Article
Oncology
Luciano J. Costa, Saurabh Chhabra, Eva Medvedova, Bhagirathbhai R. Dholaria, Timothy M. Schmidt, Kelly N. Godby, Rebecca Silbermann, Binod Dhaka, Susan Bal, Smith Gid, Anita D'Souza, Aric Hall, Pamela Hardwick, James Omel, Robert F. Cornell, Parameswaran Had, Natalie S. Callander
Summary: Dara-KRd, AHCT, and MRD response-adapted consolidation lead to a high rate of MRD negativity in NDMM patients. This strategy creates the opportunity of MRD surveillance as an alternative to indefinite maintenance for patients with 0 or 1 HRCA.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Dominik Dytfeld, Tomasz Wrobel, Krzysztof Jamroziak, Tadeusz Kubicki, Pawel Robak, Adam Walter-Croneck, Jaroslaw Czyz, Agata Tyczynska, Agnieszka Druzd-Sitek, Krzysztof Giannopoulos, Adam Nowicki, Tomasz Szczepaniak, Anna Lojko-Dankowska, Magdalena Matuszak, Lidia Gil, Bartosz Pula, Justyna Rybka, Maciej Majcherek, Lidia Usnarska-Zubkiewicz, Lukasz Szukalski, Agnieszka Konska, Jan Maciej Zaucha, Jan Walewski, Damian Mikulski, Olga Czabak, Tadeusz Robak, Oscar B. Lahoud, Jeffrey A. Zonder, Kent Griffith, Andrew Stefka, Ajay Major, Benjamin A. Derman, Andrzej J. Jakubowiak
Summary: This study compared the efficacy and safety of maintenance therapy with carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone in patients with newly diagnosed multiple myeloma. The results showed that the combination therapy group had longer progression-free survival compared to the lenalidomide monotherapy group. Further research is needed to confirm these findings.
Article
Nanoscience & Nanotechnology
Alexandre Detappe, Hung V. -T Nguyen, Yivan Jiang, Michael P. P. Agius, Wencong Wang, Clelia Mathieu, Nang K. K. Su, Samantha L. L. Kristufek, David J. J. Lundberg, Sachin Bhagchandani, Irene M. M. Ghobrial, P. Peter Ghoroghchian, Jeremiah A. A. Johnson
Summary: Nanomedicine platforms offer solutions for cancer therapies by addressing challenges in drug combination due to differing physical properties. The delivery of multiple drugs in nanocarriers outperforms single-drug combinations, providing design principles for improved multiple myeloma therapies.
NATURE NANOTECHNOLOGY
(2023)
Article
Medicine, General & Internal
Pieter Sonneveld, Meletios A. Dimopoulos, Mario Boccadoro, Hang Quach, P. Joy Ho, Meral Beksac, Cyrille Hulin, Elisabetta Antonioli, Xavier Leleu, Silvia Mangiacavalli, Aurore Perrot, Michele Cavo, Angelo Belotti, Annemiek Broijl, Francesca Gay, Roberto Mina, Inger S. Nijhof, Niels W. C. J. van de Donk, Eirini Katodritou, Fredrik Schjesvold, Anna Sureda Balari, Laura Rosinol, Michel Delforge, Wilfried Roeloffzen, Tobias Silzle, Annette Vangsted, Hermann Einsele, Andrew Spencer, Roman Hajek, Artur Jurczyszyn, Sarah Lonergan, Tahamtan Ahmadi, Yanfang Liu, Jianping Wang, Diego Vieyra, Emilie M. J. van Brummelen, Veronique Vanquickelberghe, Anna Sitthi-Amorn, Carla J. de Boer, Robin Carson, Paula Rodriguez-Otero, Joan Blade, Philippe Moreau
Summary: The addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy showed significant improvement in progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Laura Rosinol, Benjamin Hebraud, Albert Oriol, Anne-Laurene Colin, Rafael Rios Tamayo, Cyrille Hulin, Maria Jesus Blanchard, Denis Caillot, Anna Sureda, Miguel Teodoro Hernandez, Bertrand Arnulf, Maria-Victoria Mateos, Margaret Macro, Jesus San-Miguel, Karim Belhadj, Juan Jose Lahuerta, M. Brigid Garelik, Joan Blade, Philippe Moreau
Summary: An integrated analysis of four clinical trials showed that the VRD regimen had superior efficacy and lower incidence of adverse events compared to the VTD regimen in newly diagnosed multiple myeloma patients eligible for transplantation.
