Article
Oncology
Gary Schwartz, Kevin Shee, Bianca Romo, Jonathan Marotti, Alexei Kisselev, Lionel Lewis, Todd Miller
Summary: A single-center phase Ib study showed that the combination of fulvestrant and the proteasome inhibitor ixazomib has a favorable safety profile and antitumor activity in patients with fulvestrant-resistant advanced ER+ breast cancer, warranting further testing.
Article
Oncology
Krina K. Patel, Jatin J. Shah, Lei Feng, Hans C. Lee, Elisabet M. Manasanch, Jasper Olsem, Ashley Morphey, Xiao Jiao Huo, Sheeba K. Thomas, Qaiser Bashir, Muzaffar H. Qazilbash, Donna M. Weber, Robert Z. Orlowski
Summary: This study evaluated the addition of ixazomib to lenalidomide maintenance therapy after autologous stem cell transplantation (ASCT) in patients with multiple myeloma. The study found that the addition of ixazomib resulted in better progression-free survival compared to lenalidomide alone, and was well tolerated by patients.
CLINICAL CANCER RESEARCH
(2022)
Review
Chemistry, Multidisciplinary
Denise Toscani, Luisa Craviotto, Nicola Giuliani
Summary: Bone remodeling changes are typical in multiple myeloma patients, leading to osteolytic lesions. Bone-related events impact quality of life and various treatments have been developed to control bone pain and fractures, although they do not promote bone formation.
APPLIED SCIENCES-BASEL
(2021)
Review
Oncology
Karin Joehrer, Serhat Sezai Cicek
Summary: Multiple myeloma is a common hematological cancer that remains incurable. Plant natural compounds may offer potential therapeutic options for treating this disease.
Article
Pharmacology & Pharmacy
Jaydeep K. Srimani, Paul M. Diderichsen, Michael J. Hanley, Richard Labotka, Neeraj Gupta
Summary: Ixazomib has been approved for maintenance therapy in multiple myeloma patients, with similar progression-free survival benefits seen across different exposure levels. Higher exposures were associated with increased probabilities of maintaining complete response and experiencing certain adverse events, while exposure did not predict hematological adverse events and peripheral neuropathy. Lower apparent clearance values were correlated with a reduced likelihood of escalating the dose to 4 mg. The dose titration approach balanced patient benefit and risk, maximizing the fraction of patients who benefited from the higher dose.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Jaydeep K. Srimani, Paul M. Diderichsen, Michael J. Hanley, Karthik Venkatakrishnan, Richard Labotka, Neeraj Gupta
Summary: This study developed joint population pharmacokinetic/pharmacodynamic models to describe the safety and efficacy of treatment for relapsed/refractory multiple myeloma. The models reliably described the observed safety and efficacy results, providing a simulation tool for prospective trials and potential alternate dosing regimens.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Xu Yang, Amin Liu, Lin Yang, Tiantian Wen, Jia Wang, Jingmiao Shi, Hui Zhou, Zhimeng Chen, Meng Lei, Yongqiang Zhu
Summary: The study investigated the pharmacokinetic profile of FHND6091 as a potential clinical candidate by examining its metabolic stability, metabolite production, metabolic pathways, plasma protein binding, absorption, tissue distribution, excretion, and pharmacokinetics in animals.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
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
Biochemistry & Molecular Biology
Wen Zhang, Xueyuan Wang, Haoyang Zhang, Tiantian Wen, Lin Yang, Hang Miao, Jia Wang, Hailong Liu, Xu Yang, Meng Lei, Yongqiang Zhu
Summary: Novel tripeptide propylene oxide compounds were designed, synthesized and investigated as proteasome inhibitors, showing potential antitumor activities against multiple myeloma cancer cell lines. The compounds demonstrated stability and acceptable biological parameters in in vivo studies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Qingqing Wang, Zhigao Dong, Junnan Su, Jinmei Huang, Pingping Xiao, Lihong Tian, Yongquan Chen, Lili Ma, Xuyan Chen
Summary: Ixazomib inhibits the proliferation of myeloma cells by targeting UBE2K, leading to decreased cell survival and increased apoptosis in a dose-dependent manner. It also affects cell cycle, induces apoptosis, and increases the production of reactive oxygen species.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Letter
Oncology
Seiichi Okabe, Yuko Tanaka, Akihiko Gotoh
Summary: The treatment of multiple myeloma has been improved with the introduction of new drugs, but relapse is still common. Hypoxia plays a crucial role in the bone marrow microenvironment. Inhibitors of PFKFB3 and PFKFB4 show potential in inhibiting myeloma cell growth and enhancing cytotoxicity. Combination treatment with proteasome inhibitors and PFKFB inhibitors has shown enhanced cytotoxic effects.
