Article
Cell Biology
Tyler Lussier, Natalie Schoebe, Sabine Mai
Summary: Smoldering multiple myeloma, a precursor to multiple myeloma, can be stratified using clinical measurement-based and genetics-based risk stratification models. Accurately distinguishing high-risk patients is important for improved outcomes with early treatment.
Review
Hematology
Iuliana Vaxman, Morie A. Gertz
Summary: This review discusses the current standard of care for smoldering multiple myeloma and efforts to understand its progression to active multiple myeloma. Two patient cases are presented to illustrate that sometimes patients can undergo observation only, even when they exceed criteria for high-risk smoldering multiple myeloma.
Review
Oncology
Natalia Kreiniz, Morie A. Gertz
Summary: Smoldering multiple myeloma (SMM) is an asymptomatic condition with varying risks of progression. Risk stratification models like Mayo-2018 and IWWG are commonly used, and the personalized risk assessment tool PANGEA has been introduced. New markers, including genomic and immune characteristics, are being investigated for SMM progression. Treatment strategies for high-risk SMM have shown promising results, but adverse effects may occur in asymptomatic patients. This review aims to provide a comprehensive understanding of SMM progression risk.
LEUKEMIA & LYMPHOMA
(2023)
Article
Biochemistry & Molecular Biology
Sigrun Thorsteinsdottir, Gauti K. K. Gislason, Thor Aspelund, Saemundur Rognvaldsson, Jon Porir Oskarsson, Guorun A. Siguroardottir, Asdis R. Thordardottir, Brynjar Vidarsson, Pall T. Onundarson, Bjarni A. A. Agnarsson, Margret Sigurdardottir, Ingunn Thorsteinsdottir, Isleifur Olafsson, Elias Eythorsson, Asbjoern Jonsson, Oscar Berlanga, Malin Hulcrantz, Brian G. M. Durie, Thorvardur J. Love, Stephen Harding, Ola Landgren, Sigurdur Y. Kristinsson
Summary: This study investigated the epidemiological characteristics of smoldering multiple myeloma (SMM) in the general population of Iceland. The prevalence of SMM in individuals 40 years or older was found to be 0.53%, with higher rates in men (0.67%) than in women (0.39%). The high prevalence of SMM has important implications for future treatment policies in multiple myeloma.
Review
Medicine, General & Internal
Niccolo Bolli, Nicola Sgherza, Paola Curci, Rita Rizzi, Vanda Strafella, Mario Delia, Vito Pier Gagliardi, Antonino Neri, Luca Baldini, Francesco Albano, Pellegrino Musto
Summary: Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell neoplasm with a wide range of clinical outcomes, posing challenges for treatment and prognostication. The potential benefits of early treatment for high-risk SMM patients still need further confirmation through independent studies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Urology & Nephrology
Raphael Kormann, Claire Pouteil-Noble, Clotilde Muller, Bertrand Arnulf, Denis Viglietti, Rebecca Sberro, Johnny Sayegh, Antoine Durrbach, Jacques Dantal, Sophie Girerd, Vincent Pernin, Laetitia Albano, Eric Rondeau, Julie Peltier
Summary: Selected MM patients may benefit from kidney transplantation but require careful surveillance for complications and MM progression.
CLINICAL KIDNEY JOURNAL
(2021)
Article
Oncology
S. Vincent Rajkumar, Shaji Kumar, Sagar Lonial, Maria Victoria Mateos
Summary: Smoldering multiple myeloma (SMM) is an asymptomatic condition between MGUS and MM. There is no reliable method to distinguish these two groups of patients. High-risk SMM patients should receive specific treatment or participate in clinical trials, while low-risk SMM patients can be observed without treatment.
