Article
Oncology
Thierry Facon, Gordon Cook, Saad Z. Usmani, Cyrille Hulin, Shaji Kumar, Torben Plesner, Cyrille Touzeau, Nizar J. Bahlis, Supratik Basu, Hareth Nahi, Hartmut Goldschmidt, Hang Quach, Mohamad Mohty, Christopher P. Venner, Katja Weisel, Noopur Raje, Benjamin Hebraud, Karim Belhadj-Merzoug, Lotfi Benboubker, Olivier Decaux, Salomon Manier, Denis Caillot, Jon Ukropec, Huiling Pei, Rian Van Rampelbergh, Clarissa M. Uhlar, Rachel Kobos, Sonja Zweegman
Summary: In patients with transplant-ineligible newly diagnosed multiple myeloma, the combination of daratumumab plus lenalidomide/dexamethasone improved progression-free survival compared to lenalidomide/dexamethasone alone. This benefit was observed regardless of patients' frailty status. Daratumumab showed improved response rates and minimal residual disease negativity across subgroups.
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
Chemistry, Multidisciplinary
Na Yu, Yifan Zhang, Jiaying Li, Wenxing Gu, Shujing Yue, Bin Li, Fenghua Meng, Huanli Sun, Rainer Haag, Jiandong Yuan, Zhiyuan Zhong
Summary: This study reports a novel therapy for depleting multiple myeloma cells with remarkable anti-tumor effects, especially effective against CD38-positive tumor cells, demonstrating safety and efficacy in in vivo experiments.
ADVANCED MATERIALS
(2021)
Article
Hematology
Olivia Perez de Acha, Lauren Reiman, David S. Jayabalan, Zachary J. Walker, Grace Bosma, Alana L. Keller, Sarah E. Parzych, Diana Abbott, Beau M. Idler, Drew Ribadeneyra, Ruben Niesvizky, Peter A. Forsberg, Tomer M. Mark, Daniel W. Sherbenou
Summary: Monoclonal antibodies targeting CD38 are important for the treatment of multiple myeloma, but patients often develop drug resistance. Research shows that waiting 1 year before rechallenging CD38 antibody treatment can achieve temporary efficacy, but this approach may be best used as a bridge to, or after, chimeric antigen receptor T-cell therapy.
Review
Biology
Kazuhito Suzuki, Shingo Yano
Summary: This review discusses the strategies of IMiDs sequencing and IMiD-free interval for lenalidomide-refractory myeloma. It highlights the effectiveness of next-generation IMiDs such as pomalidomide and the potential of using PIs to restore cereblon and overcome lenalidomide resistance. The review also emphasizes the importance of considering safety profiles, social convenience, immunological environment, and genetic alterations in treatment selection.
Article
Oncology
Paul G. Richardson, Shaji K. Kumar, Tamas Masszi, Norbert Grzasko, Nizar J. Bahlis, Markus Hansson, Ludek Pour, Irwindeep Sandhu, Peter Ganly, Bartrum W. Baker, Sharon R. Jackson, Anne-Marie Stoppa, Peter Gimsing, Laurent Garderet, Cyrille Touzeau, Francis K. Buadi, Jacob P. Laubach, Michele Cavo, Mohamed Darif, Richard Labotka, Deborah Berg, Philippe Moreau
Summary: The TOURMALINE-MM1 study showed that ixazomib-Rd had a significant improvement in progression-free survival compared to placebo-Rd in relapsed or refractory multiple myeloma patients, but the difference in median overall survival between the two groups was not statistically significant. Subgroup analysis indicated a greater benefit in overall survival for patients with adverse prognostic factors, and a higher percentage of patients in the ixazomib-Rd group received proteasome inhibitors as next-line therapy compared to the placebo-Rd group.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Hematology
Hilma J. van der Horst, Anne T. Gelderloos, Martine E. D. Chamuleau, Esther C. W. Breij, Sonja Zweegman, Inger S. Nijhof, Marije B. Overdijk, Tuna Mutis
Summary: HexaBody-DRS/DRS antibodies show potential therapeutic efficacy in multiple myeloma, especially exhibiting the highest cytotoxic activity in relapsed/refractory patients who have recently been treated, with synergistic effects observed when combined with other anti-MM drugs such as bortezomib, lenalidomide, and daratumumab.
