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1. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study

Author

Abulafia, Adi Shacham, Al-Ali, Haifa Kathrin, Andreasson, Bjorn, Angona, Anna, Ayala, Rosa, Bang, Soo-Mee, Bank, Bruce, Barraco, Fiorenza, Beggiato, Eloise, Benghiat, Fleur Samantha, Bonifacio, MassimiliaNo, Bories, Claire, Borsaru, Gabriela, Brabrand, Mette, Braester, Andrei, Broliden, Andes, Buxhofer-Ausch, Veronika, Cambier, Nathalie, Caramella, Marianna, Carpentier, Benjamin, Cascavilla, Nicola, Castellano, Maria Giraldo, Chang, Hung, Chen, Chih-Cheng, Cheong, June-Won, Choi, Yunsuk, Choi, Philip, Corsetti, Maria Teresa, Cuadrado, Isabel Montero, Cunningham, Julia, Damaj, Gandhi Laurent, De Stefano, Valerio, Delage, Robert, Delgado, Regina Garcĺa, Diaz, Jose Miguel Torregrosa, Dombi, Péter, Dubruille, Viviane, Egyed, Miklós, El Fassi, Daniel, Elinder-Camburn, Anna, Elli, Elena Maria, Ellis, Martin, Fava, Carmen, Fazal, Salman, Fleischman, Angela, Foltz, Lynda, Fox, Laura, Gabrail, Nashat, Garcĺa-Gutiérrez, Jose Valentĺn, Gerds, Aaron, Girault, Stephane, Gisslinger, Heinz, Gluvacov, Alexandru, Goh, Yeow Tee, Göthert, Joachim, Granacher, Nikki, Grosicki, Sebastian, Gupta, Vikas, Hadjiev (Hadzhiev), Evgeni (Evgueniy), Hafraoui, Kaoutar, Hamed, Aryan, Harrison, Claire, Hasselbalch, Hans, Hauser, Hanns, Heaney, Mark, Hebart, Holger, Hernandez Rivas, Jesus Maria, Higuero Saavedra, Victor, Hillis, Christopher, Hou, Hsin-An, How, Jonathan, Huang, Daniel, Hus, Marek, Illés, Arpad, Isidori, Alessandro, Iurlo, Alessandra, Ivanov, Vadim, Johansson, Peter, Jung, Chul Won, Kiladjian, Jean-Jacques, Kirgner, Ilya, Koren-Michowitz, Maya, Koschmieder, Steffen, Kosztolanyi, Szabolcs Ors, Kreiniz, Natalia, Kuykendall, Andrew, Lambert, Jonathan, Laribi, Kamel, Lascaux, Axelle, Lavie, Noa, Lavie, David, Lazaroiu, Mihaela, Leahy, Michael, Lech-Maranda, Ewa, Lee, Sung-Eun, Lee, Won Sik, Legrand, Ollivier, Lemoli, Roberto, Liang, James, Lim, Sung-Nam, Loschi, Michael, Lucchesi, Alessandro, Macarie, Ioan, Marolleau, Jean-Pierre, Martelli, Maurizio, Mayer, Jiri, McCloskey, James, McDermott, Christopher, McLornan, Donal, McMahon, Brandon, Mehta, Priyanka, Mesa, Ruben, Mikala, Gábor, Milojkovic, Dragana, Mineur, Philippe, Mishchenko, Elena, Moon, Joon Ho, Nagy, Zsolt, Narayanan, Srinivasan, O'Connell, Casey, Ocroteala, Luminita, Oh, Stephen, Ojeda-Uribe, Mario, Ong, Kiat Hoe, Otegbeye, Folashade, Palmer, Jeanne, Pane, Fabrizio, Passamonti, Francesco, Patriarca, Andrea, Perkins, Andrew, Pietrantuono, Giuseppe, Plander, Mark, Platzbecker, Uwe, Prasad, Ritam, Prejzner, Witold, Rachow, Tobias, Radinoff, Atanas, Rejtő, László, Rinaldi, Ciro, Robak, Tadeusz, Rodriguez, Maria Angeles Fernandez, Ronson, Aaron, Ross, David, Sacha, Tomasz, Sadjadian, Parvis, Salar, Antonio, Santillana, Guillermo Sanz, Scheid, Christof, Schmidt, Aline, Severinsen, Marianne Tang, Stoeva, Vera, Szwedyk, Paweł, Tiribelli, Mario, Trautmann-Grill, Karolin, Trottier, Amy, Tzvetkov, Nikolay, van Droogenbroeck, Janusz, Vannucchi, Alessandro, Verstovsek, Srdan, Vianelli, Nicola, von Bubnoff, Nikolas, Wolf, Dominik, Woszczyk, Dariusz, Woźny, Tomasz, Wróbel, Tomasz, Xicoy, Blanca, Yeh, Su-Peng, Yoon, Sung-Soo, Gerds, Aaron T, Vannucchi, Alessandro M, Kuykendall, Andrew T, Lazaroiu, Mihaela C, Egyed, Miklos, Fox, Maria Laura, Harrison, Claire N, Klencke, Barbara J, Ro, Sunhee, Donahue, Rafe, and Kawashima, Jun