FRONTIERS IN ONCOLOGY
(2023)
Article
Medicine, General & Internal
Jesus San-Miguel, Binod Dhakal, Kwee Yong, Andrew Spencer, Sebastien Anguille, Maria-Victoria Mateos, Carlos Fernandez de Larrea, Joaquin Martinez-Lopez, Philippe Moreau, Cyrille Touzeau, Xavier Leleu, Irit Avivi, Michele Cavo, Tadao Ishida, Seok Jin Kim, Wilfried Roeloffzen, Niels W. C. J. van de Donk, Dominik Dytfeld, Surbhi Sidana, Luciano J. Costa, Albert Oriol, Rakesh Popat, Abdullah M. Khan, Yael C. Cohen, P. Joy Ho, James Griffin, Nikoletta Lendvai, Carolina Lonardi, Ana Slaughter, Jordan M. Schecter, Carolyn C. Jackson, Kaitlyn Connors, Katherine Li, Enrique Zudaire, Diana Chen, Jane Gilbert, T. Yeh, Sarah Nagle, Erika Florendo, Lida Pacaud, Nitin Patel, Simon J. Harrison, Hermann Einsele
Summary: In patients with lenalidomide-refractory multiple myeloma, Ciltacabtagene autoleucel (CAR-T cell therapy) showed a lower risk of disease progression or death compared to standard care, highlighting its effectiveness in this patient population.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Health Care Sciences & Services
Christopher Chang-Yew Leow, Michael Sze Yuan Low
Summary: Despite advancements in therapies such as proteasome inhibitors and immunomodulatory drugs, multiple myeloma remains a challenging and relapsing disease with no cure in sight. Over the past decade, novel drugs targeting essential cellular proteins and anti-apoptotic, ribosomal, and nuclear export proteins have emerged as potential treatments against malignant plasma cells.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Hematology
Murielle Roussel, Valerie Lauwers-Cances, Soraya Wuilleme, Karim Belhadj, Salomon Manier, Laurent Garderet, Martine Escoffre-Barbe, Clara Mariette, Lotfi Benboubker, Denis Caillot, Cecile Sonntag, Cyrille Touzeau, Jehan Dupuis, Philippe Moreau, Xavier Leleu, Thierry Facon, Benjamin Hebraud, Jill Corre, Michel Attal
Summary: The study shows that using carfilzomib, lenalidomide, and dexamethasone in combination with transplant treatment for eligible patients with newly diagnosed multiple myeloma can produce rapid and deep responses, with an acceptable safety profile. Close monitoring of cardiovascular adverse events is necessary.
Article
Biotechnology & Applied Microbiology
Li Du, Wei Liu, Flavia Pichiorri, Steven T. Rosen
Summary: This study identified SUMOylation as a potential mechanism regulating lenalidomide resistance in multiple myeloma. Inhibition of SUMOylation can enhance sensitivity to lenalidomide by downregulating IRF4 expression.
CANCER GENE THERAPY
(2023)
Review
Oncology
Felipe de Arriba de la Fuente, Carmen Montes Gaisan, Javier de la Rubia Comos
Summary: Lenalidomide is a key drug for the treatment of multiple myeloma, but excessive use has led to treatment resistance. This review summarizes the current treatment options and discusses potential future therapies. While lenalidomide-based combinations can improve the response rate and survival of multiple myeloma patients, the strategy of using them as a frontline treatment has resulted in early development of resistance. Therefore, there is a need for other treatment options.