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
Hematology
Blandine Pouleau, Carole Estoppey, Perrine Suere, Emilie Nallet, Amelie Laurendon, Thierry Monney, Daniela Pais Ferreira, Adam Drake, Laura Carretero-Iglesia, Julie Macoin, Jeremy Berret, Maria Pihlgren, Marie-Agnes Doucey, Girish S. Gudi, Vinu Menon, Venkatesha Udupa, Abhishek Maiti, Gautam Borthakur, Ankita Srivastava, Stanislas Blein, M. Lamine Mbow, Thomas Matthes, Zeynep Kaya, Claire M. Edwards, James R. Edwards, Emmanuelle Menoret, Charlotte Kervoelen, Catherine Pellat-Deceunynck, Philippe Moreau, Eugene Zhukovsky, Mario Perro, Myriam Chimen
Summary: ISB 1342, a bispecific antibody targeting CD38 on tumor cells and CD3 epsilon on T cells, shows promising efficacy in killing daratumumab-resistant multiple myeloma cells. It has demonstrated high cytotoxicity and complete tumor control in preclinical studies, making it a potential option for patients refractory to previous anti-CD38 monoclonal antibody therapies.
Article
Oncology
Thierry Facon, Shaji K. Kumar, Torben Plesner, Robert Z. Orlowski, Philippe Moreau, Nizar Bahlis, Supratik Basu, Hareth Nahi, Cyrille Hulin, Hang Quach, Hartmut Goldschmidt, Michael O'Dwyer, Aurore Perrot, Christopher P. Venner, Katja Weisel, Joseph R. Mace, Noopur Raje, Mourad Tiab, Margaret Macro, Laurent Frenzel, Xavier Leleu, Tahamtan Ahmadi, Jianping Wang, Rian Van Rampelbergh, Clarissa M. Uhlar, Brenda Tromp, Maria Delioukina, Jessica Vermeulen, Saad Z. Usmani
Summary: In patients with newly diagnosed multiple myeloma who are ineligible for stem-cell transplantation, daratumumab plus lenalidomide and dexamethasone significantly improved overall survival and progression-free survival with no new safety concerns.
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.
Article
Oncology
Jacob P. Laubach, Sascha A. Tuchman, Jacalyn M. Rosenblatt, Constantine S. Mitsiades, Kathleen Colson, Kelly Masone, Diane Warren, Robert A. Redd, Dena Grayson, Paul G. Richardson
Summary: The phase 1b study demonstrated the potential of Pano-RVd treatment for relapsed and refractory multiple myeloma, showing promise in overcoming lenalidomide and/or bortezomib resistance.
BLOOD CANCER JOURNAL
(2021)
Review
Oncology
Witold Prejzner, Oliwia Piekos, Karolina Beldzinska, Alicja Sadowska-Klasa, Ewa Zarzycka, Maria Bieniaszewska, Krzysztof Lewandowski, Jan Maciej Zaucha
Summary: This study investigates the role of anti-CD38 antibodies in the treatment of T-ALL and suggests that the combination therapy of daratumumab, venetoclax, and bortezomib may be highly effective and relatively safe for resistant and relapsed T-ALL cases.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Liang Zhou
Summary: This article summarizes the two major molecular mechanisms, antiproliferation and proapoptosis, of drugs used for treating multiple myeloma. It discusses the role of proteasome inhibitors, such as bortezomib, and immunomodulatory drugs, such as lenalidomide, in activating caspase-8 and promoting apoptosis of myeloma cells. The article also explores the regulation of proliferation and apoptosis by caspase-8 in myeloma cells, as well as future directions for caspase-8-based therapy for myeloma.