BIOMARKER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jielin Li, Laura Pohl, Julia Schuler, Nina Korzeniewski, Philipp Reimold, Adam Kaczorowski, Weibin Hou, Stefanie Zschabitz, Cathleen Nientiedt, Dirk Jager, Markus Hohenfellner, Anette Duensing, Stefan Duensing
Summary: This study demonstrates the feasibility of patient-individualized in vitro drug screening and preclinical validation, while highlighting the complexities and limitations of this strategy.
Article
Hematology
Antonio Sacco, Cinzia Federico, Katia Todoerti, Bachisio Ziccheddu, Valentina Palermo, Arianna Giacomini, Cosetta Ravelli, Federica Maccarinelli, Giada Bianchi, Angelo Belotti, Rossella Ribolla, Vanessa Favasuli, Alexey S. Revenko, A. Robert Macleod, Brandon Willis, Hongbo Cai, Joana Hauser, Claire Rooney, Sophie E. Willis, Philip Lloyd Martin, Anna Staniszewska, Helen Ambrose, Lyndsey Hanson, Chiara Cattaneo, Alessandra Tucci, Giuseppe Rossi, Roberto Ronca, Antonino Neri, Stefania Mitola, Niccolo Bolli, Marco Presta, Michele Moschetta, Sarah Ross, Aldo M. Roccaro
Summary: Alterations in KRAS are the most recurring somatic variants in multiple myeloma, and the use of AZD4785 effectively downregulates KRAS and inhibits tumor cell growth, indicating that KRAS is a driver and therapeutic target in multiple myeloma.
Article
Nanoscience & Nanotechnology
Guangtao Gao, Yong Xu, Jingjing Gan, Xinya Cao, Xiaoqing Dong, Mengkun Fang, Ying Du, Peipei Xu, Junyi Che, Bing Chen
Summary: This study reports a targeting strategy for multiple myeloma using platelet membrane-coated nanoparticles encapsulating BTZ. Compared to non-targeted BTZ, the nanoparticle system shows significant improvements in selectivity, cellular uptake, and anticancer effects, demonstrating a high potential for multiple myeloma patients.
Article
Hematology
Yu Abe, Makoto Sasaki, Naoki Takezako, Shigeki Ito, Kazuhito Suzuki, Hiroshi Handa, Takaaki Chou, Takahiro Yoshida, Ikuo Mori, Tomohiro Shinozaki, Kenshi Suzuki
Summary: This study evaluated the efficacy and safety of the oral proteasome inhibitor ixazomib plus lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma. The results showed a 12-month event-free survival rate of 49% and a 12-month progression-free survival rate of 74%. The overall response rate was 73%, with frequent grade ≥3 adverse events being decreased neutrophil and platelet counts.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Meletios A. Dimopoulos, Dominik Dytfeld, Sebastian Grosicki, Philippe Moreau, Naoki Takezako, Mitsuo Hori, Xavier Leleu, Richard LeBlanc, Kenshi Suzuki, Marc S. Raab, Paul G. Richardson, Mihaela Popa McKiver, Ying-Ming Jou, David Yao, Prianka Das, Jesus San-Miguel
Summary: In the phase II ELOQUENT-3 trial, the combination of Elotuzumab, Pomalidomide, and Dexamethasone (EPd) showed significant improvement in progression-free survival (PFS) compared to Pomalidomide and Dexamethasone (Pd) in relapsed/refractory multiple myeloma patients previously treated with Lenalidomide and a proteasome inhibitor. The final overall survival (OS) results revealed that EPd had a statistically significant improvement in OS.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Adam D. Cohen, Maria-Victoria Mateos, Yael C. Cohen, Paula Rodriguez-Otero, Bruno Paiva, Niels W. C. J. van de Donk, Thomas Martin, Attaya Suvannasankha, Kevin C. De Braganca, Christina Corsale, Jordan M. Schecter, Helen Varsos, William Deraedt, Liwei Wang, Martin Vogel, Tito Roccia, Xiaoying Xu, Pankaj Mistry, Enrique Zudaire, Muhammad Akram, Tonia Nesheiwat, Lida Pacaud, Irit Avivi, Jesus San-Miguel
Summary: The CARTITUDE-2 study evaluated the safety and efficacy of cilta-cel in patients with multiple myeloma who had previously received anti-BCMA treatment. The results showed that cilta-cel induced favorable responses in patients who had exhausted other therapies.
