Blood and Lymphatic Cancer-Targets and Therapy最新文献

{"title":"An Updated Indirect Comparison of Elranatamab Versus a Real-World External Control Arm in Triple-Class Refractory Multiple Myeloma.","authors":"Luciano J Costa, Thomas W LeBlanc, Hans Tesch, Pieter Sonneveld, Sarasa M A Johnson, Francis Vekeman, Patrick Hlavacek, Aster Meche, Chai Hyun Kim, Paul Cislo, David M Hughes, Guido Nador, Marco DiBonaventura","doi":"10.2147/BLCTT.S516356","DOIUrl":"10.2147/BLCTT.S516356","url":null,"abstract":"<p><strong>Purpose: </strong>Elranatamab is a BCMAxCD3 bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma (RRMM). The registrational Phase 2 MagnetisMM-3 (NCT04649359) trial was single-armed; the aim of this indirect comparison was to contextualize the efficacy of the most recent 28.4-month follow-up data cut from this trial, allowing for more mature data, with real-world data serving as an external control.</p><p><strong>Patients and methods: </strong>We conducted a retrospective cohort study to indirectly compare the efficacy observed in the elranatamab arm of MagnetisMM-3 Cohort A (BCMA-naïve; N=123) from the March 26, 2024 data cut with COTA, a US-based oncology electronic health record database, as an external control. All MM patients with triple-class refractory disease who initiated a new line of therapy (representing real-world physician's choice) between November 2015 and August 2023 in the COTA database were included. MagnetisMM-3 inclusion (eg, ≥18 years, measurable disease within 90 days of the index, Eastern Cooperative Oncology Group [ECOG] ≤ 2) and exclusion criteria (eg, plasma cell leukemia, smoldering MM) were applied to obtain comparable patient populations across sources. The elranatamab cohort was compared with the physician's choice cohort on progression-free survival (PFS), overall survival (OS), and duration of response (DOR) using Cox proportional hazard models implementing inverse probability of treatment weighting to adjust for any remaining imbalances on confounding variables.</p><p><strong>Results: </strong>N=123 patients treated with elranatamab were compared with 577 patients treated with real-world physicians' choice of therapy. Compared with physician's choice, elranatamab significantly improved PFS (HR = 0.38 [0.22, 0.65], p<0.05), OS (HR = 0.58 [0.35, 0.96], p<0.05), and DOR (HR = 0.16 [0.07, 0.34], p<0.05).</p><p><strong>Conclusion: </strong>In this comparison of patients from the MagnetisMM-3 trial and real-world patients who resemble those from the trial, patients treated with elranatamab exhibited significantly better clinical outcomes compared with treatments currently used in real-world clinical practice.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"15 ","pages":"11-20"},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-Cell Engagers In Multiple Myeloma: A Clinical Review.","authors":"Ahmad Al-Jarrad, Samhar Samer Alouch, Yogesh Chawla, Wilson I Gonsalves","doi":"10.2147/BLCTT.S492116","DOIUrl":"10.2147/BLCTT.S492116","url":null,"abstract":"<p><p>T-cell engagers (TCEs) are engineered to bind both the CD3 subunit on T-cells and specific antigens on tumor cells, triggering T-cell activation and tumor cell lysis. TCEs targeting B-cell maturation antigen (BCMA) and G-protein-coupled receptor, class C, group 5, member D (GPRC5D) have demonstrated significant clinical activity in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM). As a monotherapy, TCEs have had overall response rates (ORRs) of over 60%, with deep and durable hematological responses. Common toxicities include cytokine release syndrome (CRS), infections, and on-target off-tumor effects. Ongoing research looks to enhance the efficacy and tolerability of TCEs for the next generation of products to play an even bigger role in treating patients with MM.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"15 ","pages":"1-10"},"PeriodicalIF":3.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Antibody Drug Conjugate, Belantamab-Mafodotin, in the Treatment of Multiple Myeloma: A Comprehensive Review.","authors":"Adrian Alfonso Almodovar Diaz, Samhar Samer Alouch, Yogesh Chawla, Wilson I Gonsalves","doi":"10.2147/BLCTT.S490021","DOIUrl":"10.2147/BLCTT.S490021","url":null,"abstract":"<p><p>Despite recent advancements in treatments, including proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains mostly incurable with patients frequently experiencing disease relapses due to therapy resistance. Hence there is an urgent need for innovative treatments for patients with relapsed and/or refractory MM (RRMM). This review examines Belantamab mafodotin, the first antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA), which has shown efficacy in pre-clinical and clinical settings for RRMM. BCMA, a type III transmembrane glycoprotein critical for B cell functions, is predominantly expressed in malignant plasma cells making it a promising therapeutic target. ADCs, comprising a monoclonal antibody, a cytotoxic payload, and a linker, offer a targeted and potent therapeutic approach to cancer treatment. Belantamab mafodotin integrates an afucosylated monoclonal antibody and monomethyl auristatin F (MMAF) as its cytotoxic agent. It induces apoptosis in MM cells by disrupting microtubule formation and interfering with important signaling pathways. The series of DREAMM (Driving Excellence in Approaches to MM) studies have extensively evaluated Belantamab mafodotin in various clinical settings. This review provides a comprehensive overview of pre-clinical and clinical data supporting Belantamab mafodotin as a future therapeutic option for RRMM.