Review
Biochemistry & Molecular Biology
Roisin McAvera, John Quinn, Philip Murphy, Siobhan Glavey
Summary: Extramedullary multiple myeloma (EMD) is an aggressive form of multiple myeloma that occurs when malignant plasma cells become independent of the bone marrow microenvironment. The underlying mechanisms of bone marrow escape and EMD driver events are not well understood, but there is increasing focus on high-risk cytogenetic abnormalities, gene signatures, mutations in RAS signalling pathways, and changes in epigenetic regulation. This review aims to summarize and discuss the current knowledge about the genetic background of EMD in MM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Radhika Bansal, Sagar Rakshit, Shaji Kumar
Summary: Extramedullary multiple myeloma (EMD) is a challenging disease from therapeutic and biological perspectives, with unclear pathogenetic mechanisms. In the era of novel agents, there is a rising incidence of EMD, but lack of standard treatment approaches.
BLOOD CANCER JOURNAL
(2021)
Article
Cell Biology
Limei Zhang, Shuzhao Chen, Weida Wang, Yun Wang, Yang Liang
Summary: A predictive model based on six clinical variables was developed to predict the survival of patients with primary extramedullary multiple myeloma (EMM), showing good prognostic performance.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Dimitrios Strauss, Christos Sachpekidis, Ulrike Dapunt, Hartmut Goldschmidt, Antonia Dimitrakopoulou-Strauss
Summary: A 73-year-old man with multiple myeloma was found to have bilateral synchronous testicular manifestation during his F-18-FDG PET/CT scan. This rare finding was confirmed by histopathology after orchiectomy. Only a small percentage of multiple myeloma cases show testicular manifestation, and the optimal therapy management for such cases is still unclear.
CLINICAL NUCLEAR MEDICINE
(2023)
Review
Oncology
Joan Blade, Meral Beksac, Jo Caers, Artur Jurczyszyn, Marie Von Lilienfeld-Toal, Philippe Moreau, Leo Rasche, Laura Rosinol, Saad Z. Usmani, Elena Zamagni, Paul Richardson
Summary: Extramedullary involvement is an aggressive form of multiple myeloma, with varied typical sites and incidence rates. Patients with EMD have poor prognosis and lower treatment efficacy. The lack of prospective studies limits strong recommendations for treatment approaches.
BLOOD CANCER JOURNAL
(2022)
Article
Oncology
JingSong He, XiaoYan Yue, DongHua He, Yi Zhao, Yang Yang, GaoFeng Zheng, Enfan Zhang, XiaoYan Han, WenJun Wu, Li Yang, Jing Chen, Zhen Cai
Summary: This study found that multiple sites of EMB and/or EME are independent poor prognostic factors for newly diagnosed MM patients treated with bortezomib-based regimens, while a single site of EMB does not affect patients' survival. Multiple sites of EMB and/or EME are prognostic predictors affecting PFS and OS in newly diagnosed MM patients.
FRONTIERS IN ONCOLOGY
(2021)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Seda Gulbahar Ates, Gulin Ucmak
Summary: Multiple myeloma is a hematologic malignancy characterized by uncontrolled clonal proliferation of plasma cells, and gastrointestinal involvement is a rare but aggressive biological sign.
CLINICAL NUCLEAR MEDICINE
(2022)
Article
Oncology
Juan Xu, Nanhui Yu, Pan Zhao, Fangfang Wang, Jingcao Huang, Yushan Cui, Hong Ding, Yan Yang, Yuhan Gao, Ling Pan, Hong Chang, Yu Wu, Bing Xiang, Yuping Gong, Xiao Shuai, Li Hou, Liping Xie, Ting Niu, Ting Liu, Li Zhang, Weiping Liu, Wenyan Zhang, Ying Qu, Wei Lin, Yimin Zhu, Sha Zhao, Yuhuan Zheng
Summary: The study revealed lower MIF expression in extramedullary multiple myeloma (EMM) compared to intramedullary multiple myeloma (IMM), with MIFHigh cells in IMM showing higher proliferation and MIFLow cells in EMM being more quiescent and enriched in ribosomal protein genes. In vivo differential regulation of MIF expression in MM was identified, suggesting a potential pathogenic role of MIF in the extramedullary spread of disease.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Martin Stork, Sabina Sevcikova, Jiri Minarik, Petra Krhovska, Jakub Radocha, Lenka Pospisilova, Lucie Brozova, Jiri Jarkovsky, Ivan Spicka, Jan Straub, Petr Pavlicek, Alexandra Jungova, Tomas Jelinek, Viera Sandecka, Vladimir Maisnar, Roman Hajek, Ludek Pour