BLOOD CANCER JOURNAL
(2022)
Article
Oncology
Rosalinda Termini, David Zihala, Evangelos Terpos, Albert Perez-Montana, Tomas Jelinek, Marc Raab, Niels Weinhold, Elias K. Mai, Anna Luise Grab, Jill Corre, Francois Vergez, Antonio Sacco, Marco Chiarini, Viviana Giustini, Alessandra Tucci, Sara Rodriguez, Cristina Moreno, Cristina Perez, Catarina Maia, Esperanza Martin-Sanchez, Camilla Guerrero, Cirino Botta, Juan-Jose Garces, Aitziber Lopez, Luis-Esteban Tamariz-Amador, Felipe Prosper, Joan Bargay, Maria-Elena Cabezudo, Enrique M. Ocio, Roman Hajek, Joaquin Martinez-Lopez, Fernando Solano, Rebeca Iglesias, Artur Paiva, Catarina Geraldes, Helena Vitoria, Clara Gomez, Felipe De Arriba, Heinz Ludwig, Antoni Garcia-Guinon, Maria Casanova, Adrian Alegre, Valentin Cabanas, Maialen Sirvent, Albert Oriol, Javier de la Rubia, Jose-Angel Hernandez-Rivas, Luis Palomera, Maria Sarasa, Pablo Rios, Noemi Puig, Maria-Victoria Mateos, Juan Flores-Montero, Alberto Orfao, Hartmut Goldschmidt, Herve Avet-Loiseau, Aldo M. Roccaro, Jesus F. San-Miguel, Bruno Paiva
Summary: This study suggests that measuring circulating tumor cells (CTCs) in peripheral blood is more accurate than bone marrow plasma cells (BM PCs) for assessing tumor burden in smoldering multiple myeloma (SMM). Combining the 20/2/0.015 model with an immune risk score based on specific immune cell percentages allows for better risk stratification of SMM patients.
CLINICAL CANCER RESEARCH
(2022)
Article
Education, Scientific Disciplines
Alissa Visram, Joselle Cook, Rahma Warsame
Summary: The traditional approach for smoldering myeloma (SMM) has been observation without treatment, but advancements in definitions and risk models have posed a challenge for determining treatment strategies for high-risk SMM patients. Recent studies indicate that early intervention can improve progression-free survival for high-risk SMM patients, offering new insights into clinical management.
HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM
(2021)
Editorial Material
Medicine, General & Internal
Magda Zanelli, Stefano Ricci, Maurizio Zizzo, Francesca Sanguedolce, Federica De Giorgi, Andrea Palicelli, Giovanni Martino, Stefano Ascani
Summary: A 79-year-old woman presented with peripheral eosinophilia, with a history of colonic polyposis and subsequent right hemicolectomy. Laboratory tests revealed mild macrocitic anaemia, elevated beta 2 microglobulin and serum tryptase levels, and the presence of IgA/kappa monoclonal protein and Bence-Jones protein. Bone marrow biopsy showed two neoplastic components - mast cells and plasma cells, with molecular analysis demonstrating mutations and chromosomal abnormalities. The rare coexistence of systemic mastocytosis and multiple myeloma led to treatment with midostaurin therapy.
Article
Multidisciplinary Sciences
Eileen M. Boyle, Shayu Deshpande, Ruslana Tytarenko, Cody Ashby, Yan Wang, Michael A. Bauer, Sarah K. Johnson, Christopher P. Wardell, Sharmilan Thanendrarajan, Maurizio Zangari, Thierry Facon, Charles Dumontet, Bart Barlogie, Arnaldo Arbini, Even H. Rustad, Francesco Maura, Ola Landgren, Fenghuang Zhan, Frits van Rhee, Carolina Schinke, Faith E. Davies, Gareth J. Morgan, Brian A. Walker
Summary: The study found that smoldering myeloma (SMM) has fewer NRAS and FAM46C mutations, as well as fewer adverse translocations, when compared to newly diagnosed myeloma. KRAS mutations are associated with a shorter time to progression. Changes in clonal structure, branching evolutionary patterns, and other genetic mechanisms may underlie the transition from SMM to MM, providing insights for early intervention strategies.
NATURE COMMUNICATIONS
(2021)
Review
Hematology
Hashim Mann, Vatsala Katiyar, Cindy Varga, Raymond L. Comenzo
Summary: This review provides insights into the pathobiological basis of smoldering multiple myeloma and the progress in its treatment options, as well as a pragmatic approach to its modern-day management.
