EJHaem最新文献

{"title":"Longitudinal assessment of cerebral infarcts and small vessel disease using magnetic resonance imaging in antiphospholipid syndrome: A single-centre retrospective study","authors":"Yishi Tan,&nbsp;Andrew J. Doyle,&nbsp;Jayant Kumar,&nbsp;Peter Somerville,&nbsp;Uzma Faruqi,&nbsp;Anicee Danaee,&nbsp;Pu-Lin Luo,&nbsp;Beverley J. Hunt,&nbsp;Karen A. Breen","doi":"10.1002/jha2.1065","DOIUrl":"https://doi.org/10.1002/jha2.1065","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Stroke is the most frequent arterial thrombosis in antiphospholipid syndrome (APS) with high rates of recurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and patients</h3>\u0000 \u0000 <p>A retrospective, single-centre 10-year review of patients with APS having sequential cerebral magnetic resonance imaging (MRI) was performed to describe ischaemic features in APS and associated disease risk factors and progression over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 120 patients and 307 scans were included with 67% of patients receiving vitamin K antagonists (VKA). Note that 65% of patients had baseline ischaemic features with white matter hyperintensities (WMH), as a feature of small vessel disease (SVD), seen in 79% of abnormal scans. Fifteen percent of patients had progressive ischaemic changes with 83% demonstrating progressive WMH and 33% new infarcts (predominantly lacunar) on sequential scans. Progression-free survival for progressive ischaemia was 88% at 5 years. Multivariate analysis showed longer follow-up was a risk for developing progressive ischaemia (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.13–1.86, <i>p</i> = 0.005). Hypertension (56% vs. 30%, <i>p</i> = 0.04) and ischaemic heart disease (22% vs. 6%, <i>p</i> = 0.04) were more prevalent with progressive ischaemia. There was no difference in progression or bleeding events according to VKA therapeutic intensity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>These results show SVD is a common feature of APS using MRI with progressive changes despite anticoagulation. Traditional risk factors for cerebrovascular disease were associated with progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362752","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 prognostic value of POD24 in relapsed/refractory follicular lymphoma—A SCHOLAR-5 analysis","authors":"Eve H. Limbrick-Oldfield,&nbsp;Steve Kanters,&nbsp;Markqayne D. Ray,&nbsp;Timothy Best,&nbsp;Madhu Palivela,&nbsp;Sara Beygi,&nbsp;Anik R. Patel,&nbsp;John G. Gribben,&nbsp;Paola Ghione","doi":"10.1002/jha2.1104","DOIUrl":"https://doi.org/10.1002/jha2.1104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Follicular lymphoma (FL) has a heterogeneous prognosis. Progression within 24 months of starting front-line therapy (POD24) is prognostic of overall survival (OS). Despite its prognostic value in early lines, the role of POD24 in relapsed/refractory (R/R) patients initiating later lines of therapy (LoTs) is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed the SCHOLAR-5 real-world cohort to investigate whether POD24 is prognostic in patients with R/R FL initiating ≥3rd LoT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 128 SCHOLAR-5 patients, 34 patients experienced POD24. POD24 patients received their ≥3 LoT after a shorter time compared with non-POD24 patients (median 42.0 months [range: 8.8‒17.8] vs. 109.9 months [range: 29.6‒310.2]). Using a time-dependent multivariate Cox model, POD24 was predictive of shorter OS from initiation of ≥3rd LoT with a hazard ratio (HR) of 2.44 (95% confidence interval [CI]: 1.20‒4.96). For progression-free survival, using a multivariate repeated-measures Cox model, the effect was similar but not statistically significant (HR: 1.45; 95% CI: 0.94‒2.11).