FRONTIERS IN ONCOLOGY
(2022)
Article
Hematology
Peter A. Forsberg, Adriana C. Rossi, Angelique Boyer, Roger N. Pearse, Karen A. Pekle, David Jayabalan, Stephanie Lakritz, Kari Flicker, Drew Ribadeneyra, Brielle Liotta, Scott Ely, Leora Boussi, John N. Allan, Morton Coleman, Ruben Niesvizky, Tomer M. Mark
Summary: The study evaluated a new treatment regimen for multiple myeloma called Car-BiRd and found that it can achieve similar outcomes with reduced toxicities compared to standard treatment regimens. The results showed a high overall response rate in newly diagnosed MM patients and suggest that the sequential Car-BiRd regimen is an effective and safe approach for upfront treatment.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Hematology
Mark Gurney, Arwen Stikvoort, Emma Nolan, Lucy Kirkham-McCarthy, Stanislav Khoruzhenko, Rama Shivakumar, Sonja Zweegman, Niels W. C. J. Van de Donk, Tuna Mutis, Eva Szegezdi, Subhashis Sarkar, Michael O'Dwyer
Summary: There is strong biological rationale for combining alloeneic natural killer (NK) cell therapies with a chimeric antigen receptor (CAR) to improve the targeting of acute myeloid leukemia (AML). However, CD38 expression on NK cells and its induction during ex vivo NK cell expansion pose challenges to the development of a CD38 CAR-NK cell therapy. This study successfully used gene editing technology to reduce CD38 expression in expanded NK cells, resulting in reduced fratricide and enhanced targeting of primary AML cells. Additionally, pretreatment of AML cells with all-trans retinoic acid further augmented the cytotoxic potential of CD38 CAR-NK cells. These findings support the investigation of CD38 knockdown - CD38 CAR-NK cells as a promising immunotherapeutic approach for AML treatment.
Article
Oncology
Joeri A. J. Douma, Sonja Zweegman, Mieke Alberts, Sandy Kruyswijk, Niels C. W. J. van de Donk, Myra van Linde, Laurien M. Buffart, Henk M. W. Verheul
Summary: Objective smartphone measurements of physical activity and fitness are associated with early trial discontinuation, with high positive predictive values. Optimal cutoff values need to be externally validated in clinical practice.
SUPPORTIVE CARE IN CANCER
(2021)
Article
Cell Biology
Ryosuke Shirasaki, Geoffrey M. Matthews, Sara Gandolfi, Ricardo de Matos Simoes, Dennis L. Buckley, Joseline Raja Vora, Quinlan L. Sievers, Johanna B. Bruggenthies, Olga Dashevsky, Haley Poarch, Huihui Tang, Megan A. Bariteau, Michal Sheffer, Yiguo Hu, Sondra L. Downey-Kopyscinski, Paul J. Hengeveld, Brian J. Glassner, Eugen Dhimolea, Christopher J. Ott, Tinghu Zhang, Nicholas P. Kwiatkowski, Jacob P. Laubach, Robert L. Schlossman, Paul G. Richardson, Aedin C. Culhane, Richard W. J. Groen, Eric S. Fischer, Francisca Vazquez, Aviad Tsherniak, William C. Hahn, Joan Levy, Daniel Auclair, Jonathan D. Licht, Jonathan J. Keats, Lawrence H. Boise, Benjamin L. Ebert, James E. Bradner, Nathanael S. Gray, Constantine S. Mitsiades
Summary: The resistance mechanisms to degraders targeting different oncoproteins are mainly due to prevention, rather than adaptation, of the breakdown of target oncoproteins, which is possibly caused by the loss of function of the cognate E3 ligase or its interactors/regulators.
Article
Oncology
Lisa C. Holthof, Jort J. van der Schans, Afroditi Katsarou, Renee Poels, Anne T. Gelderloos, Esther Drent, Susan E. Van Hal-van Veen, Fengzhi Li, Sonja Zweegman, Niels W. C. J. van de Donk, Maria Themeli, Richard W. J. Groen, Tuna Mutis
Summary: The microenvironment of multiple myeloma can impact therapy outcome, with bone marrow mesenchymal stromal cells protecting MM cells from lysis by certain CAR T cells. BMMSCs did not protect against high-affinity, strongly lytic CAR T cells, but significantly protected against lower affinity, moderately lytic CAR T cells in a cell-cell contact-dependent manner. The study suggests that inhibition of antiapoptotic proteins upregulated in MM cells through BMMSC interactions may improve the outcome of CAR T cell or conventional CTL therapies.
