Maria Livia Del Giudice, Sara Galimberti, Gabriele Buda
{"title":"Novel monoclonal antibodies: A really specific therapy for light chain amyloidosis","authors":"Maria Livia Del Giudice, Sara Galimberti, Gabriele Buda","doi":"10.1002/hon.3270","DOIUrl":"https://doi.org/10.1002/hon.3270","url":null,"abstract":"<p>Light chain amyloidosis is a rare disease caused by clonal plasma cells in the bone marrow generating an excessive amount of immunoglobulin light chains. These chains misfold and produce insoluble fibrils that deposit in various organs, including the heart, kidneys, liver, nervous system, and digestive tract. Life expectancy and symptoms during the course of the disease vary depending on which and how many organs are affected. Targeted plasma cell therapy has significantly advanced the clinical management of amyloidosis, with ongoing progress. However, current clinical studies are investigating innovative targets, drug combinations and treatment strategies to improve therapeutic outcomes by minimizing adverse effects and refining patient prognosis in these challenging hematological conditions. In this paper, we review the state of the art regarding the use of anti-amyloid antibodies, as a revolutionary and innovative approach in the current scenario of amyloid treatment.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537830","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 RAS-signaling-pathway-mutation-related prognosis in B-cell acute lymphoblastic leukemia: A report from South China children's leukemia group","authors":"Xinyu Li, Shaofen Lin, Ning Liao, Huirong Mai, Xingjiang Long, Lili Liu, Beiyan Wu, Qiwen Chen, Qian Kong, Xianling Kong, Lixia Liu, Jiayue Qin, Jianpei Fang, Dunhua Zhou","doi":"10.1002/hon.3265","DOIUrl":"https://doi.org/10.1002/hon.3265","url":null,"abstract":"<p>The next-generation sequencing technologies application discovers novel genetic alterations frequently in pediatric acute lymphoblastic leukemia (ALL). RAS signaling pathway mutations at the time of relapse ALL frequently appear as small subclones at the time of onset, which are considered as the drivers in ALL relapse. Whether subclones alterations in the RAS signaling pathway should be considered for risk group stratification of ALL treatment is not decided yet. In this work, we investigate the <i>RAS</i> signaling pathway mutation spectrum and the related prognosis in pediatric ALL. We employed an NGS panel comprising 220 genes. NGS results were collected from 202 pediatric ALL patients. 155 patients (76.7%) harbored at least one mutation. The incidences of <i>RAS</i> signaling pathway mutations are different significantly between T-ALL and B-ALL. In B-ALL, the <i>RAS</i> pathway is mostly involved, and <i>NRAS</i> (17.6%), <i>KRAS</i> (22.7%), and <i>PTPN11</i> (7.7%) were the three most frequently mutated genes. Co-occurring mutations of <i>CREBBP</i> and <i>NRAS</i>, <i>FLT3</i>, or <i>PTPN11</i> (<i>p</i> = 0.002, <i>p</i> = 0.009, and <i>p</i> = 0.003, respectively) were found in this cohort. The 3-year RFS rates for the <i>RAS</i> signaling pathway mutation-positive and negative cases was 76.5 % versus 89.7 % (<i>p</i> = 0.012). Four cases relapsed in the lately 3 years were <i>RAS</i> signaling pathway mutation-positive. <i>RAS</i> signaling pathway mutation is an important biomarker for poorer relapse-free survival in pediatric B-ALL patients despite good early MRD levels.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343061","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":"Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia","authors":"Yuan Sun, Xu Wang, Wen-Min Chen, Yue Hao, Ling-Di Li, Jin-Ying Li, Kai Sun, Zong-Yan Shi, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Ya-Zhen Qin","doi":"10.1002/hon.3264","DOIUrl":"10.1002/hon.3264","url":null,"abstract":"<p>In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KIT<sup>mut</sup>) DNA level is reportedly predictive of relapse in <i>t</i> (8; 21) acute myeloid leukemia (AML). However, the usefulness of KIT<sup>mut</sup> transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 <i>t</i> (8; 21) AML patients with KIT<sup>mut</sup> (D816V/H/Y or N822K) were tested for KIT<sup>mut</sup> transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KIT<sup>mut</sup> were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KIT<sup>mut</sup>-high (KIT_H) group and the KIT<sup>mut</sup>-low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (<i>p</i> = 0.0040 and 0.021, respectively) and Course 2 consolidation (<i>p</i> = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KIT<sup>mut</sup> and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in <i>t</i> (8; 21) AML patient with KIT mutation.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068334","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}