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"14 ","pages":"71-87"},"PeriodicalIF":3.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly Curative Treatment of High-Risk Acute Promyelocytic Leukemia: Induction and Consolidation with ATRA+ATO+anthracyclines and Maintenance with ATRA+RIF.","authors":"Dan Liu, Juan Tong, Erling Chen, Li Wang, Lei Xue, Xuhan Zhang, Na Zhao, Xing Hu, Changcheng Zheng","doi":"10.2147/BLCTT.S473984","DOIUrl":"10.2147/BLCTT.S473984","url":null,"abstract":"<p><strong>Background: </strong>The aim of the study was to evaluate the efficacy and safety of induction and consolidation with all-trans retinoic acid (ATRA) +arsenic trioxide (ATO) +anthracyclines and maintenance with ATRA +Realgar-<i>Indigo naturalis</i> formula (RIF) for high-risk APL.</p><p><strong>Methods: </strong>Twenty-one patients with high-risk APL treated with ATRA+ATO+ anthracyclines for induction and consolidation and ATRA+RIF for maintenance from 2012 to 2021 were analyzed. Endpoints include morphological complete remission (CR) and complete molecular remission (CMR), early death (ED) and relapse, survival and adverse events (AEs).</p><p><strong>Results: </strong>After induction treatment, all 21 patients (100%) achieved morphological CR and 14 people (66.7%) achieved CMR. Five of the 21 patients did not undergo immunological minimal residual disease (MRD) examination after induction; however, 14 of the remaining 16 patients were MRD negative (87.5%). The median time to achieve CR and CMR was 26 days (range: 16-44) and 40 days (range: 22-75), respectively. The cumulative probability of achieving CR and CMR in 45 days was 100% and 76.2% (95% CI: 56.9-91.3%), respectively. All patients achieved CMR and MRD negativity after the three courses of consolidation treatment. The median follow-up was 66 months (25-142), with no central nervous system relapse and bone marrow morphological or molecular relapse until now, and all patients survived with 100% overall survival and 100% event-free survival. Grade 4 adverse events (AEs) were observed in 3 patients (14.3%) during the induction period including arrhythmia (n = 1), pulmonary infection (n = 1) and respiratory failure (n = 1); and the most frequent grade 3 AEs were pulmonary infection, accounting for 62.0% and 28.6%, respectively, during induction and consolidation treatment, followed by neutropenia, accounting for 42.9% and 38.1%, respectively.</p><p><strong>Conclusion: </strong>For newly diagnosed high-risk APL patients, induction and consolidation with ATRA+ATO+anthracyclines and maintenance with ATRA+RIF is a highly curative treatment approach.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"14 ","pages":"63-69"},"PeriodicalIF":3.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Albumin-to-Globulin Ratio Combined with Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor in Multiple Myeloma with Renal Impairment.","authors":"Yingzi Zhang, Xiajuan Yao, Yaoquan Zhang, Zhuyun Chen, Zhongke Qin, Ying Cai, Wenkai Xia, Hong Hu","doi":"10.2147/BLCTT.S468836","DOIUrl":"10.2147/BLCTT.S468836","url":null,"abstract":"<p><strong>Background: </strong>The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI).</p><p><strong>Methods: </strong>From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index).</p><p><strong>Results: </strong>The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI.</p><p><strong>Conclusion: </strong>ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"14 ","pages":"49-62"},"PeriodicalIF":3.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refractory Burkitt Lymphoma: Diagnosis and Interventional Strategies.","authors":"Francesco Malfona, Anna Maria Testi, Sabina Chiaretti, Maria Luisa Moleti","doi":"10.2147/BLCTT.S407804","DOIUrl":"10.2147/BLCTT.S407804","url":null,"abstract":"<p><p>Despite excellent results in frontline therapy, particularly in pediatric age, refractory Burkitt lymphoma still remains a therapeutic challenge, with dismal outcome. The prognosis is very poor, ranging from less than 10% to 30-40%, with longer survival only in transplanted patients. On account of the paucity of data, mostly reporting on small series of patients, with heterogeneous characteristics and salvage treatments, at present it is impossible to draw definitive conclusions on the treatment of choice for this difficult to treat subset of patients. New insights into Burkitt lymphoma/leukemia cell biology have led to the development of new drugs, currently being tested, directed at different specific targets. Herein, we describe the results so far reported in refractory Burkitt lymphoma/leukemia, with standard treatments and hematopoietic stem cell transplant, and we review the new targeted drugs currently under evaluation.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"14 ","pages":"1-15"},"PeriodicalIF":2.8,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10949171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polycythemia Vera: Barriers to and Strategies for Optimal Management.","authors":"Andrea Duminuco, Patrick Harrington, Claire Harrison, Natalia Curto-Garcia","doi":"10.2147/BLCTT.S409443","DOIUrl":"10.2147/BLCTT.S409443","url":null,"abstract":"<p><p>Polycythemia vera (PV) is a subtype of myeloproliferative neoplasms characterized by impaired quality of life and severe complications. Despite the increasingly in-depth knowledge of this condition, it necessitates a multifaceted management approach to mitigate symptoms and prevent thrombotic and hemorrhagic events, ensuring prolonged survival. The therapeutic landscape has been revolutionized in recent years, where venesection and hydroxycarbamide associated with antiplatelet therapy have a central role and are now accompanied by other drugs, such as interferon and Janus kinase inhibitors. Ongoing research and advancements in targeted therapies hold promise for further enhancing the therapeutic choice for PV management.