Journal of Clinical Oncology最新文献

{"title":"Enfortumab Vedotin: A Promising Therapy for Head and Neck Cancer With Potential Links to Human Papillomavirus.","authors":"Mustafa Yaylalı, Buse Halaç, Bülent Yalçın","doi":"10.1200/JCO-24-02689","DOIUrl":"https://doi.org/10.1200/JCO-24-02689","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402689"},"PeriodicalIF":42.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458244","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: Enfortumab Vedotin: A Promising Therapy for Head and Neck Cancer With Potential Links to Human Papillomavirus.","authors":"Paul L Swiecicki, Emrullah Yilmaz, Ari Joseph Rosenberg, Takao Fujisawa, Justine Yang Bruce, Changting Meng, Michele Wozniak, Yongyun Zhao, Michael Mihm, Jason Kaplan, Seema Gorla, Jessica L Geiger","doi":"10.1200/JCO-25-00028","DOIUrl":"https://doi.org/10.1200/JCO-25-00028","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500028"},"PeriodicalIF":42.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458245","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":"COSMIC-021 Phase Ib Study of Cabozantinib Plus Atezolizumab: Results from the Locally Advanced or Metastatic Urothelial Carcinoma Cohorts.","authors":"Sumanta K Pal, Yohann Loriot, Andrea Necchi, Parminder Singh, Daniel Castellano, Lance Pagliaro, Cristina Suarez, Bradley A McGregor, Ulka N Vaishampayan, Ralph J Hauke, Thomas Powles, Carla M L Van Herpen, Kevin D Courtney, Robert Dreicer, Ramu Sudhagoni, Martin Schwickart, Svetlana Andrianova, Neeraj Agarwal","doi":"10.1200/JCO-24-01675","DOIUrl":"https://doi.org/10.1200/JCO-24-01675","url":null,"abstract":"<p><strong>Purpose: </strong>The COSMIC-021 study assessed the safety and efficacy of cabozantinib plus atezolizumab in advanced solid tumors. Presented here are results from the expansion cohorts with advanced urothelial carcinoma (UC).</p><p><strong>Methods: </strong>This phase Ib study (ClinicalTrials.gov identifier: NCT03170960) enrolled patients with inoperable locally advanced/metastatic UC into four tumor cohorts: first-line cisplatin-eligible (cis-eligible), first-line cisplatin-ineligible (cis-ineligible), previous platinum-containing chemotherapy (previous chemotherapy-treated), and previous immune checkpoint inhibitor (ICI)-treated. Patients received oral cabozantinib 40 mg once daily and intravenous atezolizumab 1,200 mg once every 3 weeks. The primary end point was objective response rate (ORR), as assessed by the investigator per RECIST v1.1 every 6 weeks for 12 months and every 12 weeks thereafter; the secondary end point was safety.</p><p><strong>Results: </strong>A total of 121 patients (previous ICI-treated cohort, n = 31, and each of the other cohorts, n = 30) received study treatment from March 2018 to November 2021. The ORR (95% CI) was 30% (15 to 49) for cis-eligible, 20% (8 to 39) for cis-ineligible, 27% (12 to 46) for previous chemotherapy-treated, and 10% (2 to 26) for previous ICI-treated cohorts. The median progression-free survival (95% CI) was 5.5 (1.6 to 11.6), 5.6 (3.1 to 11.1), 5.4 (1.6 to 7.6), and 3.0 (1.8 to 5.5) months, respectively. Grade 3 or 4 treatment-related adverse events (TRAEs) were experienced by 43%, 67%, 57%, and 45% of patients, respectively. TRAEs led to discontinuation of all treatment components in 17%, 13%, 3%, and 19%, respectively. No grade 5 TRAEs were reported in any cohort.</p><p><strong>Conclusion: </strong>The novel combination of cabozantinib plus atezolizumab exhibited clinical activity in advanced UC that is cis-eligible, cis-ineligible, or previously treated with platinum-containing chemotherapy; clinical activity in previous ICI-treated UC was modest. The toxicity profile was consistent with that previously reported for the combination.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401675"},"PeriodicalIF":42.