Published
2023
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2. Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a double-blind, randomised, phase 3 trial

Author

Lee, Jong Wook, primary, Griffin, Morag, additional, Kim, Jin Seok, additional, Lee Lee, Lily Wong, additional, Piatek, Caroline, additional, Nishimura, Jun-ichi, additional, Carrillo Infante, Cynthia, additional, Jain, Deepak, additional, Liu, Peng, additional, Filippov, Gleb, additional, Sicre de Fontbrune, Flore, additional, Risitano, Antonio, additional, Kulasekararaj, Austin G, additional, Barcellini, Wilma, additional, Barraco, Fiorenza, additional, Beneitez Pastor, David, additional, Capra, Marcelo, additional, Chew, Lee Ping, additional, Chrysavgi, Lalayanni, additional, De Castro, Carlos, additional, de la Tour, Régis Peffault, additional, De Oliveira, Michel Michels, additional, Di Bona, Eros, additional, Forcade, Edouard, additional, Fu, Chieh-Lin, additional, Furha, Cossor, additional, Gaya Valls, Anna, additional, Giannouli, Stavroula, additional, Gonzalez-Fernandez, Ataulfo, additional, Gural, Alexander, additional, Gutierrez, Emilio Ojeda, additional, Hernández-Rodríguez, Inés, additional, Ibrahim, Ibrahim, additional, Iori, Anna Paola, additional, Ishida, Tadao, additional, Jang, Jun Ho, additional, Kim, Jeong-A, additional, Kitano, Toshiyuki, additional, Kosugi, Hiroshi, additional, Kreiniz, Natalia, additional, Kulasekararaj, Austin, additional, Lee, Jong Wook, additional, Mayer, Jiri, additional, Mitchell, Lindsay, additional, Mori, Yasuo, additional, Nishiwaki, Kaichi, additional, Notaro, Rosario, additional, Nunez, Ramiro, additional, Obara, Naoshi, additional, Oliva, Esther Natalie, additional, Patriquin, Christopher, additional, Pessoa, Viviani, additional, Piekarska, Agnieszka, additional, Raza, Shahzad, additional, Risitano, Antonio Maria, additional, Rojnuckarin, Ponlapat, additional, Samuel, Desmond, additional, Shammo, Jamile, additional, Tadmor, Tamar, additional, Takami, Akiyoshi, additional, Tamari, Roni, additional, Terriou, Louis, additional, Uchiyama, Hitoji, additional, Vannucchi, Alessandro Maria, additional, and Yamaguchi, Hiroki, additional

Published
2023
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4. The Involvement of LAG-3 positive Plasma Cells in the Development of Multiple Myeloma.

