American Journal of Hematology最新文献

{"title":"The spectrum of sickle cell disease.","authors":"Barbara J Bain","doi":"10.1002/ajh.27494","DOIUrl":"10.1002/ajh.27494","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":"296-297"},"PeriodicalIF":10.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood Plasma Methylated DNA Markers in the Detection of Lymphoma: Discovery, Validation, and Clinical Pilot.","authors":"Thomas E Witzig, William R Taylor, Douglas W Mahoney, William R Bamlet, Patrick H Foote, Kelli N Burger, Karen A Doering, Mary E Devens, Jacquelyn R Arndt, Maria C O'Connell, Calise K Berger, Anne J Novak, James R Cerhan, Jacquelyn Hennek, Slava Katerov, Hatim T Allawi, Dragan Jevremovic, Linda N Dao, Rondell P Graham, John B Kisiel","doi":"10.1002/ajh.27533","DOIUrl":"10.1002/ajh.27533","url":null,"abstract":"<p><p>Lymphoma is one of the leading causes of cancer and cancer deaths and yet has not been amenable to population screening. The role of methylated DNA markers (MDMs) in the detection of lymphoma has not been extensively studied. We aimed to discover, validate, and test tissue-derived MDMs of lymphoma in archival plasma specimens. Reduced representation bisulfite sequencing (RRBS) was performed on a discovery set of frozen tissues. MDMs identified were converted to methylation-specific PCR assays and validated on independent formalin-fixed, paraffin-embedded (FFPE) tissues. Target enrichment long-probe quantitative-amplified signal (TELQAS) assays were developed and assayed in plasma-extracted, bisulfite-converted DNA from independent treatment-naïve lymphoma patients and healthy controls. Prediction of cancer status was modeled using random forest model with in silico cross-validation. After discovery and validation in tissue, 16 TELQAS assays (ZNF503, VWA5B1, HOXA9, GABRG3, ITGA5, MAX.chr17.7190, BNC1, CDK20, MAX.chr4.4069, TPBG, DNAH14, SYT6, CACNG8, FAM110B, ADRA1D, and NRN1) were selected for testing in plasma. These detected 78% (95% CI, 74%-82%) of lymphoma cases at 90% specificity. Excluding marginal zone and T-cell lymphomas, sensitivity increased to 84% (80%-88%). MDMs in plasma show promise to detect lymphoma and are candidates for inclusion in multi-cancer detection studies.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":"218-228"},"PeriodicalIF":10.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oh node: Extranodal nodular involvement of chronic lymphocytic leukemia in the colon.","authors":"Michael Keith Alister Zimmerman, Lindsay Wilde","doi":"10.1002/ajh.27467","DOIUrl":"10.1002/ajh.27467","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":"298-299"},"PeriodicalIF":10.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of mutation type and chromosome fragility in Fanconi anemia.","authors":"María José Ramírez, Roser Pujol, Jordi Minguillón, Massimo Bogliolo, Ilaria Persico, Debora Cavero, Aurora de la Cal, Paula Río, Susana Navarro, José Antonio Casado, Almudena Bailador, Antonio Sanchez de la Fuente, Miguel López de Heredia, Francisco Almazán, M Luisa Antelo, Bienvenida Argilés, Isabel Badell, Marta Baragaño, Cristina Beléndez, Mar Bermúdez, Marta Bernués, María Isabel Buedo, Estela Carrasco, Albert Català, Dolors Costa, Isabel Cuesta, Rafael Fernandez-Delgado, Ana Fernández-Teijeiro, Ángela Figuera, Marta García, Ainhoa Gondra, Macarena González, Soledad González Muñiz, Ines Hernández-Rodríguez, Fátima Ibañez, Nicholas John Kelleher, Francisco Lendínez, Mónica López, Ricardo López-Almaraz, Inmaculada Marchante, Carmen Mendoza, José Nieto, Emilio Ojeda, Salvador Payán-Pernía, Irene Peláez, Inmaculada Pérez de Soto, Raquel Portugal, María A Ramos-Arroyo, Alexandra Regueiro, Ana Rodríguez, Jordi Rosell, Raquel Saez, José Sánchez, Martha Sánchez, MªLeonor Senent, María Tapia, Juan Pablo Trujillo-Quintero, José Manuel Vagace, Jaime Verdú-Amorós, Victória Verdugo, Isabel Vidales, Jasson Villarreal, Cristina Díaz-de-Heredia, Julián Sevilla, Juan Antonio Bueren, Jordi Surrallés","doi":"10.1002/ajh.27520","DOIUrl":"10.1002/ajh.27520","url":null,"abstract":"<p><p>Fanconi anemia (FA) is a rare genetic disease characterized by high phenotypic and genotypic heterogeneity, and extreme chromosome fragility. To better understand the natural history of FA, identify genetic risk and prognostic factors, and develop novel therapeutic strategies, the Spanish Registry of Patients with FA collects data on clinical features, chromosome fragility, genetic subtypes, and DNA