CLINICAL CANCER RESEARCH
(2021)
Article
Hematology
Michele Cavo, Jesus San-Miguel, Saad Z. Usmani, Katja Weisel, Meletios A. Dimopoulos, Herve Avet-Loiseau, Bruno Paiva, Nizar J. Bahlis, Torben Plesner, Vania Hungria, Philippe Moreau, Maria-Victoria Mateos, Aurore Perrot, Shinsuke Iida, Thierry Facon, Shaji Kumar, Niels W. C. J. van de Donk, Pieter Sonneveld, Andrew Spencer, Maria Krevvata, Christoph Heuck, Jianping Wang, Jon Ukropec, Rachel Kobos, Steven Sun, Mia Qi, Nikhil Munshi
Summary: In this study, we explored the impact of minimal residual disease (MRD) on relapsed/refractory multiple myeloma (RRMM) and transplant-ineligible newly diagnosed multiple myeloma (TIE NDMM). The results showed that achieving complete response or better (>= CR) and MRD negativity were associated with improved progression-free survival (PFS) in both RRMM and TIE NDMM patients, regardless of the type of therapy or disease setting.
Review
Hematology
Pellegrino Musto, Monika Engelhardt, Jo Caers, Niccolo' Bolli, Martin Kaiser, Niels van de Donk, Evangelos Terpos, Annemiek Broijl, Carlos Fernandez de Larrea, Francesca Gay, Hartmut Goldschmidt, Roman Hajek, Annette Juul Vangsted, Elena Zamagni, Sonja Zweegman, Michele Cavo, Meletios Dimopoulos, Hermann Einsele, Heinz Ludwig, Giovanni Barosi, Mario Boccadoro, Maria-Victoria Mateos, Pieter Sonneveld, Jesus San Miguel
Summary: Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by specific criteria, with a median time to progression of approximately 5 years. The prognosis and management of SMM patients present challenges due to the potential for rapid transformation into symptomatic disease. While traditional approach involves close observation until progression, recent clinical trials have shown significant benefits for high-risk SMM patients treated with specific medications.
Letter
Hematology
Mesire Aydin, Man Wai Tang, Marielle J. Wondergem, David C. de Leeuw, Jurgen J. Wegman, Bart J. Biemond, Niels W. C. J. van de Donk, Sonja Zweegman, Ellen Meijer, Erfan Nur
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Kristin Roseth Aass, Robin Mjelle, Martin H. Kastnes, Synne S. Tryggestad, Luca M. van den Brink, Ingrid Aass Roseth, Marita Westhrin, Muhammad Zahoor, Siv H. Moen, Tonje M. Vikene Nedal, Glenn Buene, Kristine Misund, Anne-Marit Sponaas, Qianli Ma, Anders Sundan, Richard W. J. Groen, Tobias S. Slordahl, Anders Waage, Therese Standal
Summary: This study demonstrates an unrecognized role of IL-32 in the regulation of plasma cell metabolism. IL-32 interacts with components of the mitochondrial respiratory chain and promotes oxidative phosphorylation. Knocking out IL-32 reduces cell survival and proliferation in myeloma cells, and perturbs metabolic pathways.
Letter
Hematology
Cathelijne Fokkema, Phillipe Moreau, Bronno van der Holt, Jerome Lambert, Mark van Duin, Ruth Wester, Joost L. M. Jongen, Pieter A. van Doorn, Sophie Godet, KonSiong Jie, Olivier Fitoussi, Michel Delforge, Awa Keita-Manta, Odile Luycx, Tom Cupedo, Niels W. C. J. van de Donk, Sonja Zweegman, Jessica T. Vermeulen, Pieter Sonneveld, Annemiek Broijl
Article
Oncology
Mattia D'Agostino, David A. Cairns, Juan Jose Lahuerta, Ruth Wester, Uta Bertsch, Anders Waage, Elena Zamagni, Maria-Victoria Mateos, Daniele Dall'Olio, Niels W. C. J. van de Donk, Graham Jackson, Serena Rocchi, Hans Salwender, Joan Blade Creixenti, Bronno van der Holt, Gastone Castellani, Francesca Bonello, Andrea Capra, Elias K. Mai, Jan Durig, Francesca Gay, Sonja Zweegman, Michele Cavo, Martin F. Kaiser, Hartmut Goldschmidt, Jesus Maria Hernandez Rivas, Alessandra Larocca, Gordon Cook, Jesus F. San-Miguel, Mario Boccadoro, Pieter Sonneveld
Summary: In this study, the Revised International Staging system (R-ISS) for intermediate-risk multiple myeloma patients was revised based on the additive value of each single risk feature.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Maria-Victoria Mateos, Katja Weisel, Valerio De Stefano, Hartmut Goldschmidt, Michel Delforge, Mohamad Mohty, Michele Cavo, Ravi Vij, Joanne Lindsey-Hill, Dominik Dytfeld, Emanuele Angelucci, Aurore Perrot, Reuben Benjamin, Niels W. C. J. van de Donk, Enrique M. Ocio, Christof Scheid, Francesca Gay, Wilfried Roeloffzen, Paula Rodriguez-Otero, Annemiek Broijl, Anna Potamianou, Caline Sakabedoyan, Maria Semerjian, Sofia Keim, Vadim Strulev, Jordan M. Schecter, Martin Vogel, Robert Wapenaar, Tonia Nesheiwat, Jesus San-Miguel, Pieter Sonneveld, Hermann Einsele, Philippe Moreau
Summary: This is the first prospective study for relapsed/refractory multiple myeloma patients, showing a lack of clear standard of care in real-world practice for heavily pretreated patients and resulting in poor outcomes. This supports the need for new treatments with novel mechanisms of action.