Author

Kreiniz, Natalia, Eiza, Nasren, Tadmor, Tamar, Levy Yurkovski, Ilana, Matarasso Greenfeld, Sarah, Sabag, Adi, Mubariki, Raeda, Suriu, Celia, Votinov, Ekaterina, Toubi, Elias, and Vadasz, Zahava

Subjects
*MULTIPLE myeloma, *PLASMA cells, *PROTEIN expression, *PRECANCEROUS conditions, *FLOW cytometry
Abstract

The Lymphocyte-Activation Protein 3 (LAG-3) inhibitory receptor is expressed on regulatory plasma cells (PCs). Micro-environmental cells that express LAG-3 were found to be increased during the progression of smoldering multiple myeloma (SMM). To assess the possible role of LAG-3 expression on regulatory PCs in patients with plasma cell dyscrasia. Purified Cluster of Differentiation 138 (CD138+) PCs from patients with premalignant conditions, active multiple myeloma (MM), and controls were analyzed for the expression of LAG-3 by flow cytometry. Autologous CD8+T cells were incubated with sorted LAG-3pos or LAG-3neg PCs for 24 h. The expression of granzyme (Grz) in CD8+T cells was assessed by flow cytometry. LAG-3 expression on PCs in active MM (newly diagnosed and relapse refractory MM) was significantly increased compared to monoclonal gammopathy of undetermined significance (MGUS)/ SMM. Grz expression was significantly decreased in CD8+T cells incubated with CD138+LAG-3pos PCs, compared to CD138+LAG-3neg PCs in patients with plasma cell dyscrasia, n = 31, p = 0.0041. LAG-3 expression on malignant PCs can be involved in the development of MM from MGUS by decreasing the expression of Grz in CD8+T cells. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study