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"13 ","pages":"77-90"},"PeriodicalIF":2.8,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139038007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zanubrutinib in Mantle Cell Lymphoma Management: A Comprehensive Review.","authors":"Nada Alsuhebany, Congshan Pan, Eileen Holovac, Brian Do, Ali McBride","doi":"10.2147/BLCTT.S426588","DOIUrl":"10.2147/BLCTT.S426588","url":null,"abstract":"<p><strong>Purpose: </strong>The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of zanbrutinib are described.</p><p><strong>Summary: </strong>Mantle cell lymphoma (MCL) is a mature B-cell lymphoma that is typically associated with unfavorable outcomes, and virtually all patients with MCL have refractory or relapsed disease despite aggressive treatment. The treatment paradigm for MCL has transformed dramatically over the past decade owing to rapid advancements in immunotherapy and molecular-targeted therapies. Zanubrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKI) designated for mature B-cell non-Hodgkin's lymphoma (NHL), has drastically improved the survival outcomes in relapsed/refractory (R/R) MCL patients. This selective BTKI is a small molecule that functions by forming a covalent bond in the active site of BTK. The inhibition of BTK activity is essential for the signaling of B-cell antigen receptor (BCR) and cytokine receptor pathways. In a preclinical study, zanubrutinib inhibited malignant B-cell proliferation and reduced tumor growth. Zanubrutinib was granted FDA-accelerated approval based on the results of Phase I and II trials. The investigator-assessed overall response rate was 83.7%, of which 78% of patients achieved complete response. The median duration of response was 19.5 months, and the median progression-free survival was 22.1 months. The most common (≥20%) all-grade adverse events were low neutrophil count (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), low white blood cell count (33.7%), and low platelet count (32.6%).</p><p><strong>Conclusion: </strong>Zanubrutinib is a selective, next-generation, orally active, irreversible BTK inhibitor. The selectivity of zanubrutinib and its superior efficacy, with a well-tolerated safety profile, have proven to be attractive options for other malignancies.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"13 ","pages":"67-76"},"PeriodicalIF":2.8,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"⁹⁰Yttrium Ibritumomab Tiuxetan (Zevalin) for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Report of 5 Cases.","authors":"Jing Wang,&nbsp;Firas Baidoun,&nbsp;Han W Tun,&nbsp;Muhamad Alhaj Moustafa","doi":"10.2147/BLCTT.S398809","DOIUrl":"10.2147/BLCTT.S398809","url":null,"abstract":"<p><p>Radioimmunotherapy (RIT) with radio-labeled monoclonal antibodies to CD20 produces a high response rate in patients with low-grade B-cell lymphomas. The use of this modality in patients with chronic lymphocytic leukemia (CLL) has been sporadic in clinical trials and was hampered by the extensive marrow involvement seen commonly in patients with CLL, which would produce a high risk for marrow aplasia after treatment with RIT. Herein, we report our experience with RIT in 5 patients with CLL or SLL showing short-lived responses and significant myelosuppression. After 90Y-ibritumomab tiuxetan treatment, the median time to relapse was 65 days, and no cases of MDS or AML were observed during follow-up. All patients experienced grade ≥3 thrombocytopenia and neutropenia, with median durations of 39.5 days and 107 days, respectively.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"13 ","pages":"59-65"},"PeriodicalIF":2.8,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/15/c4/blctt-13-59.PMC10559791.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article.","authors":"Munawwar Hussain,&nbsp;Sarvari Yellapragada,&nbsp;Samer Al Hadidi","doi":"10.2147/BLCTT.S272703","DOIUrl":"https://doi.org/10.2147/BLCTT.S272703","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a hematologic malignancy characterized by the abnormal clonal proliferation of plasma cells that may result in focal bone lesions, renal failure, anemia, and/or hypercalcemia. Recently, the diagnosis and treatment of MM have evolved due to a better understanding of disease pathophysiology, improved risk stratification, and new treatments. The incorporation of new drugs, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and high-dose chemotherapy followed by hematopoietic stem cell transplantation, has resulted in a significant improvement in patient outcomes and QoL. In this review, we summarize differential diagnoses and therapeutic advances in MM.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"13 ","pages":"33-57"},"PeriodicalIF":2.8,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/62/blctt-13-33.PMC10508231.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41159979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}