Journal of Clinical Oncology最新文献

{"title":"Assessing Clinical Utility of Datopotamab Deruxtecan Versus Chemotherapy for Breast Cancer.","authors":"Xuan Wang, Ethan B Ludmir, Lee-Jen Wei","doi":"10.1200/JCO-24-02207","DOIUrl":"10.1200/JCO-24-02207","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2136-2137"},"PeriodicalIF":42.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypofractionated, Dose-Escalated Radiation Versus Conventionally Fractionated Radiation for Localized Prostate Cancer: Long-Term Update of a Phase III, Prospective, Randomized Controlled Trial.","authors":"Comron Hassanzadeh, Deborah Kuban, Sarah Pasyar, Roland Bassett, Patricia Troncoso, Maheen Ansari, Pamela Schlembach, Sean McGuire, Quynh Nguyen, Steven Frank, Henry Mok, Osama Mohamad, Ryan Park, Chad Tang, Weiliang Du, Rajat Kudchadker, Seungtaek Choi, Karen Hoffman","doi":"10.1200/JCO-24-02057","DOIUrl":"10.1200/JCO-24-02057","url":null,"abstract":"<p><p>The MD Anderson dose-escalated, hypofractionated prostate radiation study was a phase III randomized trial comparing conventionally fractionated intensity-modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) with dose-escalated, hypofractionated intensity-modulated radiation (HIMRT, 72 Gy in 2.4-Gy fractions) in patients with localized prostate cancer, predominantly low-risk and intermediate-risk disease. The initial publication highlighted statistically fewer treatment failures in the HIMRT arm. We present long-term updated 13-year outcomes to determine whether cancer control benefit was maintained and to evaluate distant metastases post hoc. With a median follow-up of 13.2 years (IQR, 8.8-15.9 years), treatment failure occurred less frequently in men undergoing HIMRT (n = 13) compared with those undergoing CIMRT (n = 22), although the difference no longer meets statistical significance (<i>P =</i> .08). Distant metastases were rare, and no statistically significant difference was noted (<i>P</i> = .2). There remained no statistically significant difference in late GI 2+ (10-year 10% HIMRT <i>v</i> 4% CIMRT, <i>P</i> = .09) or genitourinary grade 2+ toxicity (10-year 26% <i>v</i> 23%, <i>P</i> = .5).</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2044-2048"},"PeriodicalIF":42.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Outcomes After Transoral Robotic Surgery for Oropharyngeal Carcinoma: Reflections on the ASCO Guideline.","authors":"Amir H Safavi, Nadeem Riaz, Eric J Sherman, Richard J Wong, Nancy Y Lee","doi":"10.1200/JCO-25-00654","DOIUrl":"https://doi.org/10.1200/JCO-25-00654","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500654"},"PeriodicalIF":42.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Optimizing Outcomes After Transoral Robotic Surgery for Oropharyngeal Carcinoma: Reflections on the ASCO Guideline.","authors":"F Christopher Holsinger, Nofisat Ismaila, Jamie A Ku","doi":"10.1200/JCO-25-00993","DOIUrl":"https://doi.org/10.1200/JCO-25-00993","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500993"},"PeriodicalIF":42.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glofitamab Combined With Pola-R-CHP or R-CHOP as First Therapy in Younger Patients With High-Risk Large B-Cell Lymphoma: Results From the COALITION Study.","authors":"Adrian Minson, Emma Verner, Pratyush Giri, Jason Butler, Wojt Janowski, Chan Y Cheah, Sumita Ratnasingam, Shu Min Wong, Matthew Ku, Mark Hertzberg, Kirsten Herbert, Nada Hamad, Costas K Yannakou, Fiona Swain, Paul Neeson, Thiago M Steiner, Javad Saghebi, Piers Blombery, Sally M Hunter, Molly Robertson, Lei Shong Lau, Rory Bennett, Sean Harrop, Jing Xie, John F Seymour, Michael J Dickinson","doi":"10.1200/JCO-25-00481","DOIUrl":"https://doi.org/10.1200/JCO-25-00481","url":null,"abstract":"<p><strong>Purpose: </strong>Improved outcomes are needed for patients with high-risk (HR) large B-cell lymphoma (LBCL) who have <50% chance of cure with first-line (1L) R-CHOP chemotherapy. Patients with high burden or rapid progression are often excluded from 1L trials due to screening requirements. We report the investigator-initiated, phase II COALITION trial of the CD20xCD3 bispecific antibody glofitamab combined with R-CHOP or Pola-R-CHP in younger patients with HR features, designed to minimize time between diagnosis and treatment.