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449129","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":"Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma.","authors":"Martin F Kaiser, Pieter Sonneveld, David A Cairns, Marc S Raab, Jesús San-Miguel Izquierdo, Rick Zhang, Jorge Acosta, Alessandra Larocca, Rakesh Popat, Cong Li, Marc-A Baertsch, Sarah R Brown, JuanJose Lahuerta Palacios, Anita K Gandhi, Sandrine Macé, Pellegrino Musto, Kwee Yong, Elias K Mai, Franck Dubin, Joan Blade, Andrea Capra, Gordon Cook, Uta Bertsch, María-Victoria Mateos, Mario Boccadoro, Graham H Jackson, Norma C Gutiérrez, Francesca Gay, Niels Weinhold","doi":"10.1200/JCO-24-01253","DOIUrl":"https://doi.org/10.1200/JCO-24-01253","url":null,"abstract":"<p><strong>Purpose: </strong>Survival for patients with multiple myeloma (MM) has improved but outcomes remain heterogeneous. Consistent diagnostic identification of high-risk disease is desirable to address unmet patient need. The aim was to investigate the consistency of association of co-occurrence of high-risk cytogenetic abnormalities (HRCAs) with prognosis in patients with newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM), and across a range of treatment modalities.</p><p><strong>Methods: </strong>A systematic review of randomized controlled trials of MM that reported testing for HRCA between January 1, 2000, and December 9, 2021, was performed. Groups were contacted and asked to locally perform a novel, federated analysis of their data for single hit (one HRCA) and double hit (≥two HRCAs), using a centrally provided algorithm. Analysis results were centrally collated and meta-analyzed to assess the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) for one/≥two HRCAs across patient subgroups using random-effects models.</p><p><strong>Results: </strong>Twenty-four trials including 13,926 patients were included. The median age of participants was 66.5 years (IQR, 59-72) and 56.5% were male (IQR, 52-60). The HR for PFS was 2.28 (95% CI, 2.05 to 2.54) for patients with ≥two HRCAs and 1.51 (95% CI, 1.38 to 1.65) for patients with one HRCA. The HR for OS was 2.94 (95% CI, 2.49 to 3.47) and 1.69 (95% CI, 1.52 to 1.88) for the two subgroups, respectively. In studies initiated since 2015, the effect abides (≥two HRCA PFS, HR, 2.39 [95% CI, 1.96 to 2.91]; OS, 3.10 [95% CI, 2.10 to 4.60]) both for NDMM and RRMM. Heterogeneity related to transplant eligibility and relapsed/refractory status was as expected.</p><p><strong>Conclusion: </strong>The association of ≥two HRCAs with the poorest outcome in NDMM and RRMM, and across treatment modalities, as demonstrated here for the first time to our knowledge, allows for more focused development of novel approaches to these patients with high unmet need.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401253"},"PeriodicalIF":42.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449088","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":"Comparison of Standard-of-Care Idecabtagene Vicleucel and Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma.","authors":"Doris K Hansen, Lauren C Peres, Danai Dima, Alicia Richards, Leyla Shune, Aimaz Afrough, Shonali Midha, Binod Dhakal, Mehmet H Kocoglu, Shebli Atrash, Christopher Ferreri, Omar Castaneda, James A Davis, Evguenia Bhurtel, Joseph McGuirk, Charlotte Wagner, Radhika Bansal, Patrick Costello, Kinaya Smith, Alex Lieberman-Cribbin, Gabriel De Avila, Sneha Purvey, Hitomi Hosoya, Lekha Mikkilineni, Laura B Oswald, Gurbakhash Kaur, Oren Pasvolsky, Mahmoud Gaballa, Megan M Herr, Peter Forsberg, Murali Janakiram, Myo Htut, Sireesha Asoori Maringanti, Nilesh Kalariya, Hamza Hashmi, Ran Reshef, Douglas W Sborov, Omar Nadeem, Faiz Anwer, Jack Khouri, Shahzad Raza, Djordje Atanackovic, Melissa Alsina, Ciara L Freeman, Frederick L Locke, Peter Voorhees, Larry D Anderson, Shambavi Richard, Thomas Martin, Yi Lin, Krina K Patel, Surbhi Sidana","doi":"10.1200/JCO-24-01730","DOIUrl":"10.1200/JCO-24-01730","url":null,"abstract":"<p><strong>Purpose: </strong>Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), two B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable efficacy in relapsed/refractory multiple myeloma (RRMM). We compare safety, efficacy, and survival among patients with RRMM treated with standard-of-care (SOC) ide-cel or cilta-cel.