colin J. Thomas,&nbsp;Jordan S. Carter,&nbsp;Michael R. Cook,&nbsp;Sunita D. Nasta,&nbsp;Daniel J. Landsburg,&nbsp;Stefan K. Barta,&nbsp;Jakub Svoboda,&nbsp;Stephen J. Schuster,&nbsp;Nikhil Yegya-Raman,&nbsp;Michael J. LaRiviere,&nbsp;John P. Plastaras,&nbsp;Elise A. Chong,&nbsp;Harper Hubbeling","doi":"10.1016/j.clml.2026.07.004","DOIUrl":"10.1016/j.clml.2026.07.004","url":null,"abstract":"<div><h3>Introduction/Background</h3><div>T-cell–engaging bispecific antibodies (BsAbs) are effective for relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs). Radiation therapy (RT) is increasingly used for palliation or bridging/cytoreduction in patients receiving BsAbs, but data on the safety of RT delivered in close temporal proximity to BsAbs are limited. We report the largest series to date evaluating RT and BsAbs in B-NHL.</div></div><div><h3>Patients and Methods</h3><div>We retrospectively identified patients with B-NHL who received RT ≤ 3 months before, during, or ≤ 3 months after BsAb at a single institution between 2018 and 2024. Timing was categorized as pre-, peri-, or post-BsAb. Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria; other toxicities per CTCAE v5.0. In-field responses were assessed per Lugano criteria.</div></div><div><h3>Results</h3><div>Twenty-nine patients underwent 31 BsAb courses and received RT to 52 sites (50% pre-, 13% peri-, 37% post-BsAb). Common histologies included DLBCL (52%), follicular lymphoma (FL) (26%), and transformed FL (16%). All RT-related toxicities were grade 1 to 2, with no RT-related hospitalizations. CRS occurred in 7 BsAb courses and ICANS in 4, with no apparent relationship to RT timing or dose. Early post-RT lymphopenia was common across groups, but its frequency and severity did not differ by RT timing. Among 44 evaluable lesions, the in-field overall response rate was 84% (CR 45%, PR 39%).</div></div><div><h3>Conclusion</h3><div>RT before, during, or after BsAb was well tolerated, without apparent additive toxicity, and achieved high in-field response rates, supporting the safe integration of RT with BsAbs for R/R B-NHL.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 10","pages":"Pages 698-705.e1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment Modalities and the Impact of Granulocyte Colony-Stimulating Factor in AML Patients Treated With Venetoclax and Azacitidine: A DATAML Registry Study","authors":"Léopoldine Lapierre,&nbsp;Lucie Laemmel,&nbsp;Emilie Bérard,&nbsp;Lucie Rigolot,&nbsp;Audrey Bidet,&nbsp;Jules Higué,&nbsp;Anne Banos,&nbsp;Guillaume Béziat,&nbsp;Ramzi Jeddi,&nbsp;Benoit Branco,&nbsp;Claire Calmettes,&nbsp;Noémie Gadaud,&nbsp;Martin Gauthier,&nbsp;Leila Ghenim,&nbsp;Gaelle Laboure,&nbsp;Clémentine Salvado,&nbsp;Reza Tabrizi,&nbsp;Joséphine Thomazeau,&nbsp;Willy Vaillant,&nbsp;Suzanne Tavitian,&nbsp;Christian Récher","doi":"10.1016/j.clml.2026.07.007","DOIUrl":"10.1016/j.clml.2026.07.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Azacitidine-venetoclax (AZA-VEN) has become a standard treatment in older or chemotherapy-ineligible AML patients. While the registration trial showed a median overall survival (OS) of 14.7 months, most real-world studies have not reproduced this result.</div></div><div><h3>Patients and Methods</h3><div>We analyzed treatment patterns, adverse events, responses and outcomes in 199 patients treated with AZA-VEN in the DATAML registry.</div></div><div><h3>Results</h3><div>The median age was 75.6 years, 48.7% had secondary AML (11% post-MPN); 11.7% had another cancer, and 9% had received AZA for prior myelodysplastic syndrome. Cytogenetic risk was intermediate (55.8%) or adverse (43.7%). The most frequent gene mutations were <em>ASXL1</em> (33%), <em>TET2</em> (27%), <em>TP53</em> (26%), <em>RUNX1</em> (24%) and <em>SRSF2</em> (24%).