Elisabetta M. Abenavoli, Flavia Linguanti, Matilde Anichini, Vittorio Miele, Francesco Mungai, Marianna Palazzo, Luca Nassi, Benedetta Puccini, Ilaria Romano, Benedetta Sordi, Roberto Sciagrà, Gabriele Simontacchi, Alessandro M. Vannucchi, Valentina Berti
{"title":"Texture analysis of 18F-FDG PET/CT and CECT: Prediction of refractoriness of Hodgkin lymphoma with mediastinal bulk involvement","authors":"Elisabetta M. Abenavoli, Flavia Linguanti, Matilde Anichini, Vittorio Miele, Francesco Mungai, Marianna Palazzo, Luca Nassi, Benedetta Puccini, Ilaria Romano, Benedetta Sordi, Roberto Sciagrà, Gabriele Simontacchi, Alessandro M. Vannucchi, Valentina Berti","doi":"10.1002/hon.3261","DOIUrl":"10.1002/hon.3261","url":null,"abstract":"<p>To recognize patients at high risk of refractory disease, the identification of novel prognostic parameters improving stratification of newly diagnosed Hodgkin Lymphoma (HL) is still needed. This study investigates the potential value of metabolic and texture features, extracted from baseline 18F-FDG Positron Emission Tomography/Computed Tomography (PET) and Contrast-Enhanced Computed Tomography scan (CECT), together with clinical data, in predicting first-line therapy refractoriness (R) of classical HL (cHL) with mediastinal bulk involvement. We reviewed 69 cHL patients who underwent staging PET and CECT. Lesion segmentation and texture parameter extraction were performed using the freeware software LIFEx 6.3. The prognostic significance of clinical and imaging features was evaluated in relation to the development of refractory disease. Receiver operating characteristic curve, Cox proportional hazard regression and Kaplan-Meier analyses were performed to examine the potential independent predictors and to evaluate their prognostic value. Among clinical characteristics, only stage according to the German Hodgkin Group (GHSG) classification system significantly differed between R and not-R. Among CECT variables, only parameters derived from second order matrices (gray-level co-occurrence matrix (GLCM) and gray-level run length matrix (GLRLM) demonstrated significant prognostic power. Among PET variables, SUVmean, several variables derived from first (histograms, shape), and second order analyses (GLCM, GLRLM, NGLDM) exhibited significant predictive power. Such variables obtained accuracies greater than 70% at receiver operating characteristic analysis and their PFS curves resulted statistically significant in predicting refractoriness. At multivariate analysis, only HISTO_EntropyPET extracted from PET (HISTO_Entropy<sub>PET</sub>) and GHSG stage resulted as significant independent predictors. Their combination identified 4 patient groups with significantly different PFS curves, with worst prognosis in patients with higher HISTO_Entropy<sub>PET</sub> values, regardless of the stage. Imaging radiomics may provide a reference for prognostic evaluation of patients with mediastinal bulky cHL. The best prognostic value in the prediction of R versus not-R disease was reached by combining HISTO_Entropy<sub>PET</sub> with GHSG stage.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059170","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}
Maria Anele Romeo, Chiara Focaccetti, Andrea Arena, Rossella Benedetti, Michele Di Crosta, Camilla Palumbo, Maria Saveria Gilardini Montani, Roberta Santarelli, Roberta Gonnella, Gabriella D’Orazi, Roberto Bei, Mara Cirone
{"title":"New insights into the Bortezomib-induced cytotoxic and resistance mechanisms in a primary effusion lymphoma mouse model","authors":"Maria Anele Romeo, Chiara Focaccetti, Andrea Arena, Rossella Benedetti, Michele Di Crosta, Camilla Palumbo, Maria Saveria Gilardini Montani, Roberta Santarelli, Roberta Gonnella, Gabriella D’Orazi, Roberto Bei, Mara Cirone","doi":"10.1002/hon.3262","DOIUrl":"10.1002/hon.3262","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049205","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}
Domenico Albano, Anna Calabrò, Francesco Dondi, Samuele Bagnasco, Alessandra Tucci, Francesco Bertagna