</p><p><strong>Methods: </strong>Data were from a retrospective chart review of patients with RRMM leukapheresed by December 31, 2022, with the intent to receive SOC ide-cel or cilta-cel at 19 institutions. An inverse probability of treatment weighting (IPTW) approach was used to compare outcomes by therapy type.</p><p><strong>Results: </strong>A total of 641 patients were leukapheresed by December 31, 2022, with ide-cel (n = 386) and cilta-cel (n = 255). Five hundred eighty-six patients were infused (n = 350 for ide-cel; n = 236 for cilta-cel) with a median follow-up of 12.6 and 13.0 months for ide-cel and cilta-cel, respectively. After IPTW, patient characteristics were well balanced. Cilta-cel was associated with higher likelihood of grade ≥3 cytokine release syndrome (CRS; odds ratio [OR], 6.80 [95% CI, 2.28 to 20.33]), infections (OR, 2.03 [95% CI, 1.41 to 2.92]), second primary malignancies (OR, 1.77 [95% CI, 0.89 to 3.56]), and delayed neurotoxicity (OR, 20.07 [95% CI, 4.46 to 90.20]). Cilta-cel was also associated with better treatment responses (≥complete response: OR, 2.42 [95% CI, 1.63 to 3.60]), longer progression-free survival (hazard ratio [HR], 0.48 [95% CI, 0.36 to 0.63]), and longer overall survival (HR, 0.67 [95% CI, 0.46 to 0.97]). No associations were observed between therapy type and immune effector cell-associated neurotoxicity syndrome, any CRS, severe cytopenia at days 30 and 90, or nonrelapse mortality. We observed consistent findings when repeating the analyses restricting the ide-cel cohort to patients infused during the same time period as Food and Drug Administration approval for cilta-cel (≥March 2022).</p><p><strong>Conclusion: </strong>Cilta-cel demonstrated superior efficacy and survival, with higher incidence of certain toxicities, compared with ide-cel.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401730"},"PeriodicalIF":42.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449063","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: Glofitamab for the Treatment of Relapsed/Refractory Mantle Cell Lymphoma.","authors":"Tycel Jovelle Phillips","doi":"10.1200/JCO-25-00088","DOIUrl":"https://doi.org/10.1200/JCO-25-00088","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500088"},"PeriodicalIF":42.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416805","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 for the Treatment of Relapsed/Refractory Mantle Cell Lymphoma.","authors":"Yutaka Shimazu, Yayoi Shimazu","doi":"10.1200/JCO-24-02259","DOIUrl":"https://doi.org/10.1200/JCO-24-02259","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402259"},"PeriodicalIF":42.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416803","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":"Safety and Efficacy of Neoadjuvant Durvalumab Plus Gemcitabine/Cisplatin or Carboplatin in Patients With Operable High-Risk Upper Tract Urothelial Carcinoma: The iNDUCT-GETUG V08 Trial.","authors":"Nadine Houédé, Thierry Chevallier, François Audenet, Constance Thibault, Yann Neuzillet, Christine Abraham, Alexandra Masson-Lecomte, Hélène Gauthier, Gwenaëlle Gravis, Géraldine Pignot, Sophie Tartas, Alain Ruffion, Damien Pouessel, Mathieu Roumiguié, Brigitte Laguerre, Karim Bensalah, Evanguelos Xylinas, Loïc Jaffrelot, Stéphane Droupy, Guillaume Luquiens, Morgan Rouprêt","doi":"10.1200/JCO-25-00179","DOIUrl":"10.1200/JCO-25-00179","url":null,"abstract":"<p><strong>Purpose: </strong>After radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), prognosis is poor for high-risk patients. This study evaluated safety and efficacy of neoadjuvant chemotherapy (cisplatin or carboplatin + gemcitabine) in combination with durvalumab in these patients.