</div><div>The first cycle was performed on an outpatient basis in 39.4% of patients. The median number of cycles was 4 and 37% received &gt; 6 cycles. Beyond cycle 6, reductions in treatment dose or duration were attributed to VEN in 55% of patients and to AZA for 43%. The complete remission (CR) plus CR with incomplete hematologic recovery (CRi) rate was 58.5%, and day-30 death rate was 3%. Median OS was 8.9 months. mPRS and refined-ELN2024 classifications were significantly associated with response and OS. In CR/CRi patients, G-CSF use was significantly and independently associated with improved OS (median, 10.1 months without versus 20.3 with G-CSF; <em>P</em> = .001). In an external cohort, G-CSF was also associated with a trend towards improved OS.</div></div><div><h3>Conclusion</h3><div>In real-world clinical practice, patients with more severe characteristics are typically selected for AZA-VEN, which could explain suboptimal outcomes. G-CSF should be prospectively explored in AZA-VEN treated patients.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 10","pages":"Pages e1187-e1201.e16"},"PeriodicalIF":4.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Menin–KMT2A Axis in AML: Translating Molecular Insights into Therapeutic Success","authors":"Claudia Simio,&nbsp;Alessandra Vatteroni","doi":"10.1016/j.clml.2026.07.019","DOIUrl":"10.1016/j.clml.2026.07.019","url":null,"abstract":"<div><div>Menin inhibitors (MIs) represent a novel class of targeted agents that disrupt the interaction between the nuclear protein menin and the KMT2A (MLL) complex, thereby interrupting a crucial oncogenic transcriptional program in acute myeloid leukemias (AML) with KMT2A rearrangements and NPM1 mutations. Robust preclinical data have shown that menin inhibition suppresses HOXA/MEIS1 expression, induces differentiation, and reduces the fitness of leukemic cells, including the stem-like compartment. These findings rapidly led to phase I/II clinical trials with oral MIs such as revumenib and ziftomenib, which demonstrated CR+CRh rates of 22% to 23% in refractory/relapsed patients, with conversion to measurable residual disease (MRD) negativity in 61% to 68% of responders and early use as a bridge to allogeneic transplantation. However, the median duration of response remains limited (approximately 4-5 months), suggesting that menin inhibition as monotherapy may be insufficient to ensure durable disease control. Key emerging clinical issues include specific adverse events (QTc prolongation in 12%-44%, differentiation syndrome in 10%-29%), drug–drug interactions mediated by CYP3A4 metabolism, resistance dynamics (on-target mutations in 39% of cases), and the definition of the optimal role in combination with venetoclax, hypomethylating agents, and intensive chemotherapy. This review synthesizes molecular mechanisms, preclinical and clinical data, discusses use within MRD-guided and transplant pathways, and proposes translational priorities for integrating MIs into future therapeutic paradigms, pending confirmation from randomized studies.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 10","pages":"Pages 649-660"},"PeriodicalIF":4.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prognostic Utility of Normal Karyotype Fraction in Acute Myeloid Leukemia","authors":"Ameed Bawwab,&nbsp;Emily C. Zabor,&nbsp;Lana Khatib,&nbsp;Moath Albliwi,&nbsp;John Hanna,&nbsp;Jessica El-Asmar,&nbsp;Daniel P. Nurse,&nbsp;Hasan Abuamsha,&nbsp;Yomna Abu-Farsakh,&nbsp;Asad Rauf,&nbsp;Ahmed Mohamed,&nbsp;Muaz Alsabbagh Alchirazi,&nbsp;Joy Nakitandwe,&nbsp;David S. Bosler,&nbsp;Prerana Bangalore Parthasarathy,&nbsp;Tyler Alban,&nbsp;Akriti G. Jain,&nbsp;John C. Molina,&nbsp;Sophia Balderman,&nbsp;Abhay Singh,&nbsp;Moaath K. Mustafa Ali","doi":"10.1016/j.clml.2026.08.005","DOIUrl":"10.1016/j.clml.2026.08.005","url":null,"abstract":"<div><h3>Background</h3><div>The prognostic significance of the proportion of normal metaphases detected at diagnosis in acute myeloid leukemia (AML) has not been systematically evaluated.