{"title":"The role of baseline 2-[18F]-FDG-PET/CT metrics and radiomics features in predicting primary gastric lymphoma diagnosis","authors":"Domenico Albano, Anna Calabrò, Francesco Dondi, Samuele Bagnasco, Alessandra Tucci, Francesco Bertagna","doi":"10.1002/hon.3266","DOIUrl":"10.1002/hon.3266","url":null,"abstract":"<p>Diffuse Large B-Cell Lymphomas (DLCBL) and mucosa-associated lymphoid tissue (MALT) are the two most common primary gastric lymphomas (PGLs), but have strongly different features. DLBCL is more aggressive, is frequently diagnosed at an advanced stage and has a poorer prognosis. The aim of this retrospective study was to explore the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[<sup>18</sup>F]-FDG-PET/CT) and radiomics features (RFs) in predicting the final diagnosis of patients with PGLs. Ninety-one patients with newly diagnosed PGLs who underwent pre-treatment 2-[<sup>18</sup>F]-FDG-PET/CT were included. PET images were qualitatively and semi-quantitatively analyzed by deriving maximum standardized uptake value body weight (SUVbw), maximum standardized uptake value lean body mass (SUVlbm), maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (gMTV) and total lesion glycolysis of gastric lesion (gTLG), total MTV (tMTV), TLG, and first-order RFs (histogram-related and shape related). Receiver-operating characteristic (ROC) curve analyses were performed to determine the differential diagnostic values of PET parameters. The final diagnosis was DLBCL in 54 (59%) cases and MALT in 37 cases (41%). PGLs showed FDG avidity in 83 cases (90%), 54/54 of DLBCL and 29/37 of MALT. All PET/CT metabolic features, such as stage of disease and tumor size, were significantly higher in DLBCL than MALT; while the presence of <i>H. Pylori</i> infection was more common in MALT. At univariate analysis, all PET/CT metrics were significantly higher in DLBCL than MALT lymphomas, while among RFs only Shape volume_vx and Shape sphericity showed a significant difference between the two groups. In conclusion we demonstrated that 2-[<sup>18</sup>F]-FDG-PET/CT parameters can potentially discriminate between DLBCL and MALT lymphomas with high accuracy. Among first-order RFs, only Shape volume_vx and Shape sphericity helped in the differential diagnosis.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039135","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}
Enrico Grande, Francesco Grippo, Claudio Barbiellini Amidei, Ugo Fedeli, Alberto Tosetto
{"title":"Mortality associated to hematological malignancies across pandemic waves in 2020: A nationwide analysis of multiple causes of death in Italy","authors":"Enrico Grande, Francesco Grippo, Claudio Barbiellini Amidei, Ugo Fedeli, Alberto Tosetto","doi":"10.1002/hon.3263","DOIUrl":"10.1002/hon.3263","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996048","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}
João L. Pereira, Francisca Ferreira, Nuno R. dos Santos
{"title":"Antibody targeting of surface P-selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition","authors":"João L. Pereira, Francisca Ferreira, Nuno R. dos Santos","doi":"10.1002/hon.3257","DOIUrl":"10.1002/hon.3257","url":null,"abstract":"<p>Lymphomas are a heterogeneous group of diseases that originate from T, B or natural killer cells. Lymphoma treatment is based on chemotherapy, radiotherapy, and monoclonal antibody (mAb) or other immunotherapies. The P-selectin glycoprotein ligand 1 (PSGL-1) is expressed at the surface of hematological malignant cells and has been shown to have a pro-oncogenic role in multiple myeloma and lymphoma. Here, we investigated the expression and therapeutic potential of PSGL-1 in T and B cell lymphomas. By flow cytometry analysis, we found that PSGL-1 was expressed in both T and B cell-derived lymphoma cell lines but generally at higher levels in T cell lymphoma cell lines. For most T and B cell-derived lymphoma cell lines, in vitro targeting with the PL1 mAb, which recognizes the PSGL-1 N-terminal extracellular region and blocks functional interactions with selectins, resulted in reduced cell viability. The PL1 mAb pro-apoptotic activity was shown to be dose-dependent, to be linked to increased ERK kinase phosphorylation, and to be dependent on the MAP kinase signaling pathway. Importantly, anti-PSGL-1 treatment of mice xenografted with the HUT-78 cutaneous T-cell lymphoma cell line resulted in decreased tumor growth, had no effect on in vivo proliferation, but increased the levels of apoptosis in tumors. Anti-PSGL-1 treatment of mice xenografted with a Burkitt lymphoma cell line that was resistant to anti-PSGL-1 treatment in vitro, had no impact on tumorigenesis. These findings show that PSGL-1 antibody targeting triggers lymphoma cell apoptosis and substantiates PSGL-1 as a potential target for lymphoma therapy.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982808","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}
Rong Wang, Yi Zhang, Jie Chang, Huafeng Wang, Yinjun Lou, Min Yang, Gaixiang Xu, Hongyan Tong, Wanzhuo Xie, De Zhou, Juying Wei, Wenyuan Mai, Xiujin Ye, Haitao Meng, Jie Jin, Hong-Hu Zhu
