Simone A Minnie, Olivia G Waltner, Ping Zhang, Shuichiro Takahashi, Nicole S Nemychenkov, Kathleen S Ensbey, Christine R Schmidt, Samuel R W Legg, Melissa Comstock, Julie R Boiko, Ethan Nelson, Shruti S Bhise, Alec B Wilkens, Motoko Koyama, Madhav V Dhodapkar, Marta Chesi, Stanley R Riddell, Damian J Green, Andrew Spencer, Scott N Furlan, Geoffrey R Hill
Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a CD8 T cell subset in the bone marrow tumor microenvironment that, despite an apparent terminally exhausted phenotype (TPHEX ), expressed granzymes, perforin, and IFN-γ. Concurrent gene expression and DNA accessibility revealed that genes encoding these functional proteins correlated with BATF expression and motif accessibility. IFN-γ+ TPHEX effectively killed myeloma with comparable efficacy to transitory effectors, and disease progression correlated with numerical deficits in IFN-γ+ TPHEX ...
April 19, 2024: Science Immunology
Taku Kikuchi, Nobuhiro Tsukada, Kodai Kunisada, Moe Nomura-Yogo, Yuki Oda, Kota Sato, Tomomi Takei, Mizuki Ogura, Yu Abe, Kenshi Suzuki, Tadao Ishida
The introduction of daratumumab has improved treatment outcomes for multiple myeloma (MM). However, infectious complications are a concern in patients receiving daratumumab. Although some reports have explored the association between daratumumab and cytomegalovirus (CMV) infection, most of these have focused on relapsed or refractory cases, and few describe patients with newly diagnosed MM (NDMM). In this study, we retrospectively analyzed CMV infections in 53 patients with NDMM who received daratumumab as induction therapy...
April 19, 2024: International Journal of Hematology
Masataka Sakashita, Naohi Sahara, Jun Aoki, Takashi Matsunaga, Seiichiro Kobayashi, Shinsuke Kitahara, Tomoki Fujii, Nobuhiro Ohno
Despite the emergence of monoclonal antibodies, the prognosis of patients with multiple myeloma (MM) with extramedullary disease remains poor. The present report describes a rare case of daratumumab-refractory MM that was successfully treated with elotuzumab, pomalidomide and dexamethasone. A 66-year-old male patient diagnosed with MM was treated with bortezomib, lenalidomide and dexamethasone, followed by high-dose chemotherapy and autologous stem cell transplantation. Thereafter, the patient was treated with lenalidomide and dexamethasone as maintenance therapy...
June 2024: Oncology Letters
Toshiro Seki, Rikio Suzuki, Shino Ohshima, Yoshiyuki Manabe, Shion Onoue, Yuki Hoshino, Atsushi Yasuda, Ryoji Ito, Hiroshi Kawada, Hitoshi Ishimoto, Takashi Shiina, Yoshie Kametani
Progesterone suppresses several ancient pathways in a concentration-dependent manner. Based on these characteristics, progesterone is considered a candidate anticancer drug. However, the concentration of progesterone used for therapy should be higher than the physiological concentration, which makes it difficult to develop progesterone-based anticancer drugs. We previously developed liposome-encapsulated progesterone (Lipo-P4) with enhanced anticancer effects, which strongly suppressed triple-negative breast cancer cell proliferation in humanized mice...
July 2024: Biochemistry and Biophysics Reports
Sanju Sinha, Rahulsimham Vegesna, Sumit Mukherjee, Ashwin V Kammula, Saugato Rahman Dhruba, Wei Wu, D Lucas Kerr, Nishanth Ulhas Nair, Matthew G Jones, Nir Yosef, Oleg V Stroganov, Ivan Grishagin, Kenneth D Aldape, Collin M Blakely, Peng Jiang, Craig J Thomas, Cyril H Benes, Trever G Bivona, Alejandro A Schäffer, Eytan Ruppin
Tailoring optimal treatment for individual cancer patients remains a significant challenge. To address this issue, we developed PERCEPTION (PERsonalized Single-Cell Expression-Based Planning for Treatments In ONcology), a precision oncology computational pipeline. Our approach uses publicly available matched bulk and single-cell (sc) expression profiles from large-scale cell-line drug screens. These profiles help build treatment response models based on patients' sc-tumor transcriptomics. PERCEPTION demonstrates success in predicting responses to targeted therapies in cultured and patient-tumor-derived primary cells, as well as in two clinical trials for multiple myeloma and breast cancer...