</p><p><strong>Methods: </strong>Patients age ≤65 years with LBCL and at least one HR feature (international prognostic index [IPI] ≥3, National Comprehensive Cancer Network-IPI ≥4, or rearrangements of <i>MYC</i> and <i>BCL2</i> and/or <i>BCL6</i>) received one cycle of R-CHOP and were randomly assigned to five cycles of Glofit-Pola-R-CHP (n = 40) or Glofit-R-CHOP (n = 40), and two cycles of glofitamab consolidation. Enrollment occurred before or after a cycle of R-CHOP. The primary objective was safety and treatment deliverability. Secondary end points included response rates and survival.</p><p><strong>Results: </strong>Eighty evaluable patients with a median age of 58 years and total metabolic tumor volume of 842 cm³ were included and began treatment a median of 14 days from diagnosis. Over 95% of patients completed all therapy and the median relative dose intensity was >94%. Cytokine release syndrome was observed in 21% of patients, all ≤grade 2 and manageable. Overall and complete response rates were 100% and 98%, respectively. At 20.7-month median follow-up, the estimated 2-year progression-free survival and overall survival were 86% and 92%, respectively.</p><p><strong>Conclusion: </strong>The combination of glofitamab with R-CHOP or Pola-R-CHP is deliverable and results in high rates of durable response in this population of younger patients with high-burden, HR LBCL, supporting its ongoing exploration as a 1L treatment.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500481"},"PeriodicalIF":42.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nivolumab-AVD Versus Brentuximab Vedotin-AVD in Older Patients With Advanced-Stage Classic Hodgkin Lymphoma Enrolled on S1826.","authors":"Sarah C Rutherford, Hongli Li, Alex F Herrera, Michael LeBlanc, Sairah Ahmed, Kelly Davison, Susan K Parsons, Joseph M Unger, Anamarija M Perry, Carla Casulo, Nancy L Bartlett, Joseph M Tuscano, Brian T Hess, Pallawi Torka, Pankaj Kumar, Ryan Jacobs, Joo Y Song, Sharon M Castellino, Brad Kahl, John P Leonard, Sonali M Smith, Jonathan W Friedberg, Andrew M Evens","doi":"10.1200/JCO-25-00204","DOIUrl":"10.1200/JCO-25-00204","url":null,"abstract":"<p><p>Older patients with classic Hodgkin lymphoma (cHL) have inferior survival compared with younger patients. We report a subset analysis of older patients (60 years and older) enrolled in the phase three S1826 trial conducted by SWOG that randomly assigned patients with newly diagnosed advanced-stage (III-IV) cHL to six cycles of nivolumab (N)-AVD or brentuximab vedotin (BV)-AVD. Of 103 enrolled patients 60 years and older, 99 were eligible. At a median follow-up of 2.1 years, the 2-year progression-free survival was 89% after N-AVD (n = 50) and 64% after BV-AVD (n = 49, HR 0.24, 95%CI 0.09-0.63, 1-sided stratified log-rank <i>P</i> = .001). The 2-year OS was 96% with N-AVD versus 85% with BV-AVD (HR 0.16, 95%CI 0.03-0.75 stratified 1-sided log-rank <i>P</i> = .005). Six cycles were delivered without dose reduction in 69% on N-AVD and 26% on BV-AVD; 55% discontinued BV, and 14% discontinued nivolumab. The nonrelapse mortality was 16% with BV-AVD and 6% with N-AVD. Despite more neutropenia with N-AVD, febrile neutropenia, sepsis, and infections were higher with BV-AVD, as was peripheral neuropathy. Patient-reported outcomes of key adverse events confirmed the improved toxicity profile of N-AVD over BV-AVD. N-AVD was better tolerated and more effective than BV-AVD and is therefore a new standard of care for older patients with advanced-stage cHL fit for anthracycline-based combination therapy.