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that among patients with R/R FL initiating a ≥3rd LoT, POD24 patients reach these LoTs sooner after diagnosis and POD24 remains prognostic of subsequent OS. This suggests that POD24 status can inform clinical decision making in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362674","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":"Elimination of residual adult T-cell leukaemia clones by Tax-targeted dendritic cell vaccine","authors":"Tadafumi Iino,&nbsp;Atsuhiko Hasegawa,&nbsp;Takaji Matsutani,&nbsp;Koichi Akashi,&nbsp;Mari Kannagi,&nbsp;Youko Suehiro","doi":"10.1002/jha2.1072","DOIUrl":"https://doi.org/10.1002/jha2.1072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A pilot clinical study of a Tax peptide-pulsed dendritic cell (DC) vaccine for adult T-cell leukaemia/lymphoma (ATL) indicated favourable clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated its anti-tumour effect by T cell receptor (TCR) repertoire analysis in samples from an enrolled ATL patient who achieved a 10-year complete remission after DC vaccination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this patient, the dominant residual ATL clones that had persisted following previous treatment entirely disappeared within 3 years after DC vaccination. Additionally, the DC vaccine restored TCR repertoire diversity of normal T cells and newly induced functional Tax-specific CD8⁺ T cell clones.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The recovery of normal T cell immunity mediated by the DC vaccine may contribute to this long-lasting remission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362753","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":"Real-World Data on Lymphoma in Adolescents and Young Adults (AYA)—Report From the Lymphoma and Related Diseases Registry (LaRDR)","authors":"Evangeline Y. Wong,&nbsp;Cameron Wellard,&nbsp;Jun Yen Ng,&nbsp;Eliza Chung,&nbsp;Zoe K. McQuilten,&nbsp;Stephen Opat,&nbsp;Erica M. Wood,&nbsp;Dipti Talaulikar","doi":"10.1002/jha2.1096","DOIUrl":"10.1002/jha2.1096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Lymphoma is a common malignancy among adolescents and young adults (AYAs) which is generally defined as 15–39 years. Relative to other age groups, lymphoma in AYAs remains understudied with heterogeneous treatment options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a retrospective review of patients aged 18–60 years in the Australasian Lymphoma and Related Diseases Registry (LaRDR) with new diagnoses of the common subtypes of lymphoma in AYAs between January 2016 and April 2023. The subtypes are classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and Burkitt lymphoma (BL). Patient demographics, disease characteristics, treatment and outcome data were collected, and comparisons were made between AYAs (18–39 years) and older adults (OAs) (aged 40–60).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AYAs had higher rates of cHL and PMBCL whereas OAs presented more frequently with DLBCL. AYAs with cHL and PMBCL had higher rates of early-stage and low-risk disease than OAs. In contrast, both AYAs and OAs were more likely to present with advanced-stage DLBCL and BL. AYAs with cHL were more likely to be treated with BEACOPP as compared to OAs who were more commonly treated with ABVD. There was no significant difference in treatment regimens for DLBCL, PMBCL or BL between AYAs and OAs. AYAs with cHL had better overall survival (OS) compared to OAs; specifically, cHL AYAs had better OS and DLBCL AYAs had better progression-free survival (PFS) and OS compared to OAs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study provides valuable data on patient and disease characteristics, treatments used and outcomes in AYA compared to OA aged 40–60 years. Registry data such as from LaRDR can help improve treatment standardisation and AYA patient outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed clinical trial registration is not needed for this submission</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070036","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":"Relapsed Philadelphia chromosome-positive B-cell acute lymphoblastic leukaemia responds well to a combination of modified hyper-CVAD, blinatumomab and tyrosine kinase inhibitor","authors":"Gaétan Basile,&nbsp;Jean Galtier,&nbsp;Titouan Cazaubiel,&nbsp;Edouard Forcade,&nbsp;Emilie Klein,&nbsp;Audrey Bidet,&nbsp;Carmen Botella-Garcia,&nbsp;Clémence Mediavilla,&nbsp;Laurence Clement,&nbsp;Pierre-Yves Dumas,&nbsp;Arnaud Pigneux,&nbsp;Thibaut Leguay","doi":"10.1002/jha2.1064","DOIUrl":"10.1002/jha2.1064","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Adults with relapsed or refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia (R/R Ph+ BCP-ALL) have a dismal outcome. Blinatumomab as a single agent has shown activity in R/R Ph- BCP-ALL, and second or third-generation tyrosine kinase inhibitors (TKIs) can produce high remission rates in Ph+ leukaemias. We aimed to assess the activity of blinatumomab and TKI in combination with intensive chemotherapy in the relapsed or refractory setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ten patients with R/R Ph+ BCP-ALL were treated with the combination of a modified hyper-CVAD (mHCVAD) regimen (cyclophosphamide, vincristine, adriamycin, dexamethasone), blinatumomab and TKI (mainly ponatinib).