Summary: The study identified younger age, high lactate dehydrogenase levels, extensive osteolytic activity, immunoglobulin A or the non-secretory type of MM as main risk factors for secondary EMD development in MM patients. Additionally, MM patients with specific risk factors associated with secondary EMD development were found to have a more aggressive disease course before the development of secondary EMD.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Saurabh Zanwar, Matthew Ho, Yi Lin, Prashant Kapoor, Moritz Binder, Francis K. Buadi, Angela Dispenzieri, David Dingli, Amie Fonder, Morie A. Gertz, Wilson Gonsalves, Suzanne R. Hayman, Yi Hwa, Miriam Hobbs, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Eli Muchtar, Rahma Warsame, Dragan Jevremovic, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar
Summary: Extramedullary multiple myeloma (EMM) can occur at initial diagnosis or disease relapse, and is associated with aggressive progression. There is limited data on the optimal therapy for EMM, and this remains an area of unmet clinical need.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Oncology
Stefan Forster, Ramin Radpour
Summary: Multiple myeloma is a common malignant disease of plasma cells, and current treatments include chemotherapy, immunomodulatory agents, and monoclonal antibodies. The tumor microenvironment plays a crucial role in the development and progression of multiple myeloma, and understanding how different components of the bone marrow promote plasma cell dissemination is important for preventing the spread of the disease to other sites.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Yating Li, Zhengxu Sun, Xiaoyan Qu
Summary: This review summarizes the recent advances in the treatment of extramedullary disease (EMD) in multiple myeloma (MM) patients. Bortezomib-based therapy and immunomodulatory drugs have shown efficacy, while marizomib has advantages in treating CNS-MM. Isatuximab and selinexor also exhibit activity. However, the benefits of novel drugs for EMD patients are limited.
TRANSLATIONAL ONCOLOGY
(2022)
Article
Cell Biology
Weilong Zhang, Chaoling Wu, Shuang Geng, Jing Wang, Changjian Yan, Xiannian Zhang, Jia-jia Zhang, Fan Wu, Yuhong Pang, Yuping Zhong, Jianbin Wang, Wei Fu, Xin Huang, Wenming Wang, Xiaoqing Lyu, Yanyi Huang, Hongmei Jing
Summary: According to Nowell's theory of clonal evolution, cancers originate from a single cell. The enrichment of aggressive clones and the heterogeneity of tumors are caused by genomic instability and environmental selection. Multiple myeloma is a relapse plasma cell cancer generated from bone marrow. Despite previous research on multiple myeloma pathogenesis, heterogeneity remains poorly understood. In this study, single cell RNA sequencing was conducted on multiple myeloma patients to investigate the role of FAM46C in tumor heterogeneity and extramedullary metastasis prediction.
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Mehmet Onur Demirkol, Ahu Ozkan, Burcu Ucar, Hans-Juergen Wester, Burhan Ferhanoglu
Summary: The national clinical protocol of Lu-177-CXCR4 therapy showed promising clinical response in heavily pretreated patients with advanced multiple myeloma, with acceptable radiation dose limits.
CLINICAL NUCLEAR MEDICINE
(2021)
Article
Hematology
Yating Li, Jiamei Ji, Hua Lu, Jianyong Li, Xiaoyan Qu
Summary: This retrospective study assessed the efficacy of pomalidomide-based therapy in the treatment of EMD and found that it showed efficacy in these previously treated EMD patients.
Article
Oncology
Thomas Martin, Saad Z. Usmani, Jesus G. Berdeja, Mounzer Agha, Adam D. Cohen, Parameswaran Hari, David Avigan, Abhinav Deol, Myo Htut, Alexander Lesokhin, Nikhil C. Munshi, Elizabeth O'Donnell, A. Keith Stewart, Jordan M. Schecter, Jenna D. Goldberg, Carolyn C. Jackson, Tzu-Min Yeh, Arnob Banerjee, Alicia Allred, Enrique Zudaire, William Deraedt, Yunsi Olyslager, Changwei Zhou, Lida Pacaud, Deepu Madduri, Andrzej Jakubowiak, Yi Lin, Sundar Jagannath