April 18, 2024: Nature Cancer
Hira Mian, Hsien Seow, Amaris K Balitsky, Matthew C Cheung, Anastasia Gayowsky, Jason Tay, Tanya M Wildes, Arleigh McCurdy, Alissa Visram, Irwindeep Sandhu, Rinku Sutradhar
Developing prognostic tools specifically for patients themselves represents an important step in empowering patients to engage in shared decision-making. Incorporating patient-reported outcomes may improve the accuracy of these prognostic tools. We conducted a retrospective population-based study of transplant-ineligible (TIE) patients with multiple myeloma (MM) diagnosed between January 2007 and December 2018. A multivariable Cox regression model was developed to predict the risk of death within 1-year period from the index date...
April 18, 2024: Oncologist
Marta Banchi, Maria Christina Cox, Guido Bocci
Metronomic chemotherapy (mCHEMO), based on frequent, regular administration of low, but pharmacologically active drug doses, optimizes antitumor efficacy by targeting multiple targets and reducing toxicity of antineoplastic drugs. This minireview will summarize preclinical and clinical studies on cytotoxic drugs given at weekly, daily, or at continuous metronomic schedules alone or in combination with novel targeted agents for hematological malignancies, including lymphoma, multiple myeloma, and leukaemia. Most of the preclinical in vitro and in vivo studies have reported a significant benefit of both mCHEMO monotherapy and combinatorial regimens compared with chemotherapy at the maximum tolerated dose...
April 16, 2024: Cancer Letters
Yajing Liu, Yanru Tao, Priscilla S-W Yeung, Mengyan Lu, Jing Liu, Fang Yu, Run-Zhang Shi, Ruben Yiqi Luo
BACKGROUND: Daratumumab (DARA) is a commonly used monoclonal antibody (mAb) drug for the treatment of multiple myeloma (MM). Its appearance as a visible abnormal band in the γ-region of a serum protein electrophoresis (SPEP) gel may interfere with the SPEP result interpretation. With the advantages of portability and rapid testing capabilities, up-conversion fluorescence lateral-flow immunoassay (LFA) can be an ideal solution to detect DARA interference. METHODS: An up-conversion fluorescence LFA strip was designed and constructed to perform semi-quantitative DARA testing in clinical samples...
April 16, 2024: Clinica Chimica Acta; International Journal of Clinical Chemistry
Makoto Shinohara, Masakazu Hashimoto, Yoshihito Kitamura, Keigo Nakashima, Michinori Hamaoka, Masashi Miguchi, Toshihiro Misumi, Nobuaki Fujikuni, Satoshi Ikeda, Yasuhiro Matsugu, Yui Hattori, Takashi Nishisaka, Hideki Nakahara
BACKGROUND: Preoperative diagnosis of gallbladder amyloidosis is usually difficult. In our case, the patient exhibited gallbladder dyskinesia, which led us to suspect cholecystic amyloidosis. We were able to safely perform surgery before cholecystitis onset. CASE PRESENTATION: A 59-year-old male patient with a history of multiple myeloma and cardiac amyloidosis presented to our hospital with a chief complaint of epicardial pain. Abdominal ultrasonography and computed tomography revealed an enlarged gallbladder and biliary sludge without any specific imaging findings of cholecystitis...