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Complete remission (CR) was achieved in 10/10 patients, with deep molecular responses, and 6/10 were alive in remission after a median follow-up of 19.4 months. Three major cardiovascular events were noted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These preliminary data, suggest that the mHCVAD-blinatumomab-TKI (mainly ponatinib) regimen may achieve a high rate of CR with undetectable measurable residual disease in adults with R/R Ph+ BCP-ALL and could be proposed to such patients, but cardiovascular or infectious complications should be warning, especially in older or frail patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061505","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":"Angioimmunoblastic T-cell lymphoma: Characterization of clonal T and B cells and a patient-derived xenograft study of coexisting T- and B-cell proliferation","authors":"Xiaoxian Zhao,&nbsp;Deepa Jagadeesh,&nbsp;Juraj Bodo,&nbsp;Lisa Durkin,&nbsp;Daniel J. Lindner,&nbsp;Sarah L. Ondrejka,&nbsp;Eric D. Hsi","doi":"10.1002/jha2.1080","DOIUrl":"10.1002/jha2.1080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive lymphoma with a poor prognosis. AITL is associated with Epstein–Barr virus (EBV)-positive B cells in most cases, suggesting a possible role for the virus in the pathobiology of AITL. Cell lines from AITL patients do not exist and models of human AITL are needed. We aim to establish such a model and use it for preclinical therapeutic evaluation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Primary lymph node tissue from an AITL patient was used for tumor cell isolation and injection to NSG mice. The established patient-derived xenograft (PDX) model was characterized by immunophenotyping, whole-exome sequencing (WES), and T/B-cell receptor gene rearrangement studies. In vivo AITL PDX trials were performed with elotuzumab, romidepsin, and rituximab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An AITL PDX mouse model that includes a coexisting EBV+ B-cell proliferation was established. We confirmed clonal identity of the engrafted T cells with the primary T-lymphoma cells. WES on DNA from xenografted sorted T and B cells identified eight and three mutations previously reported in the COSMIC database, respectively. Primary tumor cells could be passaged serially in NSG mice with an increasing percentage of monoclonal B cells that mimic the human condition in which the clonal B-cell component in some cases may mask an underling T-cell lymphoma. In this PDX mouse study, single agent elotuzumab or rituximab significantly improved mice survival. Survival was further improved when elotuzumab or romidepsin was combined with rituximab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>To our knowledge, this is the first molecular characterization of AITL model coexisting with associated EBV+ B cells, and use of such a PDX model for therapeutic evaluation of agents targeting both malignant T cells and B cells simultaneously.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061575","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":"Chronic Severe Neutropenia Associated With Intravenous Immunoglobulin for Multifocal Motor Neuropathy","authors":"Shannon Ugarte,&nbsp;Talia Gebhard,&nbsp;David R. Cornblath,&nbsp;Steven S. Scherer,&nbsp;Daria V. Babushok","doi":"10.1002/jha2.1102","DOIUrl":"10.1002/jha2.1102","url":null,"abstract":"<p>Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy derived from pooled donor immunoglobulins and used for treatment of various autoimmune conditions. Here we report the diagnosis and management of IVIG-induced chronic severe neutropenia with absolute neutrophil count &lt;0.5×10³/µL in a patient with multifocal motor neuropathy. Serial blood count showed a cyclical pattern of neutropenia: worsening 24–48 h post-IVIG, then gradually improving before the next infusion. IVIG-induced neutropenia is rare, with previous reports of predominantly mild transient neutropenia. Our case describes chronic severe neutropenia that developed years after starting IVIG. We summarize available evidence and management strategies for IVIG-associated neutropenia.