Review
Health Care Sciences & Services
Matteo Costacurta, Jackson He, Philip E. Thompson, Jake Shortt
Summary: Thalidomide analogues, or IMiDs, are crucial in treating multiple myeloma by modifying substrate specificity through binding with CRBN. Recent research has advanced our understanding of CRBN's physiological functions, new IMiD derivatives like CELMoDs, and the use of PROTACs to target cancer dependencies. These CRBN-interacting small molecules offer a powerful tool for precision medicine.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Oncology
Vittorio Del Fabro, Mary Ann Di Giorgio, Valerio Leotta, Andrea Duminuco, Claudia Bellofiore, Uros Markovic, Alessandra Romano, Anna Bulla, Angelo Curto Pelle, Federica Elia, Francesco Di Raimondo, Concetta Conticello
Summary: Lenalidomide plus dexamethasone (Len/Dex) is a new standard of care for newly diagnosed multiple myeloma (NDMM) patients who are not eligible for autologous stem cell transplantation. The FIRST trial showed the superiority of continuous therapy with Len/Dex in progression-free survival (PFS) and overall survival (OS). This study evaluates the safety and efficacy of Len/Dex in frail and ultra-frail patients, and correlates it with different variables' impact on PFS and OS.
Article
Medicine, General & Internal
Sultan Qanash, Sameer Alamoudi, Anas Alsuraihi, Asif Jafri, Manar A. Malakah, Bayan Baghlaf, Mulukah Alamoudi, Mohammad M. Althobaiti
Summary: We report a case of multiple myeloma treated with lenalidomide, an immunomodulatory drug. Despite adjusting the dosage due to renal impairment, the patient developed diffuse alveolar hemorrhage (DAH) as a result of lenalidomide use, which has not been previously reported in Saudi Arabia. This case discusses the treatment options for DAH associated with lenalidomide.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Hematology
Ilseyar Akhmetzyanova, Tonya Aaron, Phillip Galbo, Anastasia Tikhonova, Igor Dolgalev, Masato Tanaka, Iannis Aifantis, Deyou Zheng, Xingxing Zang, David Fooksman
Summary: The dissemination and progression of multiple myeloma is associated with an increased inflammatory signature in bone marrow MPs, with CD169(+) MPs playing a critical role in the early spread of myeloma.
Editorial Material
Medicine, General & Internal
Sham Mailankody, Ola Landgren
Summary: BCMA has been recognized as a prognostic marker in multiple myeloma for over two decades, and is now a major target for various treatments including CAR T cells, antibody drug conjugates, and bispecific antibodies. The rapid translation from preclinical studies to FDA-approved treatments demonstrates significant success in the field.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Letter
Hematology
Zuzana Chyra, Tereza Sevikova, Petr Vojta, Janka Puterova, Lucie Brozova, Katerina Growkova, Jana Filipova, Martina Zatopkova, Sebastian Grosicki, Agnieszka Barchnicka, Wieslaw Wiktor-Jedrzejczak, Anna Waszczuk-Gajda, Alexandra Jungova, Aneta Mikulasova, Marian Hajduch, Martin Mokrejs, Ludek Pour, Martin Stork, Lubica Harvanova, Martin Mistrik, Gabor Mikala, Pawel Robak, Anna Czyz, Jakub Debski, Lidia Usnarska-Zubkiewicz, Artur Jurczyszyn, Lukas Stejskal, Gareth Morgan, Fedor Kryukov, Eva Budinska, Michal Simicek, Tomas Jelinek, Matous Hrdinka, Roman Hajek
Article
Hematology
Ceri Bygrave, Charlotte Pawlyn, Faith Davies, Zoe Craig, David Cairns, Anna Hockaday, Matthew Jenner, Gordon Cook, Mark Drayson, Roger Owen, Walter Gregory, Gareth Morgan, Graham Jackson, Martin Kaiser
Summary: Despite equal access to subsequent therapies, myeloma patients who relapse early within 12 months of autologous stem cell transplant have significantly worse progression-free survival and overall survival compared to later relapsing patients, highlighting the urgent need for improved outcome prediction and early intervention strategies.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Graham H. Jackson, Charlotte Pawlyn, David A. Cairns, Alina Striha, Corinne Collett, Anna Waterhouse, John R. Jones, Jamie Wilson, Craig Taylor, Bhuvan Kishore, Mamta Garg, Cathy D. Williams, Kamaraj Karunanithi, Jindriska Lindsay, Matthew W. Jenner, Gordon Cook, Nigel H. Russell, Mark T. Drayson, Martin F. Kaiser, Roger G. Owen, Walter M. Gregory, Faith E. Davies, Gareth J. Morgan
Summary: The Myeloma XI study compared the efficacy of thalidomide and lenalidomide in treating newly diagnosed transplant-ineligible myeloma patients, finding that CRDa had deeper responses for patients aged <= 70 years, but limited tolerability in older, frailer patients.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Oncology
Francesco Maura, Ola Landgren, Gareth J. Morgan
Summary: Advancements in next-generation sequencing technology have allowed for a better understanding of the genetic landscape of multiple myeloma, including drivers and evolutionary processes. This new knowledge can be utilized in clinical settings to improve therapeutic interventions at various disease stages.