Article
Medicine, Research & Experimental
Fei Fei, Tingting Ma, Xuan Zhou, Meihong Zheng, Bei Cao, Juan Li
Summary: This study identified distinct metabolic features between multiple myeloma patients and healthy volunteers, especially in bone marrow, with disruptions in glutamate metabolism and carnitine synthesis being unique in multiple myeloma patients. Aspartate in plasma was highlighted as a top candidate biomarker for diagnosis, while threonine was identified as a preferential biomarker for risk prediction, showing significant relations with various risk indexes of multiple myeloma in both bone marrow and plasma.
Article
Immunology
Ignacio Isola, Fara Braso-Maristany, David F. Moreno, Mari-Pau Mena, Aina Oliver-Calders, Laia Pare, Luis Gerardo Rodriguez-Lobato, Beatriz Martin-Antonio, Maria Teresa Cibeira, Joan Blade, Laura Rosinol, Aleix Prat, Ester Lozano, Carlos Fernandez de Larrea
Summary: Analysis of the immune bone marrow microenvironment in patients with smoldering multiple myeloma (SMM) revealed upregulation of cytotoxic genes, but also activation of inhibitory immune checkpoints which may lead to impaired effector function. Patients were classified into distinct clusters based on immune composition and activation markers, with cluster 2 showing exhausted cytotoxic cells associated with higher progression risk. Overexpression of TNF superfamily members was also linked to shorter progression free survival in this study.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Marta Lionetti, Matteo C. Da Via, Francesco Albano, Antonino Neri, Niccolo Bolli, Pellegrino Musto
Summary: This review highlights the importance of risk stratification and the role of the microenvironment in the progression of smoldering multiple myeloma (SMM). While current risk stratification models rely on indirect markers and may miss cases where clonal cells have turned malignant but not yet expanded significantly, advancements in next-generation sequencing techniques offer potential for improved prognostication. The review also discusses the genomic landscape of SMM, intrinsic factors affecting progression, and potential clinical implications of these biological insights.
Article
Hematology
Marcella Kaddoura, Moritz Binder, David Dingli, Francis K. Buadi, Martha Q. Lacy, Morie A. Gertz, Angela Dispenzieri, Prashant Kapoor, Lisa Hwa, Amie Fonder, Miriam Hobbs, Suzanne Hayman, Nelson Leung, Ronald S. Go, Yi Lin, Wilson Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A. Kyle, Vincent Rajkumar, Shaji Kumar
Summary: Achieving a complete response (CR) within 2 years from diagnosis in multiple myeloma (MM) improves survival outcomes and neutralizes the impact of fluorescence in situ hybridization (FISH) and International Staging System (ISS) risk.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Hematology
Aldo A. Acosta-Medina, Ann M. Moyer, Ronald S. Go, Maria Alice V. Willrich, Fernando C. Fervenza, Nelson Leung, Christianne Bourlon, Jeffrey L. Winters, Grant M. Spears, Sandra C. Bryant, Meera Sridharan
Summary: Eculizumab is effective for complement-mediated thrombotic microangiopathy. Discontinuation of therapy does not universally lead to relapse. This study aimed to assess the role of complement genetic variants in predicting recurrence after Eculizumab withdrawal. A total of 280 patients were included, with CFH and MCP/CD46 being the most commonly identified genetic variants. The relapse rate after discontinuation was 29.6%, with CFH and MCP/CD46 variants in canonical splice regions having the highest relapse rates.