Summary: PURPOSECARTITUDE-1, a phase Ib/II study, evaluated the safety and efficacy of Ciltacabtagene Autoleucel in heavily treated patients with relapsed/refractory multiple myeloma. The study showed early, deep, and durable responses at 12 months, with updated results at 2 years. Patients received a single infusion of Ciltacabtagene Autoleucel and responses were assessed.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
David M. Foureau, Barry A. Paul, Fei Guo, Edward H. Lipford, Kateryna Fesenkova, Elise Tjaden, Kendra Drummond, Manisha Bhutani, Shebli Atrash, Ami Ndiaye, Cindy Varga, Peter M. Voorhees, Saad Z. Usmani
Summary: To optimize specimen adequacy, our institution standardized technical 1st pull bone marrow aspirates (BMA) for minimal residual disease (MRD) testing in multiple myeloma. We achieved an analytical assay input of 10 million nucleated cells for 97.5% of specimens, allowing us to routinely achieve 1-2 x 10 -6 analytic sensitivity.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Oncology
Adam D. Cohen, Parameswaran Hari, Myo Htut, Jesus G. Berdeja, Saad Z. Usmani, Deepu Madduri, Yunsi Olyslager, Jenna D. Goldberg, Jordan M. Schecter, Carolyn C. Jackson, Katharine S. Gries, John M. Fastenau, Satish Valluri, William Deraedt, Muhammad Akram, Rebecca Crawford, Ross Morrison, Lynda Doward, Kate Morgan, Silene ten Seldam, Andrzej Jakubowiak, Sundar Jagannath
Summary: Ciltacabtagene autoleucel (cilta-cel) is a CAR-T cell therapy that has shown efficacy in patients with relapsed/refractory multiple myeloma and improvements in health-related quality of life. Patient perspectives on cilta-cel treatment provide additional context to clinical outcomes and the majority of patients reported that their expectations were met or exceeded.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Medicine, General & Internal
Tom Martin, Saad Z. Usmani, Jordan M. Schecter, Tito Roccia, Carolyn C. Jackson, William Deraedt, Tzu-Min Yeh, Arnob Banerjee, Lida Pacaud, Ashraf Garrett, Meaghan Bartlett, Anja Haltner, Suzy Van Sanden, Joris Diels, Satish Valluri, Imtiaz A. Samjoo
Summary: This study compared the efficacy of cilta-cel and ide-cel in treating RRMM patients using the latest clinical trial data. The results demonstrated that cilta-cel had significantly improved overall response rate, complete response rate, duration of response, progression-free survival, and overall survival compared to ide-cel.
CURRENT MEDICAL RESEARCH AND OPINION
(2023)
Article
Hematology
Matthew J. J. Pianko, Timothy Tiutan, Andriy Derkach, Jessica Flynn, Steven P. P. Salvatore, Insara Jaffer-Sathick, Adriana C. C. Rossi, Oscar Lahoud, Malin Hultcrantz, Urvi A. A. Shah, Kylee Maclachlan, David J. J. Chung, Gunjan L. L. Shah, Heather J. J. Landau, Neha Korde, Sham Mailankody, Alexander M. M. Lesokhin, Carlyn Tan, Michael Scordo, Edgar A. A. Jaimes, Sergio A. A. Giralt, Saad Usmani, Hani Hassoun
Summary: This retrospective analysis of patients with monoclonal immunoglobulin deposition disease (MIDD) demonstrates that renal response can be captured using both estimated glomerular filtration rate (eGFR) and proteinuria criteria. Most patients achieved a very good partial hematologic response with treatment. Isolated proteinuria may be an early manifestation of MIDD associated with reversible renal damage. Baseline eGFR predicts renal response and survival. Further prospective studies with uniform renal response criteria are needed to optimize the management of MIDD.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Oliver Van Oekelen, Karthik Nath, Tarek H. Mouhieddine, Tasmin Farzana, Adolfo Aleman, David T. Melnekoff, Yogita Ghodke-Puranik, Gunjan L. Shah, Alexander Lesokhin, Sergio Giralt, Santiago Thibaud, Adriana Rossi, Cesar Rodriguez, Larysa Sanchez, Joshua Richter, Shambavi Richard, Hearn J. Cho, Ajai Chari, Saad Z. Usmani, Sundar Jagannath, Urvi A. Shah, Sham Mailankody, Samir Parekh
Summary: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR T) therapy has shown remarkable efficacy in relapsed/refractory multiple myeloma patients. However, most patients eventually relapse despite high initial response rates. This study analyzed the salvage treatments and outcomes of patients with disease recurrence after BCMA-directed CAR T therapy.