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500204"},"PeriodicalIF":42.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis After Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation.","authors":"Monzr M Al Malki, Stephanie Bo-Subait, Brent Logan, Janelle Olson, Jianqun Kou, Sarah Smith, Erin Leckrone, Juan Wu, Heather E Stefanski, Jeffery J Auletta, Stephen R Spellman, Craig Malmberg, Medhat Askar, Rachel Cusatis, Brian C Shaffer, Dipenkumar Modi, Farhad Khimani, Mahasweta Gooptu, Mehdi Hamadani, Abeer Madbouly, Martin Maiers, Stephanie Fingerson, Rachel Cook, Karen Ballen, Alison Loren, Karilyn Larkin, Sally Arai, Muna Qayed, Sung Won Choi, Larisa Broglie, Bronwen E Shaw, Steven Michael Devine, Antonio Martin Jimenez Jimenez","doi":"10.1200/JCO-25-00856","DOIUrl":"10.1200/JCO-25-00856","url":null,"abstract":"<p><strong>Purpose: </strong>Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for advanced hematologic malignancies. HSCT using human leukocyte antigen (HLA)-mismatched donors is historically associated with inferior survival. Patients from underrepresented racial and ethnic groups more frequently rely on HLA-mismatched donors. We hypothesized that post-transplant cyclophosphamide (PTCy) based graft versus host disease (GVHD) prophylaxis would improve outcomes for HSCT recipients using peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors (MMUDs) by reducing the risk of GVHD.</p><p><strong>Methods: </strong>This phase II, nonrandomized, multicenter trial assessed PBSCs in the setting of a GVHD prophylaxis regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil in two adult strata: myeloablative conditioning (MAC) and reduced-intensity or nonmyeloablative (RIC/NMA) conditioning before HSCT from a MMUD. The primary objective was to estimate 1 year overall survival (OS) for each stratum. Key secondary end points included incidences of acute and chronic GVHD.</p><p><strong>Results: </strong>A total of 145 patients enrolled, with 59% self-identifying within an underrepresented group. The 1 year OS was 83.8% (95% CI, 73.1% to 90.4%) for MAC and 78.6% (95% CI, 67% to 86.5%) for RIC/NMA. Incidences of grades III to IV acute GVHD at 6 months were 8% (95% CI, 3.2 to 15.6) for MAC and 10% (95% CI, 4.4 to 18.4) for RIC/NMA. Moderate/severe chronic GVHD at 1 year was 10.3% (95% CI, 4.4 to 18.9) for MAC and 8.6% (95% CI, 3.5 to 16.6) for RIC/NMA. 32% of patients whose donors matched at fewer than seven of eight HLA alleles had similar OS compared with those with donor matched at seven of eight alleles.</p><p><strong>Conclusion: </strong>PTCy-based GVHD prophylaxis after MMUD HSCT with PBSC grafts results in favorable 1 year OS. Using MMUDs expands donor availability to all patients regardless of ancestry (ACCESS; ClinicalTrials.gov identifier: NCT04904588).</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500856"},"PeriodicalIF":42.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adoptive Cell Transfer of Tumor-Infiltrating Lymphocytes for Metastatic Acral Lentiginous Melanoma.","authors":"Paul H McClelland, Shirley K Nah, Alexandra M Gustafson, Aaron J Dinerman, Bradley S White, Billel Gasmi, Donald E White, Sivasish Sindiri, Jared J Gartner, Todd D Prickett, Paul F Robbins, Maria R Parkhurst, Hyunmi Halas, Mei Li M Kwong, Stephanie L Goff, James C Yang, Steven A Rosenberg, Nicholas D Klemen","doi":"10.1200/JCO-24-02348","DOIUrl":"https://doi.org/10.1200/JCO-24-02348","url":null,"abstract":"<p><strong>Purpose: </strong>Acral lentiginous melanoma is a subtype of cutaneous melanoma arising from palmar, plantar, or subungual skin. These tumors are characterized by aggressive biology, a low tumor mutational burden (TMB), and diminished sensitivity to immune checkpoint blockade. It is unknown whether adoptive cell transfer of tumor-infiltrating lymphocytes (ACT-TIL) has efficacy in patients with acral melanoma.