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BACKGROUND Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. METHODS We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. RESULTS A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P=0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy. CONCLUSIONS Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression.
Daratumumab-based treatment for immunoglobulin light-chain amyloidosis / Kastritis E.; Palladini G.; Minnema M.C.; Wechalekar A.D.; Jaccard A.; Lee H.C.; Sanchorawala V.; Gibbs S.; Mollee P.; Venner C.P.; Lu J.; Schonland S.; Gatt M.E.; Suzuki K.; Kim K.; Cibeira M.T.; Beksac M.; Libby E.; Valent J.; Hungria V.; Wong S.W.; Rosenzweig M.; Bumma N.; Huart A.; Dimopoulos M.A.; Bhutani D.; Waxman A.J.; Goodman S.A.; Zonder J.A.; Lam S.; Song K.; Hansen T.; Manier S.; Roeloffzen W.; Jamroziak K.; Kwok F.; Shimazaki C.; Kim J.-S.; Crusoe E.; Ahmadi T.; Tran N.; Qin X.; Vasey S.Y.; Tromp B.; Schecter J.M.; Weiss B.M.; Zhuang S.H.; Vermeulen J.; Merlini G.; Comenzo R.L., Bradley Augustson, Fiona Kwok, Peter Mollee, Simon Gibbs, Chantal Doyen, Greet Bries, Isabelle Vande Broek, Ka Lung Wu, Koen Theunissen, Koen Van Eygen, Michel Delforge, Nathalie Meuleman, Philip Vlummens, Angelo Maiolino, Breno Moreno de Gusmão, Carlos Eduardo Miguel, Edvan Crusoe, Fernanda Moura, Fernanda Seguro, Jandey Bigonha, Juliane Musacchio, Karla Zanella, Laura Garcia, Marcelo Eduardo Zanella Capra, Reijane Alves de Assis, Rosane Bittencourt, Vania Hungria, Walter Braga, Wolney Barreto, Christopher Venner, Donna Reece, Emilie Lemieux-Blanchard, Kevin Song, Michael Sebag, Selay Lam, Victor Zepeda, Haitao Zhang, Jianda Hu, Jin Lu, Juan Li, Songfu Jiang, Ting Niu, Wenming Chen, Xiaonong Chen, Zhen Cai, Zhou Fude, Maja Oelholm Vase, Morten Salomo, Niels Abildgaard, Alain Fuzibet, Anne-Marie Stoppa, Arnaud Jaccard, Bertrand Arnulf, Bruno Moulin, Bruno Royer, David Ghez, Denis Caillot, Dominique Chauveau, Franck Bridoux, Lauriane Clement-Filliatre, Lionel Karlin, Lotfi Benboubker, Mamoun Dib, Margaret Macro, Mohamad Mohty, Olivier Decaux, Olivier Hermine, Olivier Tournilhac, Philippe Moreau, Salomon Manier, Sylvain Choquet, Véronique Dorvaux, Alexander Carpinteiro, Axel Nogai, Britta Besemer, Christoph Roellig, Roland Fenk, Stefan Knop, Stefan Schönland, Timon Hansen, Argiris Symeonidis, Efstathios Kastritis, Gabor Mikala, Tamás Masszi, Zsolt Nagy, Celia Suriu, Hila Magen, Iuliana Vaxman, Lev Shvidel, Meir Preis, Moshe Gatt, Noa Lavi, Osnat Jarchowsky, Tamar Tadmor, Yael Cohen, Angelo Vacca, Giovanni Palladini, Mario Boccadoro, Maurizio Martelli, Maurizio Musso, Michele Cavo, Chihiro Shimazaki, Hiroyuki Takamatsu, Kazutaka Sunami, Kenshi Suzuki, Nagaaki Katoh, Shinsuke Iida, Takayuki Ikezoe, Tomoaki Fujisaki, Yuta Katayama, Chang Ki Min, Ho-Jin Shin, Jin Seok Kim, Jung Yong Hong, Ki Hyun Kim, Sung-Soo Yoon, Aline Ramirez, Alvaro Cabrera, Christian Ramos, David Gomez Almaguer, Deborah Martinez, Guillermo Ruiz, Helen Dayani Caballero, Juan Antonio Flores Jimenez, Annemiek Broijl, Laurens Nieuwenhuizen, Monique Minnema, Paula Ypma, Wilfried Roeloffzen, Dominik Dytfeld, Grzegorz Charlinski, Grzegorz Helbig, Krzysztof Jamroziak, Sebastian Grosicki, Wieslaw Jedrzejczak, Albert Oriol Rocafiguera, Elham Askari, Fernando Escalante Barrigon, Isabel Krsnik Castello, Javier De la Rubia Comos, Jesus Martin Sanchez, Joaquin Martinez Lopez, Jose Angel Hernandez Rivas, Luis Felipe Casado Montero, Maria Jesus Blanchard Rodriguez, Maria Teresa Cibeira Lopez, Maria Victoria Mateos Manteca, Marta Sonia Gonzalez Perez, Mercedes Gironella Mesa, Rafael Rios Tamayo, Ramon Lecumberri Villamediana, Ricarda Garcia Sanchez, Sunil Lakhwani, Yolanda Gonzalez, Hareth Nahi, Kristina Carlsson, Markus Hansson, Ulf-Henrik Mellqvist, Ali Unal, Burhan Ferhanoglu, Hayri Ozsan, Levent Undar, Mehmet Turgut, Mehmet Yilmaz, Meral Beksac, Muhlis Cem Ar, Muzaffer Demir, Sevgi Besisik, Ashutosh Wechalekar, Jamie Cavenagh, Jim Cavet, Mark Cook, Rachel Hall, Adam Waxman, Anuj Mahindra, Cesar Rodriguez Valdes, Christine Ye, Craig Reeder, Daphne Friedman, David Siegel, Divaya Bhutani, Edward Libby, Eva Medvedova, Frank Passero, Giada Bianchi, Giampaolo Talamo, Guido Tricot, Hans Lee, Heather Landau, Jan Moreb, Jason Valent, Jeffrey Matous, Jeffrey A Zonder, Jesus Berdeja, Jonathan Kaufman, Keith Stockerl-Goldstein, Keren Osman, Ketan Doshi, Kevin Barton, Larry Anderson, Manisha Bhutani, Mehmet Kocoglu, Michael Rosenzweig, Michael Schuster, Michaela Liedtke, Morie Gertz, Naresh Bumma, Natalie Callander, Raymond Comenzo, Robert Vescio, Roger Pearse, Sandy W Wong, Stacey A Goodman, Stefano Tarantolo, Taimur Sher, Tibor Kovacsovics, Tomer Mark, Vaishali Sanchorawala, William Bensinger. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - STAMPA. - 385:1(2021), pp. https://www.nejm.org/doi/10.1056/NEJMoa2028631?.46-https://www.nejm.org/doi/10.1056/NEJMoa2028631?.58. [10.1056/NEJMoa2028631]
Daratumumab-based treatment for immunoglobulin light-chain amyloidosis
BACKGROUND Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. METHODS We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. RESULTS A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P=0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy. CONCLUSIONS Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/865219
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.