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
Hematology
Matthew Ho, Saurabh Zanwar, Francis K. Buadi, Sikander Ailawadhi, Jeremy Larsen, Leif Bergsagel, Moritz Binder, Asher Chanan-Khan, David Dingli, Angela Dispenzieri, Rafael Fonseca, Morie A. Gertz, Wilson Gonsalves, Ronald S. Go, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Eli Muchtar, Vivek Roy, Taimur Sher, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi L. Hwa, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar
Summary: Patients with multiple myeloma have a lower efficacy from COVID-19 vaccination and a high rate of mortality from COVID-19 in hospitalized patients. The study found a relatively low infection rate but a quarter of the COVID-19 infections were severe. Treatment with CD38 antibody, cardiac and pulmonary comorbidities were independent predictors for ICU admission. Cardiac comorbidity was an independent predictor of mortality, while MM/AL in remission was associated with lower mortality.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
Marco Dicanio, Matteo Giaccherini, Alyssa Clay-Gilmour, Angelica Macauda, Juan Sainz, Mitchell J. Machiela, Malwina Rybicka-Ramos, Aaron D. Norman, Agata Tyczynska, Stephen J. Chanock, Torben Barington, Shaji K. Kumar, Parveen Bhatti, Wendy Cozen, Elizabeth E. Brown, Anna Suska, Eva K. Haastrup, Robert Z. Orlowski, Marek Dudzinski, Ramon Garcia-Sanz, Marcin Kruszewski, Joaquin Martinez-Lopez, Katia Beider, Elzbieta Iskierka-Jazdzewska, Matteo Pelosini, Sonja Berndt, Malgorzata Razny, Krzysztof Jamroziak, S. Vincent Rajkumar, Artur Jurczyszyn, Annette Juul Vangsted, Pilar Garrido Collado, Ulla Vogel, Jonathan N. Hofmann, Mario Petrini, Aleksandra Butrym, Susan L. Slager, Elad Ziv, Edyta Subocz, Graham G. Giles, Niels Frost Andersen, Grzegorz Mazur, Marzena Watek, Fabienne Lesueur, Michelle A. T. Hildebrandt, Daria Zawirska, Lene Hyldahl Ebbesen, Herlander Marques, Federica Gemignani, Charles Dumontet, Judit Varkonyi, Gabriele Buda, Arnon Nagler, Agnieszka Druzd-Sitek, Xifeng Wu, Katalin Kadar, Nicola J. Camp, Norbert Grzasko, Rosalie G. Waller, Celine Vachon, Federico Canzian, Daniele Campa
Summary: The aim of this study was to identify novel pleiotropic variants involved in multiple myeloma (MM) risk. Through analysis of 28,684 single nucleotide polymorphisms (SNPs), DNAJB4-rs34517439-A was found to be associated with an increased risk of developing MM.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Hematology
Karan L. Chohan, Jonas Paludo, Nishanth Vallumsetla, Dirk Larson, Rebecca L. King, Rong He, Wilson Gonsalves, David Inwards, Thomas E. Witzig, Abhisek Swaika, Tania Jain, Nelson Leung, Sikander Ailawadhi, Craig B. Reeder, Martha Q. Lacy, S. Vincent Rajkumar, Shaji Kumar, Robert A. Kyle, Morie A. Gertz, Stephen M. Ansell, Prashant Kapoor
Summary: Waldenstrom macroglobulinemia (WM) is a rare, indolent lymphoma that mostly affects the elderly. A study compared young WM patients to their older counterparts and found that young patients have lower overall survival and higher death attributable to WM. The treatment strategies for WM have not improved the outcome of young patients, and the impact of Bruton tyrosine kinase inhibitors on this patient population is still unknown.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nadine Abdallah, Angela Dispenzieri, Eli Muchtar, Francis K. K. Buadi, Prashant Kapoor, Martha Q. Q. Lacy, Yi L. L. Hwa, Amie Fonder, Miriam A. A. Hobbs, Suzanne R. R. Hayman, Nelson Leung, David Dingli, Ronald S. S. Go, Yi Lin, Wilson I. I. Gonsalves, Moritz Binder, Taxiarchis Kourelis, Rahma Warsame, Robert A. A. Kyle, S. Vincent Rajkumar, Morie A. A. Gertz, Shaji K. K. Kumar
Summary: After long-term follow-up, there is no clear evidence to support the benefit of doxycycline in the post-transplant setting.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Oncology
Bharat Nandakumar, Francis Baffour, Nadine H. H. Abdallah, Shaji K. K. Kumar, Angela Dispenzieri, Francis K. K. Buadi, David Dingli, Martha Q. Q. Lacy, Suzanne R. R. Hayman, Prashant Kapoor, Nelson Leung, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Eli Muchtar, Rahma Warsame, Taxiarchis V. V. Kourelis, Ronald S. S. Go, Robert A. A. Kyle, Morie A. A. Gertz, S. Vincent Rajkumar, Jason Klug, Panagiotis Korfiatis, Wilson I. I. Gonsalves
Summary: Using a deep learning-based segmentation approach, sarcopenia can be accurately detected and measured in clinical computed tomography (CT) images of patients with newly diagnosed multiple myeloma (NDMM). Sarcopenia significantly affects overall survival in NDMM patients and is an independent adverse prognostic factor.