sequencing with informed consent of participating individuals. In this article, we describe the clinical evolution of 227 patients followed up for up to 30 years, for whom our data indicate a cumulative cancer incidence of 86% by age 50. We found that patients with lower chromosome fragility had a milder malformation spectrum and better outcomes in terms of later-onset hematologic impairment, less severe bone marrow failure, and lower cancer risk. We also found that outcomes were better for patients with mutations leading to mutant FANCA protein expression (genetic hypomorphism) than for patients lacking this protein. Likewise, prognosis was consistently better for patients with biallelic mutations in FANCD2 (mainly hypomorphic mutations) than for patients with biallelic mutations in FANCA and FANCG, with the lack of the mutant protein in patients with biallelic mutations in FANCG contributing to their poorer outcomes. Our results regarding the clinical impact of chromosome fragility and genetic hypomorphism suggest that mutant FA proteins retain residual activity. This finding should encourage the development of novel therapeutic strategies aimed at partially or fully enhancing mutant FA function, thereby preventing or delaying bone marrow failure and cancer in patients with FA. Clinical Trial Registration number: NCT06490510.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":"272-284"},"PeriodicalIF":10.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Flow Cytometric Antibody Panel and Dedicated Analysis Algorithm for Automated Fully Standardized Minimal Residual Disease Detection in Chronic Lymphocytic Leukemia","authors":"Robby Engelmann, Juan Flores-Montero, Joyce Schilperoord-Vermeulen, Matthias Ritgen, Paul J. Hengeveld, Saskia Kohlscheen, Georgiana Grigore, Rafael Fluxa Rodriguez, Quentin Lecrevisse, Jan Philippé, Neus Villamor, Paula Fernandez, Leire Burgos, Jacques J. M. van Dongen, Alberto Orfao, Anton W. Langerak, Sebastian Böttcher","doi":"10.1002/ajh.27604","DOIUrl":"https://doi.org/10.1002/ajh.27604","url":null,"abstract":"&lt;p&gt;Submicroscopic levels of leukemic cells that persist after treatment are commonly designated as measurable residual disease (MRD). The last decade has witnessed a growing body of evidence proving the prognostic significance of MRD for both progression-free and overall survival in chronic lymphocytic leukemia (CLL) [&lt;span&gt;1, 2&lt;/span&gt;]. Moreover, MRD detection is now increasingly used to tailor treatment in accordance with the needs of the individual patient [&lt;span&gt;3&lt;/span&gt;]. Currently accepted flow cytometry assays reach a detection limit of 10&lt;sup&gt;−4&lt;/sup&gt;, but logically, MRD detection with higher sensitivity (e.g., 10&lt;sup&gt;−5&lt;/sup&gt;) holds promise for further improved prediction.&lt;/p&gt;\u0000&lt;p&gt;The European Research Initiative on CLL (ERIC) has successfully developed a standardized 4-color MRD flow assay featuring a fixed combination of markers, gates, and instructions for the application of gates with a sensitivity of 10&lt;sup&gt;−4&lt;/sup&gt; [&lt;span&gt;4&lt;/span&gt;]. The more recent ERIC 8-color MRD flow tube reportedly achieves a sensitivity of 10&lt;sup&gt;−5&lt;/sup&gt; [&lt;span&gt;5&lt;/span&gt;], but lacks the precise description of an analysis strategy. Therefore, we assessed the reproducibility of the current benchmark ERIC 8-color CLL MRD method (Figure 1A, Figure S1A, Table S1, see also supplemental materials and methods). A total of 99 samples from our dilution experiments were acquired and fully blinded. MRD levels were reported by four recognized experts with long-standing experience in CLL MRD flow (including multicentric international trials performed at national MRD reference laboratories). MRD levels down to an expected MRD level of 10&lt;sup&gt;−4&lt;/sup&gt; were reproducibly and accurately reported by the experts (average agreement to expected: 92%). However, MRD levels between 10&lt;sup&gt;−4&lt;/sup&gt; and 10&lt;sup&gt;−5&lt;/sup&gt; from the dilution series were scored as expected in 74% of all cases only. Importantly, 23% of normal donor samples were considered MRD positive, albeit usually at very low levels (mean reported level: 5.3 × 10&lt;sup&gt;−5&lt;/sup&gt; range: 7.3 × 10&lt;sup&gt;−6&lt;/sup&gt;–1 × 10&lt;sup&gt;−4&lt;/sup&gt;). Furthermore, the data suggested personal biases of individual experts (compare Figure 1A, left and right panels). Despite the described variability, we acknowledge that the accuracy of the ERIC 8-color CLL MRD method at levels below 10&lt;sup&gt;−4&lt;/sup&gt; might be better than reported herein if the individual pre-therapeutic immunophenotype is known. Conversely, we hypothesized that reproducible MRD assessments might be demanding even at levels above 10&lt;sup&gt;−4&lt;/sup&gt; for operators with lesser experience.