CLINICAL CANCER RESEARCH
(2021)
Article
Hematology
Graham H. Jackson, Faith E. Davies, Charlotte Pawlyn, David A. Cairns, Alina Striha, Corinne Collett, Anna Waterhouse, John R. Jones, Bhuvan Kishore, Mamta Garg, Cathy D. Williams, Kamaraj Karunanithi, Jindriska Lindsay, David Allotey, Salim Shafeek, Matthew W. Jenner, Gordon Cook, Nigel H. Russell, Martin F. Kaiser, Mark T. Drayson, Roger G. Owen, Walter M. Gregory, Gareth J. Morgan
Summary: The results of the Myeloma XI phase III trial showed that CRD induction therapy resulted in better progression-free survival and overall survival for multiple myeloma patients, while lenalidomide maintenance therapy improved PFS.
Article
Hematology
Charlotte Pawlyn, David A. Cairns, Tom Menzies, John R. Jones, Matthew W. Jenner, Gordon Cook, Kevin D. Boyd, Mark T. Drayson, Martin F. Kaiser, Roger G. Owen, Walter Gregory, Gareth J. Morgan, Graham H. Jackson, Faith E. Davies
Summary: Autologous stem cell transplant (ASCT) is the standard of care for consolidation after induction therapy in newly diagnosed myeloma patients. While older patients may have a reduced progression-free survival after ASCT, the treatment is well tolerated regardless of age. Data from clinical trials and real-world practice suggest that ASCT can benefit selected older myeloma patients.
Article
Hematology
Kwee L. Yong, Samantha Hinsley, Holger W. Auner, Ceri Bygrave, Martin F. Kaiser, Karthik Ramasamy, Ruth M. de Tute, Debbie Sherratt, Louise Flanagan, Mamta Garg, Stephen Hawkins, Catherine Williams, Jamie Cavenagh, Neil K. Rabin, James Croft, Gareth Morgan, Faith Davies, Roger G. Owen, Sarah R. Brown
Summary: The study compared the efficacy of the proteasome inhibitors carfilzomib and bortezomib in combination with cyclophosphamide and dexamethasone for second-line treatment of myeloma. Carfilzomib showed a higher rate of very good partial response and overall response compared to bortezomib, with carfilzomib maintenance associated with longer progression-free survival.
Review
Oncology
Francesco Maura, Niels Weinhold, Benjamin Diamond, Dickran Kazandjian, Leo Rasche, Gareth Morgan, Ola Landgren
Summary: The identification of mutational processes in multiple myeloma, including a new mutational signature caused by exposure to high-dose melphalan, has been made possible through whole genome and exome sequencing. Exposure to high-dose melphalan increases mutational burden between diagnosis and relapse, with most mutations occurring in heterochromatin and late-replicating regions, rarely affecting key myeloma driver genes.