April 18, 2024: Surgical Case Reports
Jing Zhao, Xiaoning Wang, Huachao Zhu, Suhua Wei, Hailing Zhang, Le Ma, Wenjuan Zhu
BACKGROUND: Natural killer cells (NKs) may be involved in multiple myeloma (MM) progression. The present study elucidated the correlation between NKs and the progression of MM using single-cell binding transcriptome probes to identify NK cell-related biomarkers. METHODS: Single-cell analysis was performed including cell and subtype annotation, cell communication, and pseudotime analysis. Hallmark pathway enrichment analysis of NKs and NKs-related differentially expressed genes (DEGs) were conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction (PPI) networks...
April 18, 2024: Clinical and Experimental Medicine
Tien-Ru Huang, Chun-Shu Lin, Hsin-Chien Chen
Solitary bone plasmacytoma (SBP) is a rare hematological malignancy that usually occurs in the spine and rarely in the skull. It rarely presents in the skull base, but presenting symptoms are associated with cranial nerve involvement depending on the site of the disease. We present the case of a 61-year-old man with an unusual presentation of hoarseness secondary to vocal fold palsy. Imaging showed a large bony lesion in the temporo-occipital region with involvement of the jugular foramen. Further detailed diagnostic procedures confirmed SBP of the skull base...
April 18, 2024: Ear, Nose, & Throat Journal
Carl Murie, Serdar Turkarslan, Anoop Patel, David G Coffey, Pamela S Becker, Nitin S Baliga
BACKGROUND: Individualized treatment decisions for patients with multiple myeloma (MM) requires accurate risk stratification that takes into account patient-specific consequences of genetic abnormalities and tumor microenvironment on disease outcome and therapy responsiveness. METHODS: Previously, SYstems Genetic Network AnaLysis (SYGNAL) of multi-omics tumor profiles from 881 MM patients generated the mmSYGNAL network, which uncovered different causal and mechanistic drivers of genetic programs associated with disease progression across MM subtypes...
April 3, 2024: medRxiv
Mads Harsløf, Iman Chanchiri, Trine Silkjær, Ulf Christian Frølund, Elena Manuela Teodorescu, Kristina Buchardi Nielsen, Per Ishøy Nielsen, Per Trøllund Pedersen, Katrine Fladeland Iversen, Thomas Lund, Kirsten Grønbæk, Sigrun Thorsteinsdottir, Annette Vangsted, Agoston Gyula Szabo
Lenalidomide maintenance (LM) has shown benefit in progression-free survival (PFS) and overall survival (OS) in clinical trials. LM is the recommended standard of care in patients with newly diagnosed multiple myeloma (MM) after high-dose melphalan and autologous stem cell transplantation (HDM-ASCT). In Denmark, LM has been approved and publicly funded for all patients treated with HDM-ASCT since June 2019. Patients with newly diagnosed MM treated with their first HDM-ASCT between June 2019 and March 2022 were included and followed until data cut-off in June 2023...
April 2024: EJHaem
Catherine Lecat, Eileen M Boyle, Daniel Hughes, Lydia Lee, Dean Smith, Ceri Bygrave, Karthik Ramasamy, Kwee Yong
No abstract text is available yet for this article.
April 2024: EJHaem
Rahul Gujarathi, Manisha Rakesh Lakhanpal, Nikhila Chelikam, Divesh Manjani, Simmy Lahori, Sai Anusha Akella, Prashanth Gumpu Shivashankar, Francis Vino Dominic Savio, Abdirazak Ibrahim Ali, Navyatha Annareddy, Aryak Singh, Lokesh Manjani, Prasanthi Vanga, Avinash Adiga
Multiple myeloma (MM), constituting 10% of hematological malignancies, poses significant morbidity and mortality, especially with skeletal involvement. Bisphosphonate use in MM may lead to severe hypocalcemia due to vitamin D deficiency (VDD), exacerbating bone marrow plasma cell burden. We aimed to assess VDD prevalence and its impact on outcomes in MM patients. A retrospective cross-sectional analysis (2008-2018) of nationwide inpatient data identified adult MM hospitalizations with VDD using ICD-10-CM codes...