&lt;/p&gt;\u0000&lt;figure&gt;&lt;picture&gt;\u0000&lt;source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/1cdd94d0-67bd-4377-815f-208888bd3680/ajh27604-fig-0001-m.jpg\"/&gt;&lt;img alt=\"Details are in the caption following the image\" data-lg-src=\"/cms/asset/1cdd94d0-67bd-4377-815f-208888bd3680/ajh27604-fig-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/575305f7-070d-401f-b370-023f2cbef650/ajh27604-fig-0001-m.png\" title=\"Details are in the caption foll","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"31 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031076","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":"NOTCH1 Mutations Are Associated With Therapy-Resistance in Patients With B-Cell Lymphoma Treated With CD20xCD3 Bispecific Antibodies","authors":"Emil R. Kyvsgaard, Morten Grauslund, Lene Sjø, Linea Cecilie Melchior, Trine Lønbo Grantzau, Lise Mette Rahbek Gjerdrum, Trine Trab, Lærke Sloth Andersen, Anne Ortved Gang, Marie Breinholt, Michael Boe Møller, Jacob Haaber Christensen, Thomas Stauffer Larsen, Michael Roost Clausen, Caroline H. Riley, Carsten U. Niemann, Kirsten Grønbæk, Martin Hutchings, Simon Husby","doi":"10.1002/ajh.27601","DOIUrl":"https://doi.org/10.1002/ajh.27601","url":null,"abstract":"&lt;p&gt;CD20 × CD3 bispecific antibodies such as glofitamab, epcoritamab, and mosunetuzumab are novel T cell engaging antibodies which have all shown convincing results and obtained FDA and EMA approval for the treatment of relapsed/refractory diffuse large B cell lymphomas (DLBCL) or follicular lymphoma (FL) with ≥ 2 prior lines of treatment [&lt;span&gt;1&lt;/span&gt;]. However, approximately 50% of patients do not achieve remission when treated with single agent CD20 × CD3 bispecific antibodies.&lt;/p&gt;\u0000&lt;p&gt;Subgroup analysis of pivotal phase I/II trials have identified elevated LDH &gt; 250 U/L, high tumor burden, and refractory disease as risk factors for lack of response to bispecific antibodies for refractory/relapsed DLBCL [&lt;span&gt;1&lt;/span&gt;]. Downregulated TP53 target signatures, upregulated expression of MYC target genes, truncating mutations in &lt;i&gt;MS4A1&lt;/i&gt; (the gene encoding CD20), and loss of CD20 antigen have been identified as predictive factors for lack of response [&lt;span&gt;2-5&lt;/span&gt;]. Previously, tumor mutations in &lt;i&gt;TP53&lt;/i&gt; have been associated with poor response to both immunochemotherapy (i.e. R-CHOP) and CD19 CAR-T cell therapy in patients with B-cell lymphoma, but have not yet been examined thoroughly with long-term follow-up in patients treated with CD20 × CD3 bispecific antibodies.&lt;/p&gt;\u0000&lt;p&gt;In this retrospective study, we included patients from Rigshospitalet, Copenhagen, and Vejle University Hospital, both in Denmark, who received CD20 × CD3 bispecific antibodies between 2017 and 2023 as part of phase 1 or phase 2 clinical trials. The full list of regimens used are shown in Table S1. For exhaustive methods used, refer to the Supporting Information S1.&lt;/p&gt;\u0000&lt;p&gt;We collected pre-treatment formalin-fixed and paraffin-embedded (FFPE) archival specimens from 106 patients, of which 56 had sufficient DNA quantity and tumor involvement for clinical grade diagnostic next-generation sequencing (NGS). NGS was performed with a custom lymphoma panel designed in-house covering 59 commonly mutated genes in lymphoid malignancies.&lt;/p&gt;\u0000&lt;p&gt;We examined pre-treatment tumors from 56 patients with B-cell NHL, who received CD20 × CD3 bispecific antibodies between 2017 and 2023 and had sufficient tissue for NGS sequencing. The median age at first administration of CD20 × CD3 bispecific antibody was 70 years, 60.7% were male, and the median number of prior lines of therapy was three (Table S1). Median follow-up time was 24.2 months. Mutational profiling was additionally performed on 14 paired post-CD20 × CD3 bispecific antibody relapse samples.