Author

Verstovsek, Srdan, primary, Gerds, Aaron T, additional, Vannucchi, Alessandro M, additional, Al-Ali, Haifa Kathrin, additional, Lavie, David, additional, Kuykendall, Andrew T, additional, Grosicki, Sebastian, additional, Iurlo, Alessandra, additional, Goh, Yeow Tee, additional, Lazaroiu, Mihaela C, additional, Egyed, Miklos, additional, Fox, Maria Laura, additional, McLornan, Donal, additional, Perkins, Andrew, additional, Yoon, Sung-Soo, additional, Gupta, Vikas, additional, Kiladjian, Jean-Jacques, additional, Granacher, Nikki, additional, Lee, Sung-Eun, additional, Ocroteala, Luminita, additional, Passamonti, Francesco, additional, Harrison, Claire N, additional, Klencke, Barbara J, additional, Ro, Sunhee, additional, Donahue, Rafe, additional, Kawashima, Jun, additional, Mesa, Ruben, additional, Abulafia, Adi Shacham, additional, Andreasson, Bjorn, additional, Angona, Anna, additional, Ayala, Rosa, additional, Bang, Soo-Mee, additional, Bank, Bruce, additional, Barraco, Fiorenza, additional, Beggiato, Eloise, additional, Benghiat, Fleur Samantha, additional, Bonifacio, MassimiliaNo, additional, Bories, Claire, additional, Borsaru, Gabriela, additional, Brabrand, Mette, additional, Braester, Andrei, additional, Broliden, Andes, additional, Buxhofer-Ausch, Veronika, additional, Cambier, Nathalie, additional, Caramella, Marianna, additional, Carpentier, Benjamin, additional, Cascavilla, Nicola, additional, Castellano, Maria Giraldo, additional, Chang, Hung, additional, Chen, Chih-Cheng, additional, Cheong, June-Won, additional, Choi, Yunsuk, additional, Choi, Philip, additional, Corsetti, Maria Teresa, additional, Cuadrado, Isabel Montero, additional, Cunningham, Julia, additional, Damaj, Gandhi Laurent, additional, De Stefano, Valerio, additional, Delage, Robert, additional, Delgado, Regina Garcĺa, additional, Diaz, Jose Miguel Torregrosa, additional, Dombi, Péter, additional, Dubruille, Viviane, additional, Egyed, Miklós, additional, El Fassi, Daniel, additional, Elinder-Camburn, Anna, additional, Elli, Elena Maria, additional, Ellis, Martin, additional, Fava, Carmen, additional, Fazal, Salman, additional, Fleischman, Angela, additional, Foltz, Lynda, additional, Fox, Laura, additional, Gabrail, Nashat, additional, Garcĺa-Gutiérrez, Jose Valentĺn, additional, Gerds, Aaron, additional, Girault, Stephane, additional, Gisslinger, Heinz, additional, Gluvacov, Alexandru, additional, Göthert, Joachim, additional, Hadjiev (Hadzhiev), Evgeni (Evgueniy), additional, Hafraoui, Kaoutar, additional, Hamed, Aryan, additional, Harrison, Claire, additional, Hasselbalch, Hans, additional, Hauser, Hanns, additional, Heaney, Mark, additional, Hebart, Holger, additional, Hernandez Rivas, Jesus Maria, additional, Higuero Saavedra, Victor, additional, Hillis, Christopher, additional, Hou, Hsin-An, additional, How, Jonathan, additional, Huang, Daniel, additional, Hus, Marek, additional, Illés, Arpad, additional, Isidori, Alessandro, additional, Ivanov, Vadim, additional, Johansson, Peter, additional, Jung, Chul Won, additional, Kirgner, Ilya, additional, Koren-Michowitz, Maya, additional, Koschmieder, Steffen, additional, Kosztolanyi, Szabolcs Ors, additional, Kreiniz, Natalia, additional, Kuykendall, Andrew, additional, Lambert, Jonathan, additional, Laribi, Kamel, additional, Lascaux, Axelle, additional, Lavie, Noa, additional, Lazaroiu, Mihaela, additional, Leahy, Michael, additional, Lech-Maranda, Ewa, additional, Lee, Won Sik, additional, Legrand, Ollivier, additional, Lemoli, Roberto, additional, Liang, James, additional, Lim, Sung-Nam, additional, Loschi, Michael, additional, Lucchesi, Alessandro, additional, Macarie, Ioan, additional, Marolleau, Jean-Pierre, additional, Martelli, Maurizio, additional, Mayer, Jiri, additional, McCloskey, James, additional, McDermott, Christopher, additional, McMahon, Brandon, additional, Mehta, Priyanka, additional, Mikala, Gábor, additional, Milojkovic, Dragana, additional, Mineur, Philippe, additional, Mishchenko, Elena, additional, Moon, Joon Ho, additional, Nagy, Zsolt, additional, Narayanan, Srinivasan, additional, O'Connell, Casey, additional, Oh, Stephen, additional, Ojeda-Uribe, Mario, additional, Ong, Kiat Hoe, additional, Otegbeye, Folashade, additional, Palmer, Jeanne, additional, Pane, Fabrizio, additional, Patriarca, Andrea, additional, Pietrantuono, Giuseppe, additional, Plander, Mark, additional, Platzbecker, Uwe, additional, Prasad, Ritam, additional, Prejzner, Witold, additional, Rachow, Tobias, additional, Radinoff, Atanas, additional, Rejtő, László, additional, Rinaldi, Ciro, additional, Robak, Tadeusz, additional, Rodriguez, Maria Angeles Fernandez, additional, Ronson, Aaron, additional, Ross, David, additional, Sacha, Tomasz, additional, Sadjadian, Parvis, additional, Salar, Antonio, additional, Santillana, Guillermo Sanz, additional, Scheid, Christof, additional, Schmidt, Aline, additional, Severinsen, Marianne Tang, additional, Stoeva, Vera, additional, Szwedyk, Paweł, additional, Tiribelli, Mario, additional, Trautmann-Grill, Karolin, additional, Trottier, Amy, additional, Tzvetkov, Nikolay, additional, van Droogenbroeck, Janusz, additional, Vannucchi, Alessandro, additional, Verstovsek, Srdan, additional, Vianelli, Nicola, additional, von Bubnoff, Nikolas, additional, Wolf, Dominik, additional, Woszczyk, Dariusz, additional, Woźny, Tomasz, additional, Wróbel, Tomasz, additional, Xicoy, Blanca, additional, and Yeh, Su-Peng, additional