Article
Oncology
Fredrik Schjesvold, Bruno Paiva, Vincent Ribrag, Paula Rodriguez-Otero, Jesus F. San-Miguel, Pawel Robak, Markus Hansson, Maika Onishi, Habib Hamidi, Vikram Malhi, Monique Dail, Apurva Javery, Grace Ku, Marc S. Raab
Summary: This phase Ib/II trial evaluated the safety and efficacy of cobimetinib alone and in combination with venetoclax, with or without atezolizumab in patients with relapsed/refractory multiple myeloma. The results showed that cobimetinib alone and in combination with venetoclax, with or without atezolizumab, was safe and tolerable, with moderate anti-tumor activity overall, and higher activity in patients with translocation t(11;14).
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Oncology
Tomas Jelinek, Renata Bezdekova, David Zihala, Tereza Sevcikova, Anjana Anilkumar Sithara, Lenka Pospisilova, Sabina Sevcikova, Petra Polackova, Martin Stork, Zdenka Knechtova, Ondrej Venglar, Veronika Kapustova, Tereza Popkova, Ludmila Muronova, Zuzana Chyra, Matous Hrdinka, Michal Simicek, Juan-Jose Garces, Noemi Puig, Maria-Teresa Cedena, Artur Jurczyszyn, Jorge J. Castillo, Miroslav Penka, Jakub Radocha, Maria Victoria Mateos, Jesus F. San-Miguel, Bruno Paiva, Ludek Pour, Lucie Rihova, Roman Hajek
Summary: This study reveals that >= 2% circulating plasma cells (CTCs) can serve as a biomarker of hidden primary plasma cell leukemia (PCL) and supports the use of flow cytometry to assess CTC levels during the diagnostic workup of multiple myeloma (MM).
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Letter
Oncology
Juan-Jose Garces, Jesus F. San-Miguel, Bruno Paiva
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Jens Hillengass, Tom Martin, Noemi Puig, Bruno Paiva, Saad Usmani, Shaji Kumar, Jesus San-Miguel
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Oncology
Meletios A. Dimopoulos, Albert Oriol, Hareth Nahi, Jesus San-Miguel, Nizar J. Bahlis, Saad Z. Usmani, Neil Rabin, Robert Z. Orlowski, Kenshi Suzuki, Torben Plesner, Sung-Soo Yoon, Dina Ben Yehuda, Paul G. Richardson, Hartmut Goldschmidt, Donna Reece, Tahamtan Ahmadi, Xiang Qin, Wendy Garvin Mayo, Xue Gai, Jodi Carey, Robin Carson, Philippe Moreau
Summary: Based on the analysis of POLLUX, daratumumab in combination with lenalidomide and dexamethasone significantly prolonged progression-free survival in patients with relapsed or refractory multiple myeloma. The final analysis also showed that this combination therapy improved overall survival in these patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Letter
Oncology
Meletios A. Dimopoulos, Jesus San-Miguel
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Gerardo-Javier Marti-Chillon, Sandra Muntion, Silvia Preciado, Lika Osugui, Almudena Navarro-Bailon, Javier Gonzalez-Robledo, Victor Sagredo, Juan F. Blanco, Fermin Sanchez-Guijo
Summary: Despite advancements in ICU patient care, the management of those with SIRS is still a medical challenge. The hyperinflammatory state caused by initial injury and uncontrolled response leads to systemic hypotension and organ failure. MSCs, with their immunomodulatory and regenerative properties, are being explored as a potential therapy for SIRS.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Letter
Hematology
Enrique M. M. Ocio, Sara Bringhen, Joaquin Martinez-Lopez, Jesus San-Miguel, Stefania Oliva, Paula Rodriguez-Otero, Nadia Le Roux, Yvonne Dong, Severine Doroumian, Sandrine Mace, Maria-Victoria Mateos