&lt;/p&gt;\u0000&lt;p&gt;Of all mutations found in pre-CD20 × CD3-treatment biopsies &lt;i&gt;NOTCH1&lt;/i&gt; (detected in 4/56 [7%] of patients, Figure S1), along with &lt;i&gt;BRAF&lt;/i&gt; and &lt;i&gt;EZH2,&lt;/i&gt; had the strongest association with inferior PFS in a univariate Cox model (HR: 3.46, 95% CI 1.16–10.3, &lt;i&gt;p&lt;/i&gt; = 0.026, Tables S2 and S4, Figure S8). Furthermore, pre-CD20 × CD3-treatment &lt;i&gt;NOTCH1&lt;/i&gt; mutated tumors conferred significantly worse outcomes in Kaplan–Mei","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"38 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031075","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":"Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns","authors":"Mizuna Otsuka, Tomohiro Koga, Remi Sumiyoshi, Shoichi Fukui, Yuko Kaneko, Takayuki Shimizu, Atsushi Katsube, Shingo Yano, Yasufumi Masaki, Makoto Ide, Hajime Yoshifuji, Masayasu Kitano, Yasuharu Sato, Naoki Sawa, Hiroaki Niiro, Naoya Nakamura, David C. Fajgenbaum, Frits van Rhee, Atsushi Kawakami","doi":"10.1002/ajh.27612","DOIUrl":"https://doi.org/10.1002/ajh.27612","url":null,"abstract":"Individuals diagnosed with Castleman disease (CD) and TAFRO syndrome (characterized by thrombocytopenia, anasarca, fever, bone marrow fibrosis, and organomegaly) displays a wide range of clinical symptoms, including varying patterns of lymph node enlargement, systemic inflammation, and impaired organ function. Some patients may present with both CD and TAFRO syndrome concurrently. A retrospective study conducted across multiple centers in Japan examined 321 cases to determine if the quantity and position of swollen lymph nodes could forecast the clinical progression and intensity of these conditions. Interestingly, the study revealed that patients with TAFRO syndrome exhibited lymphadenopathy across all ranges of lymph node region counts. Moreover, no specific clinical patterns were associated with the number of affected lymph node regions in CD patients, regardless of whether they also had TAFRO syndrome. These results enhance our understanding of the clinical variability in CD and TAFRO syndrome, suggesting that a comprehensive clinical evaluation, rather than relying solely on lymph node count, is crucial for effectively managing these conditions. Additional studies are required to establish reliable diagnostic markers and to predict disease severity at the time of diagnosis, ultimately improving patient outcomes.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"113 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031074","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":"Combination of Biological Aging and Genetic Susceptibility Helps Identifying At‐Risk Population of Venous Thromboembolism: A Prospective Cohort Study of 394 041 Participants","authors":"Zhensheng Hu, Jiatang Xu, Runnan Shen, Liling Lin, Yangfan Su, Chaoyu Xie, Guochang You, Yi Zhou, Kai Huang","doi":"10.1002/ajh.27605","DOIUrl":"https://doi.org/10.1002/ajh.27605","url":null,"abstract":"Phenotypic age acceleration (PhenoAgeAccel) is a novel clinical aging indicator. This study was carried out to investigate the relationship between PhenoAgeAccel and the incidence of VTE, as well as to integrate PhenoAgeAccel with genetic susceptibility to improve risk stratification of VTE. The study included 394 041 individuals from the UK Biobank. Phenotypic age was calculated based on actual age and clinical biomarkers. PhenoAgeAccel presents the residual obtained from a linear regression of phenotypic age against actual age, reflecting the rate of aging. Significant associations were observed between PhenoAgeAccel and higher risk of VTE (Hazard ratio [HR] 1.37, 95% CI: 1.32–1.42), deep vein thrombosis (DVT, HR 1.35, 95% CI: 1.29–1.42), and PE (pulmonary embolism, HR 1.41, 95% CI: 1.34–1.48) in the findings. PhenoAgeAccel exhibited a significant additive interaction with genetic susceptibility. Biologically older participants with high genetic risk have a 3.83 (95% CI: 3.51–4.18) folds risk of VTE, a 3.59 (95% CI: 3.21–4.03) folds risk of DVT, and 4.39 (95% CI: 3.88–4.98) folds risk of PE, in comparison to biologically younger participants with low genetic risk. Mediation analyses indicated that PhenoAgeAccel mediated approximately 6% of the association between cancer and VTE, and about 20% of the association between obesity and VTE. Our study indicated that PhenoAgeAccel is significantly associated with higher risk of VTE, and can be combined with genetic risk to improve VTE risk stratification. Additionally, PhenoAgeAccel holds promise as a clinical biomarker for guiding targeted prevention and treatment strategies for VTE.