Published
2023
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9. The Involvement of LAG3+ Plasma Cells in the Development of Multiple Myeloma

Author

Kreiniz, Natalia, primary, Eiza, Nasreen, additional, Tadmor, Tamar, additional, Sabag, Adi, additional, Matarasso Greenfeld, Sarah, additional, Levy, Ilana, additional, Surio, Celia, additional, Votinov, Ekaterina, additional, Mubariki, Raeda, additional, Polliack, Aaron, additional, Toubi, Elias, additional, and Vadasz, Zahava, additional

Published
2022
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11. Bortezomib Maintenance Therapy as a Standard of Care Provides Favorable Outcomes in Newly Diagnosed Myeloma Patients: A Multisite Real-Life Study

Author

Moshe E. Gatt, Efrat Luttwak, Svetlana Trestman, Irit Avivi, Tamar Tadmor, Kreiniz Natalia, Noam Benyamini, Eyal Lebel, Noa Lavi, Celia Suriu, Moshe Mittelman, Netanel A. Horowitz, Ory Rouvio, Yael C Cohen, and Mika Geva

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Subgroup analysis, Ixazomib, Bortezomib, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Maintenance therapy, Internal medicine, medicine, Autologous transplantation, Humans, Adverse effect, Multiple myeloma, Lenalidomide, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Hematology, Middle Aged, medicine.disease, Treatment Outcome, Oncology, chemistry, 030220 oncology & carcinogenesis, Female, business, Multiple Myeloma, 030215 immunology, medicine.drug
Abstract

Background Lenalidomide and ixazomib maintenance improve long-term outcomes in newly diagnosed multiple myeloma (NDMM) patients. However, there is less evidence to support bortezomib (BTZ) maintenance therapy, and real-life data on maintenance are scarce. We investigated the efficacy and safety of BTZ maintenance therapy in NDMM. Patients and Methods A retrospective multisite study was performed in 6 medical centers in Israel. All consecutive patients with NDMM diagnosed between January 1, 2010, and July 3, 2019, who received a BTZ-based induction, with or without an autologous transplantation, followed by BTZ maintenance therapy, were identified. Maintenance therapy was defined as BTZ (1.3 mg/m2) once every 2 weeks, administered subcutaneously alone or with dexamethasone, or weekly BTZ monotherapy. Results A total of 105 patients were identified, 58 of whom had received a transplant (transplant eligible) and 47 who had not (not transplant eligible). During BTZ maintenance therapy, 96% had one or more adverse event, 11.5% had grade 3 or higher adverse events, and 11.5% discontinued treatment due to toxicity. Median progression-free survival (PFS) and overall survival were 45 and 91.5 months, respectively; 4-year survival was 88%. Adverse cytogenetics was associated with worse PFS (24 vs. 46 months, P = .001). In subgroup analysis, adverse cytogenetics were associated with worse PFS (P Conclusion Analysis of multisite real-life data showed that BTZ maintenance therapy is safe, well tolerated, and effective. Median PFS was similar to that reported with alternative maintenance strategies. Our findings further support its use among patients with adverse cytogenetics, it may also be relevant for patients with lenalidomide-intolerant disease.