</p><p><strong>Patients and methods: </strong>This phase II trial (ClinicalTrials.gov identifier: NCT04617756) included patients with nonmetastatic, high-grade UTUC, on the basis of the ureteroscopic biopsy or urine cytology, and/or infiltrative aspect of the renal pelvis/ureteral wall by computed tomography imaging. Before RNU, patients received durvalumab plus gemcitabine/cisplatin (cohort 1) or durvalumab plus gemcitabine/carboplatin (cohort 2) once every 3 weeks for a total of four cycles (cohort choice on the basis of the glomerular filtration rate). The primary objective was the pathologic complete response (ypT0) rate in each cohort.</p><p><strong>Results: </strong>Fifty patients were enrolled between 2021 and 2024 (31 in cohort 1; 19 in cohort 2). Median age was 68 years (range, 38-79), and 59% were men. Forty-five patients received four cycles of treatment, three patients three cycles, and one patient two cycles. Five patients switched to carboplatin during treatment. At surgery (N = 45 patients), rates of pT0 were 13% (4/29) in cohort 1 and 5% (1/19) in cohort 2. Fifty percent (15/29) of patients were pTa/pT1 in cohort 1, and 42% (8/19) in cohort 2. No severe immunotherapy-mediated toxicity was observed. Four patients had chemotherapy-related grade 3 neutropenia, one grade 4; one patient had grade 3 thrombopenia, one grade 4; and four patients had grade 3 anemia.</p><p><strong>Conclusion: </strong>Although our negative study did not meet its primary end point in either cohort, the combination of durvalumab and platin-based chemotherapy, especially cisplatin, showed promising results in terms of downstaging. The safety profile was good and the surgical risk was not increased.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500179"},"PeriodicalIF":42.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414339","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":"Allogeneic CAR T Cell Products Cemacabtagene Ansegedleucel/ALLO-501 in Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Experience From the ALPHA2/ALPHA Clinical Studies.","authors":"Frederick L Locke, Javier L Munoz, Michael T Tees, Lazaros J Lekakis, Sven de Vos, Rajneesh Nath, Don A Stevens, Shahbaz A Malik, Geoffrey P Shouse, Mehdi Hamadani, Olalekan O Oluwole, Miguel-Angel Perales, David B Miklos, Paul W Fisher, Amy Feng, Lynn Navale, John B Le Gall, Sattva S Neelapu","doi":"10.1200/JCO-24-01933","DOIUrl":"https://doi.org/10.1200/JCO-24-01933","url":null,"abstract":"<p><strong>Purpose: </strong>Off-the-shelf, allogeneic CD19 chimeric antigen receptor (CAR) T cell products may improve access to treatment versus autologous ones. We report the phase 1 experience of the allogeneic CD19 CAR T-cell product cemacabtagene ansegedleucel (cema-cel) and its predecessor, ALLO-501, in CD19 CAR T-naive patients with relapsed/refractory large B-cell lymphoma (R/R LBCL).</p><p><strong>Patients and methods: </strong>In the ALPHA2/ALPHA studies, safety and efficacy of allogeneic CD19 CAR T cells were evaluated in CD19 CAR T treatment-naive patients with R/R LBCL. Patients received healthy donor-derived, human leukocyte antigen-unmatched cema-cel/ALLO-501 following a 3-day lymphodepletion regimen of fludarabine (30 mg/m²/day), cyclophosphamide (300 or 500 mg/m²/day), and escalating doses of the anti-CD52 monoclonal antibody, ALLO-647.