April 17, 2024: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Qiao Yang, Fujing Zhang, Zhixin Hao, Junling Zhuang, Li Huo
An 83-year-old woman with newly diagnosed multiple myeloma (MM) was enrolled in our 68Ga-pentixather and 68Ga-pentixafor PET/CT trial for evaluation of tumor burden. 68Ga-pentixather PET/CT detected more focal bone lesions, and the uptake levels of focal bone lesions on 68Ga-pentixather PET/CT were higher than those on 68Ga-pentixafor PET/CT. This suggests that 68Ga-pentixather PET/CT may be an alternative imaging modality and more sensitive in detecting MM lesions than 68Ga-pentixafor PET/CT.
April 17, 2024: Clinical Nuclear Medicine
Attaya Suvannasankha, Nizar Bahlis, Suzanne Trudel, Katja Weisel, Christian Koenecke, Albert Oriol, Peter M Voorhees, Aranzazu A Alonso, Natalie S Callander, María-Victoria Mateos, Nishitha Reddy, Shawn Hakim, John LaMacchia, Nashita Patel, Danaé Williams, Roxanne C Jewell, Xiangdong Zhou, Ira Gupta, Joanna Opalinska, Ajay K Nooka
BACKGROUND: Belantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM. METHODS: DREAMM-4 (NCT03848845) was an open-label, single-arm, phase 1/2 study divided into dose-escalation (part 1) and dose-expansion (part 2) phases...
April 17, 2024: Cancer
Sophia Stock, Luisa Fertig, Adrian Gottschlich, Janina Dörr, Florian Märkl, Lina Majed, Vivien D Menkhoff, Ruth Grünmeier, Kai Rejeski, David M Cordas Dos Santos, Sebastian Theurich, Michael von Bergwelt-Baildon, Stefan Endres, Marion Subklewe, Sebastian Kobold
In multiple myeloma (MM), B cell maturation antigen (BCMA)-directed CAR T cells have emerged as a novel therapy with potential for long-term disease control. Anti-BCMA CAR T cells with a CD8-based transmembrane (TM) and CD137 (41BB) as intracellular costimulatory domain are in routine clinical use. As the CAR construct architecture can differentially impact performance and efficacy, the optimal construction of a BCMA-targeting CAR remains to be elucidated. Here, we hypothesized that varying the constituents of the CAR structure known to impact performance could shed light on how to improve established anti-BCMA CAR constructs...
April 17, 2024: Cancer Immunology, Immunotherapy: CII
Ayse Nilgun Kul, Bahar Ozturk Kurt
Trace elements are essential micronutrients for the human body. Their roles are indispensable, as they are involved in a wide range of vital biological processes. In this study, we aimed to evaluate alterations in trace elements in the blood and bone marrow serum of patients with newly diagnosed multiple myeloma (NMM). The levels of zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), magnesium (Mg), selenium (Se), arsenic (As), boron (B), nickel (Ni), silicon (Si) and chromium (Cr) were analyzed in the venous blood samples of the patient group comprising 70 patients with NMM (41 males and 29 females) and compared to those in the control group comprising 30 individuals (18 males and 12 females)...
April 17, 2024: Clinical and Experimental Medicine
Charalampos Charalampous, Darshi Shah, Shaji Kumar, Rajshekhar Chakraborty
Venous thromboembolism (VTE) poses a significant challenge in the context of multiple myeloma, with an incidence of up to 10% in newly diagnosed patients and varying frequency in the relapsed/refractory setting. Accurate VTE risk assessment and personalized thromboprophylaxis strategies are important parts of supportive care in myeloma. There are three validated risk assessment models for prediction of VTE risk in newly diagnosed myeloma-SAVED, IMPEDE-VTE, and PRISM. In this review, we delve into the practical applications of VTE risk prediction models in the context of current therapies...
April 17, 2024: Annals of Hematology
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