Published
2020

14. Outcomes of Post-Induction Bortezomib Therapy in Patients with Newly diagnosed Multiple Myeloma: A Multi-Center Retrospective Observational Study

Author

Luttwak, Efrat, primary, Gatt, Moshe, additional, Lavi, Noa, additional, Tadmor, Tamar, additional, Kreiniz, Natalia, additional, Benyamini, Noam, additional, Horowitz, Netanel, additional, Suriu, Celia, additional, Avivi, Irit, additional, Trestman, Svetlana, additional, Mittelman, Moshe, additional, Ram, Ron, additional, Rouvio, Ory, additional, and Cohen, Yael, additional

Published
2019
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16. Time to Progression Post-Induction Predicts Outcomes of Ixazomib Based Therapy for Relapsed/Refractory Myeloma: Real World Data from a Multi-Site Israeli Registry Study

Author

Cohen, Yael C, primary, Magen, Hila, additional, Lavi, Noa, additional, Gatt, Moshe E., additional, Chubar, Evgeni, additional, Kreiniz, Natalia, additional, Tadmor, Tamar, additional, Trestman, Svetlana, additional, Vitkon, Roy, additional, Rouvio, Ory, additional, Shvetz, Olga, additional, Shaulov, Adir, additional, and Avivi, Irit, additional

Published
2018
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18. Demyelinating brain lesions developing in a patient with chronic lymphocytic leukemia shortly after treatment with a fludarabine containing regimen.

Author

Kreiniz, Natalia, Garty‐Ofir, Maya, Bejar, Jacob, Polliack, Aaron, and Tadmor, Tamar

Subjects
CHRONIC lymphocytic leukemia, BRAIN damage, FLUDARABINE, PARIETAL lobe, FRONTAL lobe, THROMBOTIC thrombocytopenic purpura, FRONTAL lobe diseases
Abstract

Autoimmune manifestations are known to occur in patients with chronic lymphocytic leukemia (CLL) and of these hemolytic anemia and immune thrombocytopenia are the most well recognized. Autoimmunity may also be triggered by some of the therapeutic agents used like purine analoges and these events may sometimes be severe and even fatal. Non‐hematological autoimmune stigmata occur far less frequently and are rarely encountered. Here we report a 59 year‐old‐woman, with CLL, who complained of recurrent headache starting 1 month after completing 6 cycles of fludarabine, cyclophosphamide, and rituximab combination therapy. Computed tomography scan of the brain showed a contrast enhancing lesion of 1 cm in diameter, with surrounding edema in the right frontal lobe. Brain MRI revealed ring enhancing lesions in the right frontal lobe and some additional small lesions in the left parietal lobe. Brain biopsy showed an inflammatory demyelinating lesion, not associated with JC virus. The patient subsequently improved after steroid therapy. Currently, after 2 years of follow‐up, she remains in complete hematologic remission, has no neurological deficits, and is carefully followed by a team of neurologists and hematologists. Treating physicians should be aware of this rare autoimmune inflammatory demyelinating lesion which can occur in patients with CLL during the course of treatment and that may be linked to treatment with purine analogues like fludarabine. [ABSTRACT FROM AUTHOR]

Published
2021
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19. Treatment and prognosis of stage I follicular lymphoma in the modern era – does PET matter?

Author

Bentur, Ohad S., primary, Gurion, Ronit, additional, Gafter-Gvili, Anat, additional, Gatt, Moshe, additional, Shvidel, Lev, additional, Horowitz, Netanel A., additional, Ram, Ron, additional, Herishanu, Yair, additional, Sarid, Nadav, additional, Paltiel, Ora, additional, Ganzel, Chezi, additional, Kreiniz, Natalia, additional, Dally, Najib, additional, Gutwein, Odit, additional, Raanani, Pia, additional, Avivi, Irit, additional, and Perry, Chava, additional

Published
2017
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21. A Prospective, Phase-II Study to Evaluate the Efficacy and Safety of Obinutuzumab, Ibrutinib, and Venetoclax (GIVeRS) in Patients with Richter's Syndrome

Author

Tadmor, Tamar, Benjamini, Ohad, Goldschmidt, Neta, Kreiniz, Natalia, Bairey, Osnat, Harel, Reut, Inbar, Tsofia, Wolach, Ofir, and Herishanu, Yair