</p><p><strong>Methods: </strong>We analyzed prospectively collected data from 442 patients with metastatic cutaneous melanoma who were treated on clinical trials of ACT-TIL at a single institution between 1999 and 2018. Although blinded to treatment outcome and genomic data, we retrospectively identified patients who had acral subtype on the basis of clinicopathologic data available at the time of diagnosis. We then evaluated the ACT-TIL treatment outcomes of patients with acral melanoma and compared them with contemporaneously treated patients with nonacral melanoma.</p><p><strong>Results: </strong>Out of 442 included patients, 30 (7%) had acral melanoma while 412 (93%) had nonacral melanoma. Cohorts had similar clinical characteristics, protocol enrollment, and treatment-related factors. The objective response rate to ACT-TIL in patients with acral and nonacral melanomas was 43% and 40%, respectively (<i>P</i> = .87), with 3% and 16% having complete responses (CRs; <i>P</i> = .07). Median progression-free survival was 3.5 and 4.1 months (<i>P</i> = .40) and median overall survival was 13 and 17 months (<i>P</i> = .79), respectively. Acral melanomas had lower TMB and ultraviolet mutational signature scores than nonacral melanomas.</p><p><strong>Conclusion: </strong>ACT-TIL can mediate objective responses in patients with metastatic acral melanoma, and outcomes in patients with acral disease were unexpectedly comparable with those of contemporaneously treated patients with nonacral cutaneous melanoma. Further research is necessary to understand the immunologic basis of responses to ACT-TIL in acral melanoma and to increase the frequency of CRs.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402348"},"PeriodicalIF":42.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overall Survival After Allogeneic Transplantation in Advanced Cutaneous T-Cell Lymphomas (CUTALLO): A Propensity Score-Matched Controlled Prospective Study.","authors":"Adèle de Masson, Marie Beylot-Barry, Caroline Ram-Wolff, Jean-Baptiste Mear, Stéphane Dalle, Jacques Rouanet, Saskia Ingen-Housz-Oro, Corentin Orvain, Julie Abraham, Olivier Dereure, Amandine Charbonnier, Jérôme Cornillon, Christine Longvert, Stéphane Barete, Serge Boulinguez, Ewa Wierzbicka-Hainaut, François Aubin, Marie-Thérèse Rubio, Marc Bernard, Aline Schmidt-Tanguy, Roch Houot, Anne Pham-Ledard, David Michonneau, Hélène Labussière-Wallet, Jean-David Bouaziz, Florent Grange, Hélène Moins-Teisserenc, Katayoun Jondeau, Samia Mourah, Maxime Battistella, Etienne Daguindau, Michael Loschi, Alexandra Picard, Nathalie Franck, Natacha Maillard, Anne Huynh, Stéphanie Nguyen, Ambroise Marçais, Guillaume Chaby, Patrice Ceballos, Yannick Le Corre, Sébastien Maury, Jacques-Olivier Bay, Henri Adamski, Emmanuel Bachy, Edouard Forcade, Gérard Socié, Martine Bagot, Sylvie Chevret, Régis Peffault de Latour","doi":"10.1200/JCO-25-00183","DOIUrl":"https://doi.org/10.1200/JCO-25-00183","url":null,"abstract":"<p><p>Cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and sometimes fatal diseases. Patients presenting with advanced-stage CTCL usually exhibit poor long-term survival outcomes. Only very few treatments have improved progression-free survival (PFS) in advanced CTCL, and no treatment has increased overall survival (OS). In 2023, the results of the CUTALLO trial supported the hypothesis that hematopoietic stem-cell transplantation (HSCT) was associated with significantly longer PFS as compared with standard-of-care