Article
Oncology
Enrique M. Ocio, Aurore Perrot, Pierre Bories, Jesus F. San-Miguel, Igor W. Blau, Lionel Karlin, Joaquin Martinez-Lopez, Song-Yau Wang, Sara Bringhen, Magda Marcatti, Maria-Victoria Mateos, Paula Rodriguez-Otero, Stefania Oliva, Axel Nogai, Nadia Le Roux, Liyan Dong, Sandrine Mace, Matthieu Gassiot, Thomas Fitzmaurice, Corina Oprea, Philippe Moreau
Summary: This study evaluated the preliminary efficacy, safety, and pharmacokinetics of Isatuximab combined with bortezomib-lenalidomide-dexamethasone in patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation. The results showed a high overall response rate and minimal residual disease negativity, indicating the potential advantages of Isatuximab in this patient population.
Article
Biochemistry & Molecular Biology
Marta Larrayoz, Maria J. Garcia-Barchino, Jon Celay, Amaia Etxebeste, Maddalen Jimenez, Cristina Perez, Raquel Ordonez, Cesar Cobaleda, Cirino Botta, Vicente Fresquet, Sergio Roa, Ibai Goicoechea, Catarina Maia, Miren Lasaga, Marta Chesi, P. Leif Bergsagel, Maria J. Larrayoz, Maria J. Calasanz, Elena Campos-Sanchez, Jorge Martinez-Cano, Carlos Panizo, Paula Rodriguez-Otero, Silvestre Vicent, Giovanna Roncador, Patricia Gonzalez, Satoru Takahashi, Samuel G. Katz, Loren D. Walensky, Shannon M. Ruppert, Elisabeth A. Lasater, Maria Amann, Teresa Lozano, Diana Llopiz, Pablo Sarobe, Juan J. Lasarte, Nuria Planell, David Gomez-Cabrero, Olga Kudryashova, Anna Kurilovich, Maria V. Revuelta, Leandro Cerchietti, Xabier Agirre, Jesus San Miguel, Bruno Paiva, Felipe Prosper, Jose A. Martinez-Climent
Summary: The lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) has hindered therapeutic discoveries. To overcome this limitation, researchers used genetically engineered mice to develop bone marrow tumors that mimic MM pathogenesis. Integrative analyses of mice and patients revealed a common genetic pathway that accelerates disease progression and immune evasion mechanisms that remodel the bone marrow microenvironment differently.
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)
Article
Medicine, General & Internal
Juan F. Blanco, Francisco J. Garcia-Garcia, Eva M. Villaron, Carmen da Casa, Helena Fidalgo, Miriam Lopez-Parra, Jose A. Santos, Fermin Sanchez-Guijo
Summary: This study aimed to evaluate the clinical improvement and safety of mesenchymal stem cells (MSCs) in the treatment of osteonecrosis of the femoral head (ONFH). Eight patients with idiopathic ONFH were included in the study. The injection of autologous bone marrow MSCs improved patients' pain and quality of life, and long-term follow-up results indicated that this treatment was safe and effective.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Hematology
Katja Weisel, Meletios A. Dimopoulos, Jesus San-Miguel, Agne Paner, Monika Engelhardt, Fiona Taylor, Jennifer Lord-Bessen, Christine Yip, Mike Greenwood, Jackson Tang, Michele Cavo
Summary: Triplet regimens with immunomodulatory drugs and proteasome inhibitors have improved outcomes for patients with relapsed/refractory multiple myeloma. In the ELOQUENT-3 trial, the addition of elotuzumab to pomalidomide and dexamethasone did not impact the health-related quality of life (HRQoL) of patients. HRQoL remained stable and there were no significant differences between the treatment arms.