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054436","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":"A Complex Presentation of Multiple Myeloma With Renal Complications in a Young Female: Diagnostic Challenges and Treatment Approach","authors":"Hem Prajapati,&nbsp;Yash M. Patel,&nbsp;Ajay C. Parmar,&nbsp;Sahaj Y. Patel,&nbsp;Tasin Mohammedyakub Shaikhjiwala","doi":"10.1002/jha2.1093","DOIUrl":"10.1002/jha2.1093","url":null,"abstract":"<p>A previously healthy 30-year-old woman experienced worsening back pain, fatigue, weakness, loss of appetite, and facial puffiness. After 18 months of these symptoms, she was diagnosed with multiple myeloma, which was also damaging her kidneys. The treatment involved a combination of medications and blood transfusions, leading to improved kidney function. Despite the challenges of managing her condition as a mother of young children, she remains hopeful. This case emphasizes the need for awareness of multiple myeloma in younger patients and the importance of early diagnosis and multidisciplinary care for managing this chronic illness.</p><p><b>Trial Registration</b>: The authors have confirmed clinical trial registration is not needed for this submission</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048771","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":"A novel TERT variant associated with a telomere biology disorder and challenges in variant classification","authors":"Vahid Pazhakh,&nbsp;Lucy C. Fox,&nbsp;Nicole Den Elzen,&nbsp;Matthew R. Emerson,&nbsp;Scott B. Cohen,&nbsp;Tracy M. Bryan,&nbsp;Kevin Norris,&nbsp;Duncan M. Baird,&nbsp;Tara Cochrane,&nbsp;John Mackintosh,&nbsp;Ashleigh Scott,&nbsp;Piers Blombery","doi":"10.1002/jha2.1066","DOIUrl":"10.1002/jha2.1066","url":null,"abstract":"<p>Telomere biology disorders (TBDs) are inherited conditions associated with multisystem manifestations. We describe clinical and functional characterisation of a novel TERT variant. Whole-genome sequencing was performed along with single <i>telomere</i> length analysis (<i>STELA</i>). Telomerase activity and processivity were assessed. A novel TERT variant (K710R) was detected in a patient with classic TBD features showing reduced telomerase activity and processivity. Despite clinical and functional evidence, the variant was classified as a variant of uncertain significance. We have described a novel TERT variant and highlighted the need for further refinement of variant classification specific for TBDs.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048778","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":"Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma—A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone","authors":"Tobias S. Slørdahl,&nbsp;Frida Bugge Askeland,&nbsp;Margrete Sofie Sætre Hanssen,&nbsp;Håkon Hov,&nbsp;Stine Marie Sundt-Hansen,&nbsp;Sofia Lindahl,&nbsp;Nils Tore Vethe,&nbsp;Henrik Hjorth-Hansen,&nbsp;Mona H. Fenstad,&nbsp;Anders Waage,&nbsp;Øyvind Hjertner,&nbsp;Fredrik Schjesvold,&nbsp;Anders Sundan","doi":"10.1002/jha2.1091","DOIUrl":"10.1002/jha2.1091","url":null,"abstract":"<p>Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care. Autophagic protein degradation is currently not targeted in myeloma treatment. This Phase I trial showed that the combination of the proteasome inhibitor carfilzomib and the autophagy inhibitor hydroxychloroquine was well tolerated in patients with relapsed/refractory multiple myeloma. Adverse events were mostly Grades 1 and 2. An overall response rate of 44% indicates a meaningful clinical efficacy of this combination.</p><p><b>Trial Registration</b>: The study was registered at clinicaltrials.gov # NCT04163107.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048748","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}