</div></div><div><h3>Patients and Methods</h3><div>We conducted a retrospective cohort study of 893 adult AML patients treated at Cleveland Clinic between January 2015 and September 2023 who underwent conventional cytogenetic analysis. Normal karyotype fraction (NKF) was defined as the proportion of normal metaphases among all metaphases analyzed at diagnosis. NKF was evaluated as a continuous measure and categorized using three-group (NKF = 0, 0 &lt; NKF &lt; 1, NKF = 1) and 5-group functional classification systems. Primary outcomes included overall survival (OS), event-free survival (EFS), composite complete remission (CR/CRi), and relapse. Multivariable Cox proportional hazards and logistic regression models were adjusted for established prognostic covariates.</div></div><div><h3>Results</h3><div>NKF demonstrated a bimodal distribution across the cohort. Patients with NKF = 1 achieved the highest CR/CRi rate (64%) and longest median OS (16 months) and EFS (11 months). In multivariable analyses, NKF = 1 was independently associated with improved OS (hazard ratio [HR], 0.77, 95% confidence interval [CI], 0.61-0.97) and EFS (HR, 0.73, 95% CI, 0.58-0.91), and higher odds of achieving CR/CRi (odds ratio 1.72, 95% CI, 1.10-2.70) compared with NKF = 0. EFS was significantly associated with NKF categories in both classification systems (<em>P</em> &lt; .05).</div></div><div><h3>Conclusion</h3><div>NKF is a readily obtainable cytogenetic parameter that was associated with treatment response and survival in this cohort. External validation and prospective studies are warranted to support its use in clinical risk stratification frameworks.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 10","pages":"Pages e1160-e1174"},"PeriodicalIF":4.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geographic Variation and Inequities in Burden and Access to CAR T-Cell Therapies for Multiple Myeloma in the US","authors":"Brandon J. Blue,&nbsp;Andrew K. ElHabr,&nbsp;Benjamin A. Derman,&nbsp;Avik Ray,&nbsp;Jie Ting,&nbsp;Ken Hasegawa,&nbsp;Zizi Elsisi,&nbsp;Kian Farajkhah,&nbsp;Turgay Ayer,&nbsp;Attaya Suvannasankha","doi":"10.1016/j.clml.2026.07.009","DOIUrl":"10.1016/j.clml.2026.07.009","url":null,"abstract":"<div><h3>Background</h3><div>Chimeric antigen receptor (CAR) T-cell therapies offer substantial survival benefits for relapsed and/or refractory multiple myeloma (RRMM). However, access remains limited across the US. We examined geographic variation in MM burden and key drivers of CAR T access disparities to inform targeted strategies to close these gaps.</div></div><div><h3>Patients and Methods</h3><div>Patients with MM and CAR T recipients from January 2021-August 2024 were identified from the Komodo Patient-Level Analytics and Insights Derivative claims database. MM prevalence at the ZIP-3 level came from the US Cancer Statistics database. Drive-times to the nearest authorized treatment center (ATC) for patients with MM and to ATCs for CAR T recipients were calculated and compared nationally and by region.</div></div><div><h3>Results</h3><div>There were 106,593 prevalent patients over the study period. The South had the second highest MM burden (66.1/100,000 people) but the lowest proportion of patients within 1 hour of an ATC (55.7%). CAR T recipients in the South also traveled the longest to their ATC (median, 1.5 hours). Multivariable analysis with socio-economic and demographic covariates indicated that ≥ 2 hour potential drive-time to nearest ATC versus &lt; 1 hour (adjusted odds ratio [or] = 0.43; 95% confidence interval (CI), 0.27-0.69), household income &lt; $50k versus ≥ $100k (or = 0.19; 95% CI, 0.05-0.69), and residence in nonmetropolitan areas versus metropolitan (or = 0.41; 95% CI, 0.28-0.60) were significantly associated with reduced odds of CAR T use.</div></div><div><h3>Conclusions</h3><div>There were substantial geographic and socioeconomic disparities in CAR T access, with long drive‑times, lower household income, and non‑metro residence limiting uptake and underscoring the need for targeted ATC expansion.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 10","pages":"Pages e1202-e1210.e8"},"PeriodicalIF":4.