{"title":"Venetoclax plus daunorubicin and cytarabine in newly diagnosed acute myeloid leukemia patients: A propensity score-matched analysis","authors":"Rong Wang, Yi Zhang, Jie Chang, Huafeng Wang, Yinjun Lou, Min Yang, Gaixiang Xu, Hongyan Tong, Wanzhuo Xie, De Zhou, Juying Wei, Wenyuan Mai, Xiujin Ye, Haitao Meng, Jie Jin, Hong-Hu Zhu","doi":"10.1002/hon.3260","DOIUrl":"10.1002/hon.3260","url":null,"abstract":"<p>Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy (DAV) has shown safety and efficacy in eligible patients with newly diagnosed acute myeloid leukemia (AML). However, there are no direct comparisons between DAV and 3 + 7 daunorubicin and cytarabine chemotherapy (DA) alone. We performed a propensity score-matched analysis to compare the outcomes of DAV group with historical DA group and identify the clinical and molecular characteristics of patients who might benefit from the DAV regimen. The DAV group had a higher Complete remission (CR) rate than the DA group (90% vs. 55%, <i>p</i> = 0.008). 25 (96%) patients in the DAV group had a higher MRD-negative CRc rate compared with 13 (62%) patients in the DA group (<i>p</i> = 0.006). After a median follow-up duration of 19.15 (IQR 17.13–21.67) months, the DAV group had an improved overall survival (<i>p</i> = 0.001) and event-free survival (<i>p</i> = 0.069), but not disease-free survival (<i>p</i> = 0.136). Collectively, DAV regimen induced high CR rates and deep MRD-negative CRc rates after one cycle of induction therapy, as well as prolonged the overall survival, in young adult patients with AML who were eligible for intensive chemotherapy. The addition of venetoclax to intensive chemotherapy should be considered in the future to achieve better survival advantages in eligible AML patients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982809","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}
Thierry Facon, Philippe Moreau, Ivan Špicka, Kenshi Suzuki, Kwee Yong, Joseph Mikhael, Taro Fukao, Kamlesh Bisht, Nicole M. Armstrong, Sandrine Macé, Marie-Laure Risse, Thomas Martin
{"title":"Isatuximab in combination with carfilzomib and dexamethasone in 1q21+ patients with relapsed/refractory multiple myeloma: Long-term outcomes in the Phase 3 IKEMA study","authors":"Thierry Facon, Philippe Moreau, Ivan Špicka, Kenshi Suzuki, Kwee Yong, Joseph Mikhael, Taro Fukao, Kamlesh Bisht, Nicole M. Armstrong, Sandrine Macé, Marie-Laure Risse, Thomas Martin","doi":"10.1002/hon.3258","DOIUrl":"10.1002/hon.3258","url":null,"abstract":"<p>Gain/amplification of 1q21 (≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma, can negatively affect prognosis, due to its involvement in resistance to anti-myeloma therapy and disease progression. In this updated subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285) in relapsed/refractory multiple myeloma (RRMM), we evaluated progression-free survival (PFS) and depth of response with the anti-CD38 antibody isatuximab plus carfilzomib-dexamethasone (Isa-Kd) versus Kd, in 1q21+ patients and related subgroups, at long-term follow-up (44.2 months). Our analysis included patients with 1q21+ (≥3 copies, with/without high-risk chromosomal abnormality [HRCA]), isolated 1q21+ (≥3 copies, without HRCA), gain(1q21) (3 copies, with/without HRCA), and amp(1q21) (≥4 copies, with/without HRCA). PFS benefit was achieved with Isa-Kd versus Kd in patients with 1q21+ (HR 0.58, 95% CI: 0.37–0.92), with isolated 1q21+ (HR 0.49, 95% CI: 0.27–0.92), with gain(1q21), or amp(1q21), consistent with the overall population and prior interim 1q21+ subgroup analyses. Median PFS with Isa-Kd versus Kd was 25.8 versus 16.2 months in 1q21+ patients and 38.2 versus 16.2 months in patients with isolated 1q21+. Clinically meaningful, higher rates of very good partial response or better, complete response or better (≥CR), minimal residual disease (MRD) negativity, and MRD negativity and ≥CR were reached with Isa-Kd versus Kd in patients with 1q21+, isolated 1q21+, gain(1q21), or amp(1q21). In Isa-Kd and Kd, the MRD negativity and ≥CR rate was 29.3% versus 15.4% in 1q21+ patients, 36.2% versus 12.9% in patients with isolated 1q21+, 27.9% versus 13.5% in patients with gain(1q21), and 31.3% versus 20.0% in patients with amp(1q21), respectively. In conclusion, addition of Isa to Kd in triplet combination therapy has shown PFS benefit and deeper responses, compared with Kd, in 1q21+ patients at higher risk of progression, including patients with isolated 1q21+, gain(1q21), and amp(1q21), thus supporting Isa-Kd an effective treatment option for patients with RRMM.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"42 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944077","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}