Article
Oncology
Adam D. Cohen, Samir Parekh, Bianca D. Santomasso, Jaime Gallego Perez-Larraya, Niels W. C. J. van de Donk, Bertrand Arnulf, Maria-Victoria Mateos, Nikoletta Lendvai, Carolyn C. Jackson, Kevin C. De Braganca, Jordan M. Schecter, Loreta Marquez, Erin Lee, Ingrid Cornax, Enrique Zudaire, Claire Li, Yunsi Olyslager, Deepu Madduri, Helen Varsos, Lida Pacaud, Muhammad Akram, Dong Geng, Andrzej Jakubowiak, Hermann Einsele, Sundar Jagannath
Summary: This study assessed the associated factors for movement and neurocognitive treatment-emergent adverse events (MNTs) in patients with multiple myeloma treated with cilta-cel. Strategies were implemented to monitor and manage patients with MNTs, leading to a significant reduction in the incidence of adverse events.
BLOOD CANCER JOURNAL
(2022)
Letter
Oncology
Mirian Brink, Monique C. Minnema, Otto Visser, Mark-David Levin, Eduardus F. M. Ward Posthuma, Annemiek Broijl, Pieter Sonneveld, Marjolein van der Klift, Wilfried W. H. Roeloffzen, Matthijs Westerman, Cleo R. van Rooijen, Paul A. F. Geerts, Sonja Zweegman, Niels W. C. J. van de Donk, Avinash G. Dinmohamed
BLOOD CANCER JOURNAL
(2022)
Review
Oncology
Sonia Guedan, Maik Luu, Delphine Ammar, Paula Barbao, Chiara Bonini, Philippe Bousso, Christian J. Buchholz, Monica Casucci, Biagio De Angelis, Emmanuel Donnadieu, David Espie, Beatrice Greco, Richard Groen, Johannes B. Huppa, Chahrazade Kantari-Mimoun, Bruno Laugel, Mary Mantock, Janet L. Markman, Emma Morris, Concetta Quintarelli, Michael Rade, Kristin Reiche, Alba Rodriguez-Garcia, Juan Roberto Rodriguez-Madoz, Eliana Ruggiero, Maria Themeli, Michael Hudecek, Ibtissam Marchiq
Summary: Immunotherapy with gene engineered CAR and TCR transgenic T-cells is a groundbreaking treatment in cancer medicine, and has the potential to be used in common solid tumors. However, in order to improve and accelerate the selection of lead T-cell products for clinical translation, it is necessary to assess preclinical models and develop new models with higher predictive value.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Biotechnology & Applied Microbiology
Simone C. Oostindie, Greg A. Lazar, Janine Schuurman, Paul W. H. Parren
Summary: This review discusses the role of avidity in eliciting antibody functional responses and current engineering strategies for manipulating avidity interactions in antibody-based therapies. Avidity, derived from multiple affinity interactions, is fundamental to all aspects of antibody biology and is crucial for enhancing or engineering novel properties in antibody biotherapeutics. Therapeutic antibody mechanisms of action are comprehensively reviewed with an emphasis on engineered optimizations and platforms, leading to a new wave of differentiated antibody drugs with tailored properties and promising improved treatment options for various diseases.
NATURE REVIEWS DRUG DISCOVERY
(2022)