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"74 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992003","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":"CM313 Monotherapy in Patients With Relapsed/Refractory Multiple Myeloma or Marginal Zone Lymphoma: A Multicenter, Phase 1 Dose-Escalation and Dose-Expansion Trial","authors":"Huixing Zhou, Zhongxia Huang, Baijun Fang, Hongmei Jing, Zhongjun Xia, Yuqin Song, Zhen Cai, Gang An, Ling Qin, Li Bao, Xin Li, Yuzhang Liu, Yanrong Wang, Ling Li, Wenming Chen","doi":"10.1002/ajh.27573","DOIUrl":"https://doi.org/10.1002/ajh.27573","url":null,"abstract":"&lt;p&gt;Multiple myeloma (MM) accounts for approximately one-tenth of all hematological malignancies. Although immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have significantly prolonged survival of MM patients, relapses are almost inevitable [&lt;span&gt;1&lt;/span&gt;]. Patients refractory to IMiDs and PIs have a poor prognosis, highlighting the urgency to develop new agents with target specificity in patients with relapsed/refractory MM (RRMM). CD38 is a type 2 transmembrane glycoprotein highly expressed in hematological malignancies and low in normal tissues, permitting CD38-targeting antibody a novel therapeutic option for RRMM. Currently, two anti-CD38 monoclonal antibodies, daratumumab and isatuximab, have been approved for the treatment of RRMM [&lt;span&gt;2-4&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;CM313 is a novel humanized monoclonal antibody with a unique complementarity-determining region sequence that facilitates its high affinity to a spectrum of CD38-positive cells. Preclinical studies showed its comparable in vitro killing activities in target cells and anti-tumor activities with daratumumab, without obvious off-target toxicity [&lt;span&gt;5&lt;/span&gt;]. CM313 also demonstrated encouraging efficacy and favorable safety in patients with immune thrombocytopenia [&lt;span&gt;6&lt;/span&gt;]. Here, we report the first-in-human phase 1 trial of CM313 monotherapy in patients with RRMM and marginal zone lymphoma (MZL).&lt;/p&gt;\u0000&lt;p&gt;This was a multicenter, open-label phase 1 trial consisting of a dose-escalation phase and a dose-expansion phase (NCT04818372). Eligible RRMM patients had a confirmed diagnosis of MM based on the International Myeloma Working Group guidelines, measurable disease, an Eastern Cooperative Oncology Group performance-status score of ≤ 2 points, and prior treatment with IMiDs and PIs. Key exclusion criteria were primary refractory MM, diagnosis of amyloidosis, plasma-cell leukemia, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome, confirmed central nervous system metastases, and prior therapy with anti-CD38 monoclonal antibodies. Detailed eligibility criteria for RRMM and MZL patients are presented in the Supporting Information. Patients in the dose-escalation phase received 9 escalating doses of CM313 intravenously (0.006, 0.06, 0.3, 1.0, 2.0, 4.0, 8.0, 16, and 24 mg/kg) once in a 21-day observation period for dose-limiting toxicities (DLTs), then once weekly (QW) for the next 7 doses, then every 2 weeks (Q2W) for 8 doses, and then every 4 weeks (Q4W) onwards until disease progression or unacceptable toxicities. In the dose-expansion phase, CM313 was administered intravenously at doses of 4.0 and 16 mg/kg QW for 8 doses, then Q2W for 8 doses, and then Q4W thereafter until disease progression or unacceptable toxicities (Figure S1A).&lt;/p&gt;\u0000&lt;p&gt;Primary endpoints were safety and tolerability in the dose-escalation phase and overall response rate (ORR) in the dose-expansion phase. Secondary endpoints included clinical benefi","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"45 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992000","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":"Erdheim-Chester Disease With Significant Response of Large Vessel Disease to Cobimetinib Monotherapy","authors":"Nehaal Ahmed, Jithma P. Abeykoon, Angela Collie, Matthew J. Koster","doi":"10.1002/ajh.27606","DOIUrl":"https://doi.org/10.1002/ajh.27606","url":null,"abstract":"<h2> Conflicts of Interest</h2>\u0000<p>The authors declare no conflicts of interest.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"32 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992001","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}