Abstract

Background: Richter's syndrome (RS) is an aggressive histologic transformation of chronic lymphocytic leukemia (CLL), most commonly to diffuse large B-cell lymphoma (DLBCL). RS is characterized by a rapid clinical course, low responses to therapy, and poor long-term survival. Chemoimmunothreapy for RS achieves overall response rates of 40% to 60%, and median progression-free survival (PFS) and overall survival (OS) of 3 to 10 months and 6 to 21 months, respectively. More recently, single targeted agents of either ibrutinib or venetocolax have been shown some clinical activity in RS. Furthermore, ibrutinib combined with venetoclax with or without anti-CD20 antibodies has a synergistic activity in CLL, resulting in deep and prolong responses along with a good safety profile.

Published
2023
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22. Treatment and prognosis of stage I follicular lymphoma in the modern era - does PET matter?

Author

Bentur, Ohad S., Sarid, Nadav, Ram, Ron, Herishanu, Yair, Avivi, Irit, Perry, Chava, Kreiniz, Natalia, Dally, Najib, Gurion, Ronit, Raanani, Pia, Gafter-Gvili, Anat, Gutwein, Odit, Gatt, Moshe, Paltiel, Ora, Shvidel, Lev, Ganzel, Chezi, and Horowitz, Netanel A.

Subjects
LYMPHOMAS, HODGKIN'S disease, RADIOTHERAPY, TOMOGRAPHY, PROGRESSION-free survival
Abstract

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. Patients with stage I disease are usually treated with radiotherapy (RT). In previous studies, mostly from the pre positron emission tomography-computed tomography (PET-CT) era, the 5 year progression-free survival (PFS) and overall survival (OS) rates of stage I disease were 60-80% and 80-93%, respectively. This study retrospectively evaluated the outcome of stage I FL which was treated with involved field RT in the PET-CT era between 2002 and 2015. Ninety-one patients were enrolled. Five year PFS and OS rates were 73% and 97%, respectively. Relapse occurred in 19 (21%) patients, 74% occurring outside the radiation field. In conclusion, PET-CT staging of clinical stage I FL may contribute to the improved prognosis in patients treated with RT compared to historical cohorts, possibly due to better identification of “genuine” stage I disease. [ABSTRACT FROM AUTHOR]

Published
2018
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23. Severe pneumonia associated with ibrutinib monotherapy for CLL and lymphoma.

Author

Kreiniz, Natalia, Bejar, Jacob, Polliack, Aaron, and Tadmor, Tamar

Subjects
B cell lymphoma, CHRONIC lymphocytic leukemia, HETEROCYCLIC compounds, PNEUMONIA
Abstract

In recent years, there have been major advances in the treatment of chronic lymphocytic leukemia (CLL) particularly since the development of novel therapeutic agents, mostly "biological drugs." One of the obvious advantages of these agents is the decreased rate of infectious complications occurring during the course of therapy, compared to the use of standard immuno-chemotherapy regimens. Here, we describe 3 patients with CLL and 1 with mantle cell lymphoma who developed severe life-threatening pneumonias, during monotherapy with ibrutinib. The first case was a 70-year-old woman with relapsed CLL who developed bilateral pneumonia with hypoxia 1 week after starting ibrutinib. She did not respond to broad-spectrum antibiotics and was treated empirically with trimethoprim-sulphamethoxazole and improved. In the second case, we describe a 76-year-old woman with relapsed CLL who developed recurrent pneumonia after 3 years of treatment with ibrutinib. Presuming that ibrutinib was the cause of pneumonitis with secondary infection, it was stopped with subsequent improvement. The third patient a 67 year-old man died because of severe bilateral necrotizing pneumonia due to invasive aspergillosis and mucormycosis with pulmonary hemorrhage. The fourth patient with relapsed mantle cell lymphoma died because of severe bilateral pneumonia, caused by pseudomonas and candida, despite receiving appropriate antibiotics. From this experience, we hypothesize that the etiology of severe pneumonia associated with ibrutinib treatment is probably multifactorial, involving factors like preexisting immune-suppression, drug induced pneumonitis and infections. We suggest that patients with CLL or other lymphoproliferative disorders with suspected pneumonia during monotherapy with ibrutinib should be very carefully evaluated and need to undergo complete diagnostic workup to establish an exact diagnosis. Understanding which patients with CLL or lymphoma treated with kinase inhibitors are at a higher risk for developing pulmonary complications could be one of the important future challenges, when selecting the best available therapy for these patients. [ABSTRACT FROM AUTHOR]