treatment among advanced-stage patients although HSCT did not significantly affect OS. We provide herein the final OS data pertaining to the same patient population after a longer median follow-up of 38.9 months. Of the 99 patients included in the analysis, 55 (56%) were assigned to the HSCT group, whereas 44 (44%) were allocated to the non-HSCT group. The updated survival analysis reported that 16 of 55 patients (29%) in the HSCT group and 22 of 44 patients (50%) in the non-HSCT group died. The median OS was not reached in the HSCT group and 51.5 months (95% CI, 26.9 to 51.5) in the non-HSCT group (hazard ratio, 0.40 [95% CI, 0.20 to 0.80]). Compared with the standard of care for advanced CTCL, after extended follow-up, allogeneic HSCT was associated with significantly longer OS.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500183"},"PeriodicalIF":42.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Frontline Triplet Regimens With a Hypomethylating Agent, Venetoclax, and Isocitrate Dehydrogenase Inhibitor for Intensive Chemotherapy-Ineligible Patients With Isocitrate Dehydrogenase-Mutated AML.","authors":"Courtney D DiNardo, Jennifer Marvin-Peek, Sanam Loghavi, Koichi Takahashi, Ghayas C Issa, Wei-Ying Jen, Naval G Daver, Patrick K Reville, Nicholas J Short, Koji Sasaki, Jillian K Mullin, Corey A Bradley, Gautam Borthakur, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Hussein A Abbas, Danielle E Hammond, Fadi Haddad, Guillermo Montalban Bravo, Kelly S Chien, Musa Yilmaz, Steven M Kornblau, Elias Jabbour, Farhad Ravandi, Tapan Kadia, Guillermo Garcia-Manero, Marina Y Konopleva, Hagop M Kantarjian","doi":"10.1200/JCO-25-00640","DOIUrl":"10.1200/JCO-25-00640","url":null,"abstract":"<p><strong>Purpose: </strong>The development of targeted therapeutics has revolutionized treatment for elderly patients with AML. Two doublet regimens are approved in the frontline setting for intensive chemotherapy (IC)-ineligible AML: venetoclax (VEN) in combination with hypomethylating agent (HMA) therapy and azacitidine (AZA) plus ivosidenib (IVO) specifically for <i>IDH1</i>-mutated AML. Although both regimens have improved AML outcomes, most patients will either not respond to frontline therapy or relapse, with dismal salvage outcomes.</p><p><strong>Methods: </strong>We herein report on 60 newly diagnosed IC-ineligible patients treated at our institution with triplet regimens for isocitrate dehydrogenase (<i>IDH</i>)-mutant AML. Patients received either AZA + VEN + IVO on NCT03471260 (<i>IDH1</i>-mutated patients only) or oral decitabine + VEN + IVO/enasidenib on NCT04774393 (arms for <i>IDH1-</i> and <i>IDH2</i>-mutant disease, respectively).</p><p><strong>Results: </strong>The triplet regimens were well tolerated with low early mortality (n = 1 [2%] in 60 days) and a similar safety profile to HMA + VEN and isocitrate dehydrogenase inhibitor doublet regimens. The composite complete remission rate (CRc) was 92% (55/60), with an overall response rate of 95% (57/60). With a median follow-up of 27.4 months, the median overall survival (OS) has not yet been reached. The 2-year OS was 69% with a 2-year cumulative incidence of relapse of 24%. Patients with treated-secondary AML (tsAML) experienced inferior outcomes with a CRc of 71% (12/17) and a 2-year OS of 34%; the 2-year OS was 84% in patients without tsAML. Nineteen patients (32%) transitioned to stem cell transplant, and 51% remain on study.</p><p><strong>Conclusion: </strong>Given the excellent outcomes of IDH-triplet therapy for newly diagnosed, IC-ineligible <i>IDH</i>-mutant AML, further prospective studies comparing IDH-triplet versus IDH-doublet regimens are warranted.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500640"},"PeriodicalIF":42.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}