</p><p><strong>Results: </strong>As of September 26, 2024, 33 CD19 CAR T-naive patients with LBCL (median age, 66 years; median number of prior therapies, 3) received allogeneic CAR T cells. CAR T cell expansion was observed following infusion, with persistence observed up to 4 months. Overall and complete response rates were 58% and 42%, respectively; median duration of response in patients with a complete response was 23.1 months. The most common treatment-emergent adverse events were hematologic toxicities. No cases of graft-versus-host disease, immune effector cell-associated neurotoxicity syndrome, or grade ≥3 cytokine release syndrome were reported.</p><p><strong>Conclusion: </strong>Allogeneic CD19 CAR T cells demonstrated promising overall and durable complete response rates with a manageable safety profile in CD19 CAR T-naive patients with R/R LBCL, supporting additional evaluation of cema-cel in patients with LBCL.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"101200JCO2401933"},"PeriodicalIF":42.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414328","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":"Minimal Residual Disease-Based End Point for Accelerated Assessment of Clinical Trials in Multiple Myeloma: A Pooled Analysis of Individual Patient Data From Multiple Randomized Trials.","authors":"Qian Shi, Bruno Paiva, Levi D Pederson, Natalie Dimier, Ela Talpes, Thomas J Prior, Alberto Orfao, Philippe Moreau, Pieter Sonneveld, Shaji K Kumar, Jesse G Dixon, Reshma Patel, Blake J Bartlett, Jordan Schecter, Phillip McCarthy, Dirk Hose, Anja Seckinger, D'Agostino Mattia, Hartmut Goldschmidt, Stefania Oliva, Roger G Owen, Kenneth C Anderson, Jesús San-Miguel, Brian G M Durie, Nikhil Munshi","doi":"10.1200/JCO-24-02020","DOIUrl":"https://doi.org/10.1200/JCO-24-02020","url":null,"abstract":"<p><strong>Purpose: </strong>Newly approved drugs and combinations treating multiple myeloma (MM) have resulted in substantial improvements in patients' survival. To deliver rapid access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to evaluate the minimal residual disease-negative complete response (MRD-CR) as an intermediate end point for progression-free survival (PFS) and overall survival (OS) in newly diagnosed (ND) transplant-eligible (NDTE) patients, ND transplant-ineligible (NDTinE) patients, and patients with relapsed/refractory (RR) MM.</p><p><strong>Patients and methods: </strong>Individual patient data from 20 randomized multicenter trials were collected. Eleven studies (4,773 patients) with sufficient data were analyzed to evaluate whether 9- or 12-month MRD-CR classified at a 10^-5 threshold could be reasonably likely to predict the clinical benefit of new agents regarding PFS and OS. Global odds ratio (OR) was estimated using the bivariate Plackett Copula model. Supportive evaluation included correlations of the treatment effects on MRD-CR end points and PFS/OS, evaluated by both linear regression (<i>R</i>²_{weighted least squared}) and Copula (<i>R</i>²_Copula) models.</p><p><strong>Results: </strong>The analysis demonstrated that both 9- and 12-month MRD-CR strongly correlated with PFS at patient level in NDTE patients, NDTinE patients, and patients with RRMM. Global ORs ranged from 3.06 to 16.24, all with 95% CIs excluding 1.0. Encouraging trial-level correlations (<i>R</i>², 0.61-0.70) were observed by pooling three populations and were stronger (<i>R</i>², 0.67-0.78) in the ND population. Similar results were observed for OS.</p><p><strong>Conclusion: </strong>Our findings provided the support for use of MRD-CR classified at a 10^-5 threshold at either 9 or 12 months after starting of the treatment, as an intermediate end point to support accelerated approvals, in future trials in NDTE patients, NDTinE patients, and patients with RRMM.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402020"},"PeriodicalIF":42.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408084","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}