Published
2018
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24. The Involvement of LAG-3 positive Plasma Cells in the Development of Multiple Myeloma.

Author

Kreiniz N, Eiza N, Tadmor T, Levy Yurkovski I, Matarasso Greenfeld S, Sabag A, Mubariki R, Suriu C, Votinov E, Toubi E, and Vadasz Z

Subjects
Humans, Plasma Cells, Granzymes, Multiple Myeloma, Neoplasms, Plasma Cell, Paraproteinemias, Monoclonal Gammopathy of Undetermined Significance
Abstract

The Lymphocyte-Activation Protein 3 (LAG-3) inhibitory receptor is expressed on regulatory plasma cells (PCs). Micro-environmental cells that express LAG-3 were found to be increased during the progression of smoldering multiple myeloma (SMM). To assess the possible role of LAG-3 expression on regulatory PCs in patients with plasma cell dyscrasia. Purified Cluster of Differentiation 138 (CD138 +) PCs from patients with premalignant conditions, active multiple myeloma (MM), and controls were analyzed for the expression of LAG-3 by flow cytometry. Autologous CD8 + T cells were incubated with sorted LAG-3 pos or LAG-3 neg PCs for 24 h. The expression of granzyme (Grz) in CD8 + T cells was assessed by flow cytometry. LAG-3 expression on PCs in active MM (newly diagnosed and relapse refractory MM) was significantly increased compared to monoclonal gammopathy of undetermined significance (MGUS)/ SMM. Grz expression was significantly decreased in CD8 + T cells incubated with CD138 + LAG-3 pos PCs, compared to CD138 + LAG-3 neg PCs in patients with plasma cell dyscrasia, n = 31, p = 0.0041. LAG-3 expression on malignant PCs can be involved in the development of MM from MGUS by decreasing the expression of Grz in CD8 + T cells.

Published
2023
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25. Acute Renal Failure Associated with Lenalidomide Treatment in Multiple Myeloma: A Rare Occurrence?

Author

Kreiniz N, Khateeb A, Gino-Moor S, Polliack A, and Tadmor T

Subjects
Aged, Female, Humans, Lenalidomide, Male, Middle Aged, Thalidomide adverse effects, Acute Kidney Injury chemically induced, Immunologic Factors adverse effects, Multiple Myeloma drug therapy, Thalidomide analogs & derivatives
Abstract

Renal failure is a frequent complication of multiple myeloma (MM). Recently, the combination of lenalidomide-dexamethasone has become one of the cornerstone regimens for the treatment of MM. Impairment of renal function exacerbation is a rare, but potential, complication of lenalidomide therapy in plasma cell dyscrasias. We present two patients who developed exacerbation of renal function during their first cycle of therapy with lenalidomide. In the first case, we present a 76-year-old-male with MM and impaired renal function, who declined two weeks after initiation of second-line therapy with lenalidomide. His renal functions improved after discontinuation of lenalidomide and with supportive care. In the second case, we describe a 61-year-old woman who was started on lenalidomide for relapsed MM and admitted to intensive care unit three weeks later due to severe renal failure. Despite intensive supportive care, her renal function deteriorated even more and she died. We conclude that renal failure is an uncommon, but serious, potential complication of lenalidomide therapy in plasma cell dyscrasias, particularly MM. Close monitoring of renal function is clearly recommended during this treatment., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Published
2016

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