Review
Cell Biology
Francesco Maura, Eileen M. Boyle, Even H. Rustad, Cody Ashby, David Kaminetzky, Benedetto Bruno, Marc Braunstein, Michael Bauer, Patrick Blaney, Yubao Wang, Hussein Ghamlouch, Louis Williams, James Stoeckle, Faith E. Davies, Brian A. Walker, Kylee Maclachlan, Ben Diamond, Ola Landgren, Gareth J. Morgan
Summary: Analysis of the genetic basis for multiple myeloma has provided important insights into disease initiation, progression, and treatment. Chromothripsis, a type of structural variation, plays a critical role in early disease phases and can be used for clinical classification and predicting high-risk patients.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Benedith Oben, Guy Froyen, Kylee H. Maclachlan, Daniel Leongamornlert, Federico Abascal, Binbin Zheng-Lin, Venkata Yellapantula, Andriy Derkach, Ellen Geerdens, Benjamin T. Diamond, Ingrid Arijs, Brigitte Maes, Kimberly Vanhees, Malin Hultcrantz, Elisabet E. Manasanch, Dickran Kazandjian, Alexander Lesokhin, Ahmet Dogan, Yanming Zhang, Aneta Mikulasova, Brian Walker, Gareth Morgan, Peter J. Campbell, Ola Landgren, Jean-Luc Rummens, Niccolo Bolli, Francesco Maura
Summary: The study demonstrates that MGUS and SMM that do not progress to multiple myeloma have a distinct genomic profile and emerge later in the patient's life.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Kwan Yeung Wong, Gareth J. Morgan, Eileen M. Boyle, Alfred Sze Lok Cheng, Kevin Yuk-Lap Yip, Chor Sang Chim
Summary: Enhancer DNA methylation and MYBPHL expression were studied in multiple myeloma, showing that hypomethylation of CpG1 inside the MYBPHL enhancer was associated with increased MYBPHL expression, potentially implicated in myelomagenesis.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Christie P. M. Verkleij, Marloes E. C. Broekmans, Mark van Duin, Kristine A. Frerichs, Rowan Kuiper, A. Vera de Jonge, Martin Kaiser, Gareth Morgan, Amy Axel, Rengasamy Boominathan, Jocelyn Sendecki, Amy Wong, Raluca Verona, Pieter Sonneveld, Sonja Zweegman, Homer C. Adams, Tuna Mutis, Niels W. C. J. van de Donk
Summary: GPRC5D-targeting T-cell redirecting bispecific antibody talquetamab demonstrates potent anti-myeloma activity, effectively killing MM cells with high GPRC5D expression levels, especially with high effector:target ratio. Combination therapy with daratumumab or pomalidomide enhances talquetamab-mediated lysis of primary MM cells in an additive fashion.
Article
Oncology
Eileen M. Boyle, Louis Williams, Patrick Blaney, Cody Ashby, Michael Bauer, Brian A. Walker, Hussein Ghamlouch, Jinyoung Choi, Emeline Perrial, Yubao Wang, Jessica Caro, James H. Stoeckle, Arnaldo Arbini, David Kaminetzky, Marc Braunstein, Benedetto Bruno, Beatrice Razzo, Benjamin Diamond, Kylee Maclachlan, Francesco Maura, Ola Landgren, Rachel Litke, Christopher D. Fegan, Johnathan Keats, Daniel Auclair, Faith E. Davies, Gareth J. Morgan
Review
Oncology
Jessica Caro, Marc Braunstein, Louis Williams, Benedetto Bruno, David Kaminetzky, Ariel Siegel, Beatrice Razzo, Serge Alfandari, Gareth J. Morgan, Faith E. Davies, Eileen M. Boyle
Summary: Infection and chronic inflammation play significant roles in plasma cell disorders, and are common complications in these conditions. The use of immune-based therapeutic agents in multiple myeloma requires attention to their impact on infection epidemiology and the development of preventive strategies. Furthermore, infection and pathogens are believed to influence disease biology and the formation of plasma cells.
Article
Oncology
Mark A. Dawson, Gautam Borthakur, Brian J. P. Huntly, Anastasios Karadimitris, Adrian Alegre, Aristeidis Chaidos, Dan T. Vogl, Daniel A. Pollyea, Faith E. Davies, Gareth J. Morgan, Jacob L. Glass, Manali Kamdar, Maria -Victoria Mateos, Natalia Tovar, Paul Yeh, Regina Garcia Delgado, Faisal Basheer, Ludovica Marando, Paolo Gallipoli, Anastasia Wyce, Anu Shilpa Krishnatry, Olena Barbash, Evi Bakirtzi, Geraldine Ferron-Brady, Natalie O. Karpinich, Michael T. McCabe, Shawn W. Foley, Thierry Horner, Arindam Dhar, Brandon E. Kremer, Michael Dickinson
Summary: Molibresib, a selective inhibitor of BET proteins, was evaluated as a monotherapy for hematological malignancies. The study consisted of dose escalation to determine the recommended dose and dose expansion to assess safety and efficacy in relapsed/refractory MDS and CTCL patients. Results showed limited antitumor activity and significant toxicities, suggesting the need for combination regimens with molibresib.
CLINICAL CANCER RESEARCH
(2023)