Editorial Material
Oncology
Jean-Sebastien Claveau, David L. Murray, Angela Dispenzieri, Prashant Kapoor, Moritz Binder, Francis Buadi, David Dingli, Amie Fonder, Morie Gertz, Wilson Gonsalves, Suzanne Hayman, Miriam Hobbs, Yi Lisa Hwa, Taxiarchis Kourelis, Martha Lacy, Nelson Leung, Yi Lin, Rahma Warsame, Robert A. Kyle, Vincent Rajkumar, Shaji K. Kumar
Article
Oncology
Nelson Leung, S. Vincent Rajkumar
Summary: Light chain cast nephropathy (LCCN) is a significant cause of acute kidney injury (AKI) in patients with multiple myeloma (MM) and is now considered as a defining event of myeloma. While long-term prognosis has improved, short-term mortality remains higher in patients with LCCN if renal failure is not reversed. Rapid reduction of involved serum free light chain is critical for renal function recovery. Treatment algorithm for MM patients with biopsy-proven LCCN or ruling out other causes of AKI is provided based on randomized trial data whenever available. Clinical trial enrollment is recommended prior to following the treatment algorithm.
BLOOD CANCER JOURNAL
(2023)
Article
Oncology
Alexander J. Ryu, Shaji Kumar, Angela Dispenzieri, Robert A. Kyle, S. Vincent Rajkumar, Thomas C. Kingsley
Summary: This study used machine learning and electronic health record data to identify potential drug candidates for modifying the progression risk of MGUS. Various medications were found to be significantly associated with the risk of MGUS progression, which could inform future prospective studies.
BLOOD CANCER JOURNAL
(2023)
Article
Oncology
Velia Penza, Justin W. Maroun, Rebecca A. Nace, Autumn J. Schulze, Stephen J. Russell
Summary: An improved version of Mengovirus has been developed as a potential treatment for cancer, showing reduced side effects on the nervous system and heart muscle. By modifying the virus's genes, it can stably retain its therapeutic effects and target specific areas without causing harm to the host.
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Pathology
Aldo A. Acosta-Medina, Jithma P. Abeykoon, Ronald S. Go, Gaurav Goyal, Aishwarya Ravindran, Susan M. Schram, Karen L. Rech, Mayo Clin Univ Alabama, Birmingham Histiocytosis Working Grp
Summary: Understanding of histiocytic disorders has been improved by discovering MAPK pathway mutations, especially BRAF(V600E). However, the optimal testing method for BRAF(V600E) is still unknown. This study compared different testing modalities and proposed a framework for evaluating BRAF(V600E) mutation in histiocytic disorders.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yi Lin, Noopur S. Raje, Jesus G. Berdeja, David S. Siegel, Sundar Jagannath, Deepu Madduri, Michaela Liedtke, Jacalyn Rosenblatt, Marcela V. Maus, Monica Massaro, Fabio Petrocca, Ashish Yeri, Olivia Finney, Andrea Caia, Zhihong Yang, Nathan Martin, Timothy B. Campbell, Julie Rytlewski, Jaymes Fuller, Kristen Hege, Nikhil C. Munshi, James N. Kochenderfer
Summary: This study conducted a post hoc analysis of the use of Idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma and found that it is safe and well-tolerated, with a positive impact on response rates. Additionally, the study identified a correlation between the state of T cells and durable responses.
Letter
Oncology
Rahul Banerjee, Bo Wang, Larry D. Anderson, Georgia Mccaughan, Nikita Mehra, Andrew J. Cowan, S. Vincent Rajkumar, Gurbakhash Kaur
BLOOD CANCER JOURNAL
(2023)