Article
Oncology
Doris K. Hansen, Surbhi Sidana, Lauren C. Peres, Christelle Colin Leitzinger, Leyla Shune, Alexandria Shrewsbury, Rebecca Gonzalez, Douglas W. Sborov, Charlotte Wagner, Danai Dima, Hamza Hashmi, Mehmet H. Kocoglu, Shebli Atrash, Gary Simmons, Nilesh Kalariya, Christopher Ferreri, Aimaz Afrough, Ankit Kansagra, Peter Voorhees, Rachid Baz, Jack Khouri, Melissa Alsina, Joseph McGuirk, Frederick L. Locke, Krina K. Patel
Summary: A retrospective analysis showed that the safety and efficacy of standard-of-care ide-cel therapy in RRMM patients were similar to those seen in the phase II KarMMa trial, despite most patients not meeting the trial eligibility criteria.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Al-Ola Abdallah, Zahra Mahmoudjafari, Nausheen Ahmed, Wei Cui, Leyla Shune, Joseph McGuirk, Meera Mohan, Ghulam Rehman Mohyuddin, Aimaz Afrough, Omar Alkharabsheh, Shebli Atrash
Summary: This study analyzes the clinical efficacy of daratumumab retreatment in patients with daratumumab-refractory multiple myeloma, and suggests that combination therapy of daratumumab with other anti-myeloma drugs can generate responses in these patients.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Shebli Atrash, Myra Robinson, Alankrita Taneja, Barry Paul, Kristen Cassetta, Ami Ndiaye, Cindy Varga, Jared Block, Edward H. Lipford, Elton T. Smith, Chad M. McCall, Virginia Thurston, David Foureau, Saad Z. Usmani, Peter M. Voorhees, Manisha Bhutani
Summary: This study investigated the relationship between Ki-67 expression and survival outcomes in newly diagnosed multiple myeloma (MM) patients. The results demonstrated that a high Ki-67 index (>5%) was associated with worse overall survival (OS) and progression-free survival (PFS), suggesting that Ki-67 could serve as an independent prognostic marker for MM patients.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Shebli Atrash, Aytaj Mammadzadeh, Fulei Peng, Omar Alkharabsheh, Aimaz Afrough, Wei Cui, Zahra Mahmoudjafari, Al-Ola Abdallah, Hamza Hashmi
Summary: BCMA-targeted therapy has changed the outcomes of penta-refractory myeloma, leading to better overall survival. However, the treatment resistance of penta-refractory myeloma still needs to be overcome, and more novel treatment options are needed.
Article
Oncology
Thomas G. Martin, Deepu Madduri, Lida Pacaud, Saad Z. Usmani
Summary: Cilta-cel, a BCMA-targeting CAR T-cell therapy, has been approved in the USA and EU for multiple myeloma patients who have relapsed or refractory disease. It showed a high response rate and promising progression-free survival in clinical trials, with manageable adverse events. Further research is needed to explore its efficacy and safety in earlier lines of therapy and optimal sequencing in a complex treatment landscape.
Article
Oncology
Aimaz Afrough, Shebli Atrash, Barry Paul, Evguenia Ouchveridze, Nausheen Ahmed, Zahra Mahmoudjafari, Anam Bashir, Omar Alkharabsheh, Hamza Hashmi, Al-Ola Abdallah
Summary: This study compared the safety and efficacy of different medication combinations for relapsed or refractory multiple myeloma. The analysis showed that one combination (DPd) had a better response to treatment, but both combinations had similar progression-free survival and overall survival rates. The study highlights the importance of considering patient and disease characteristics when selecting salvage treatments.
Article
Oncology
Barry Paul, Michaela Liedtke, Jack Khouri, Robert Rifkin, Mitul D. Gandhi, Andrew Kin, Moshe Y. Levy, Rebecca Silbermann, Francesca Cottini, Douglas W. Sborov, Irwindeep Sandhu, Lyssa Villarreal, Michael Murphy, Lin Gu, Ann Chen, Nishanthan Rajakumaraswamy, Saad Z. Usmani
Summary: Magrolimab is a monoclonal antibody that blocks the CD47 signal on tumor cells. CD47 is overexpressed in multiple myeloma and contributes to its development. Preclinical studies have shown that blocking CD47 activates macrophages, leading to the elimination of myeloma cells. This phase II study investigates the combination of magrolimab with standard myeloma therapies in patients with relapsed/refractory MM.
Review
Oncology
Manisha Bhutani, Brandon J. Blue, Craig Cole, Ashraf Z. Badros, Saad Z. Usmani, Ajay K. Nooka, Leon Bernal-Mizrachi, Joseph Mikhael
Summary: This review examines the disparities in incidence, diagnosis, treatment access, clinical trial participation, and healthcare utilization that negatively impact outcomes for African American patients with multiple myeloma. It emphasizes the role of healthcare providers in addressing these disparities by considering historical, sociocultural, individual, and disease-related factors. The review provides insights into both biological and non-biological disparities, barriers to clinical care, and best practices for ensuring that African American patients receive optimal care.
BLOOD CANCER JOURNAL
(2023)
Article
Oncology
Anish K. Simhal, Kylee H. Maclachlan, Rena Elkin, Jiening Zhu, Larry Norton, Joseph O. Deasy, Jung Hun Oh, Saad Z. Usmani, Allen Tannenbaum
Summary: The study investigates the global interactions in multiple myeloma (MM) using a protein interaction network and a large dataset. The analysis reveals complex immune dysregulation associated with shorter survival.
BLOOD CANCER JOURNAL
(2023)