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Observational Study of Patients With Chronic Lymphocytic Leukemia Treated With Fixed Duration Therapy in a 1L Setting in Canada","authors":"Carolyn Owen,&nbsp;Sydney George,&nbsp;Sandra Thibault,&nbsp;Mariet Mathew Stephen,&nbsp;Mackenzie A. Hamilton,&nbsp;Simar Gill,&nbsp;Winson Y. Cheung","doi":"10.1016/j.clml.2026.08.001","DOIUrl":"10.1016/j.clml.2026.08.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Targeted fixed duration (FD) therapies have emerged as new treatment options that have been shown to be highly effective for patients with chronic lymphocytic leukemia (CLL). To date, there is limited Canadian data on the uptake and outcomes of CLL treatment following the approval of FD therapy.</div></div><div><h3>Patients and Methods</h3><div>This study was conducted to evaluate the clinical and demographic characteristics, treatment outcomes, and healthcare resource utilization (HCRU) of CLL patients treated with FD treatments in the 1L setting between 01 January 2010 and 31 December 2023 in Alberta, Canada.</div></div><div><h3>Results</h3><div>In total, 589 patients received therapy for CLL during this time period, and venetoclax plus obinutuzumab (VO) represented the most common therapy from 2021 to 2023. Additionally, patients receiving VO showed the highest survival rates at 12 months (95% confidence interval [CI]) at 97.6% (94.5, 100.0), followed by fludarabine, cyclophosphamide, and rituximab (FCR) at 96.6% (94.0, 99.3).</div></div><div><h3>Conclusion</h3><div>These results highlight the shift in the treatment landscape for CLL with the potential for improved patient outcomes.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 10","pages":"Pages e1229-e1240"},"PeriodicalIF":4.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Deaths in Acute Promyelocytic Leukemia in the Era of All-Trans Retinoic Acid: National Real-World Study in Algeria","authors":"Mohamed-Amine Bekadja,&nbsp;Mohand Tayeb Abad,&nbsp;Mohamed Bradai,&nbsp;Mahdia Saidi,&nbsp;Malika Allouda,&nbsp;Fatiha Grifi,&nbsp;Habiba Mehanaoui,&nbsp;Selma Hamdi,&nbsp;Hakim Hamouda,&nbsp;Meriem Belhani,&nbsp;Nadia Boudjerra,&nbsp;Zohra Kaci,&nbsp;Rose-Marie Hamladji,&nbsp;Redhouane Ahmed-Nacer,&nbsp;Malek Benakli,&nbsp;Hadj Touhami,&nbsp;Djamel Saidi,&nbsp;Reda Messaoudi,&nbsp;Fatima Zohra Ardjoun,&nbsp;Khadidja Djouadi,&nbsp;Soraya Bougherira","doi":"10.1016/j.clml.2026.07.016","DOIUrl":"10.1016/j.clml.2026.07.016","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 10","pages":"Pages e1175-e1177.e2"},"PeriodicalIF":4.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Toxicities of Contemporary Cancer Immunotherapies: A Narrative Review of Immune Checkpoint Inhibitors, Bispecific T-Cell Engagers, and CAR-T Cell Therapies.","authors":"Jean El Cheikh, Bahaa El Deen Wehbeh, Ali Tarhini, Ralf Mansour, Georgio Sayde, Nicole Charbel, Katia Kautaich, Ibrahim Hasan, Marwan M Refaat","doi":"10.1016/j.clml.2026.09.019","DOIUrl":"https://doi.org/10.1016/j.clml.2026.09.019","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs), bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T-cell therapies have produced durable responses across different hematologic malignancies, but each class carries cardiovascular liabilities that differ fundamentally in mechanism, incidence, timing, and mortality risk. A structured narrative review of PubMed/MEDLINE and EMBASE from inception through March 2026 was performed, supplemented by pharmacovigilance data from FAERS and WHO VigiBase, to review and synthesize the available evidence on cardiovascular toxicity and provide a structured comparison of incidence, mechanisms, clinical presentation, outcomes, and monitoring strategies to guide clinical practice. ICI-associated myocarditis is rare (0.06%-1.14%) but carries a case fatality rate approaching 50%, a lethality amplified by combination regimens and obscured by preserved left ventricular ejection fraction in approximately half of presentations. BiTEs may occupy a mechanistically intermediate position: cardiovascular adverse events are reported in 8% to 20% of pharmacovigilance cases, and 83% of these arise without documented concurrent cytokine release syndrome (CRS), implying that their immunopathological profile lies closer to ICI than to CAR-T injury. Bispecific agents are not a homogeneous class: blinatumomab, teclistamab, talquetamab, and elranatamab differ in construct, target antigen, disease setting, CRS frequency, and reported cardiovascular phenotype, and agent-level effects cannot presently be separated from population-level ones. CAR-T cell therapy produces cardiovascular events in up to 19% to 26% of patients, predominantly through IL-6-driven, CRS-coupled hemodynamic injury, with left ventricular dysfunction resolving in the majority following CRS management. Across all 3 classes, foundational clinical trials incorporated no routine cardiac monitoring, current surveillance practices are heterogeneous, and no prospective head-to-head comparative data exist. Each immune therapy class poses a qualitatively distinct cardiac threat at a different point in the treatment course. Risk-adapted surveillance extending beyond the CRS window appears prudent for BiTEs, although this reflects extrapolation rather than validated evidence; serologic and imaging monitoring regardless of systemic symptoms remains essential for ICI recipients; and CRS-guided early intervention is the cornerstone of CAR-T cardiotoxicity management. This review aims to provide clinicians with a comprehensive overview of the cardiovascular toxicities associated with these modern therapies.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Use of Bruton-Tyrosine Kinase Inhibitors in Non-IgM Lymphoplasmacytic Lymphoma: A Retrospective Italian Study.","authors":"Alessandro Noto, Nicolò Danesin, Adalberto Ibatici, Michele Merli, Raffaella Pasquale, Michela Schirru, Emanuele Cencini, Silvia Ferrari, Gloria Margiotta Casaluci, Maura Nicolosi, Marina Deodato, Arianna Zappaterra, Roberto Cairoli, Francesco Piazza, Marzia Varettoni, Alessandra Tedeschi, Anna Maria Frustaci","doi":"10.1016/j.clml.2026.09.018","DOIUrl":"https://doi.org/10.1016/j.clml.2026.09.018","url":null,"abstract":"","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOHO State of the Art Updates and Next Questions | The Evolving AML Treatment Paradigm.","authors":"Elyse A Olesinski, Brandon J Aubrey, Amir T Fathi","doi":"10.1016/j.clml.2026.09.016","DOIUrl":"https://doi.org/10.1016/j.clml.2026.09.016","url":null,"abstract":"<p><p>The treatment paradigm for fit, younger adults with acute myeloid leukemia (AML) is evolving toward the frontline use of lower-intensity, better-tolerated therapies that more effectively target disease biology. For over 45 years, intensive chemotherapy (IC) has endured as the cornerstone of induction therapy for fit AML patients. Clinical outcomes have slowly improved during this time; however, long-term survival remains suboptimal, and IC-related toxicity is significant. For older AML patients, clinical outcomes have been transformed by the introduction of hypomethylating agents in combination with venetoclax (HMA-Ven) because of its potent anti-leukemic activity and improved tolerability. The success of HMA-Ven highlights the importance of rationally designed therapies that exploit leukemia dependencies while minimizing systemic toxicity. We outline the development of IC and HMA-Ven while also describing the first studies to directly compare these distinct modalities in younger patients. We explore growing evidence that guides the use of lower-intensity therapy in younger AML patients who would traditionally receive IC but may achieve favorable outcomes using HMA-Ven. When considering the use of HMA-Ven in younger patients, we highlight several important issues including the need for improved patient selection for HMA-Ven, optimal implementation of HMA-Ven in patients planned for allogeneic stem cell transplant (HCT), evaluation of post-HCT outcomes following induction using HMA-Ven, utilization of measurable residual disease (MRD) during treatment with HMA-Ven, and the prospect of triple combinations incorporating novel targeted agents.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}