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1. Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study

Author

Tivey, Ann, Shotton, Rohan, Eyre, Toby A., Lewis, David, Stanton, Louise, Allchin, Rebecca, Walter, Harriet, Miall, Fiona, Zhao, Rui, Santarsieri, Anna, McCulloch, Rory, Bishton, Mark, Beech, Amy, Willimott, Victoria, Fowler, Nicole, Bedford, Claudia, Goddard, Jack, Protheroe, Sam, Everden, Angharad, Tucker, David, Wright, Josh, Dukka, Vasavi, Reeve, Miriam, Paneesha, Shankara, Prahladan, Mahesh, Hodson, Andrew, Qureshi, Iman, Koppana, Manasvi, Owen, Mary, Ediriwickrema, Kushani, Marr, Helen, Wilson, Jamie, Lambert, Jonathan, Wrench, David, Burney, Claire, Knott, Chloe, Talbot, Georgina, Gibb, Adam, Lord, Angela, Jackson, Barry, Stern, Simon, Sutton, Taylor, Webb, Amy, Wilson, Marketa, Thomas, Nicky, Norman, Jane, Davies, Elizabeth, Lowry, Lisa, Maddox, Jamie, Phillips, Neil, Crosbie, Nicola, Flont, Marcin, Nga, Emma, Virchis, Andres, Camacho, Raisa Guerrero, Swe, Wunna, Pillai, Arvind, Rees, Clare, Bailey, James, Jones, Steve, Smith, Susan, Sharpley, Faye, Hildyard, Catherine, Mohamedbhai, Sajir, Nicholson, Toby, Moule, Simon, Chaturvedi, Anshuman, and Linton, Kim

Published
2024
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2. Fludarabine, Cytarabine, Granulocyte Colony-Stimulating Factor, and Idarubicin With Gemtuzumab Ozogamicin Improves Event-Free Survival in Younger Patients With Newly Diagnosed AML and Overall Survival in Patients With NPM1 and FLT3 Mutations

Author

Russell, Nigel H., primary, Wilhelm-Benartzi, Charlotte, additional, Othman, Jad, additional, Dillon, Richard, additional, Knapper, Steven, additional, Batten, Leona M., additional, Canham, Joanna, additional, Hinson, Emily L., additional, Betteridge, Sophie, additional, Overgaard, Ulrik Malthe, additional, Gilkes, Amanda, additional, Potter, Nicola, additional, Mehta, Priyanka, additional, Kottaridis, Panagiotis, additional, Cavenagh, Jamie, additional, Hemmaway, Claire, additional, Arnold, Claire, additional, Freeman, Sylvie D., additional, Dennis, Mike, additional, Kallenbach, Maria, additional, Severinsen, Marianne, additional, Holm, Mette, additional, Maxwell Norgaard, Jan, additional, Beier Ommen, Hans, additional, Culligan, Dominic, additional, Tighe, Jane, additional, Craig, Jenny, additional, Crawley, Charles, additional, Krishnamurthy, Pramila, additional, Sadik, Walid, additional, Smith, Jeffery, additional, Dasgupta, Ranjit, additional, Berkhan, Leanne, additional, Bowett, Peter, additional, Doocey, Richard, additional, Emmett, Shannon, additional, Hawkins, Timothy, additional, Patton, Nigel, additional, Pemberton, Lucy, additional, Milne, Alison, additional, Roy, Ashok, additional, Simpson, Sylwia, additional, Cuthbert, Robert, additional, Finnegan, Damian, additional, Francis McMullin, Mary, additional, Pechey, Victoria, additional, Lovell, Richard, additional, Milligan, Donald, additional, Paneesha, Shankara, additional, Cahalin, Paul, additional, Kelsey, P., additional, Ackroyd, Sam, additional, Wiliams, Adrian, additional, Evely, Roger, additional, Marks, David, additional, Fletcher, Andrew, additional, Al-Ani, Maryam, additional, Ahmed, Khalil, additional, Lush, Richard, additional, Rye, Adam, additional, Cutting, Robert, additional, Welch, Emma, additional, Wodzinski, Mark, additional, Butler, Andrew, additional, Fernyhough, Liam, additional, Ganly, Peter, additional, Gibbons, Steve, additional, Smith, Mark, additional, Spearing, Ruth, additional, Peniket, Andy, additional, Hatcliffe, Faye, additional, Patel, Amit, additional, Lindsay, Kathrine, additional, Brearton, Gillian, additional, Tuegar, Salah, additional, Gandhi Anna Cowley, S., additional, Copplestone, Adrian, additional, Hunter, Hannah, additional, Medd, Patrick, additional, Nokes, Tim, additional, Rule, Simon, additional, Thomas, Wayne, additional, Joseph, Joe, additional, Kaul, Stuti, additional, Sorour, Youssef, additional, Chvuka, Shingi, additional, Mangos, Hilda, additional, Neylon, Annette, additional, Farrell, Katrina, additional, Edwards, Hugh, additional, Hanlon, Katharine, additional, Fail, Tom, additional, Goodrick, Margaret, additional, Heartin, Earnest, additional, Hoyle, Christine, additional, Carr, Robert, additional, Raj, Kavita, additional, Krogh Jensen, Morten, additional, Janmohamed, Riaz, additional, Kaczmarski, Richard, additional, Sugai, Taku, additional, Ademokun, Debo, additional, Chalmers, Isobel, additional, Hodson, Andrew, additional, Gomez, Cesar, additional, Sadullah, Shala, additional, Kwan, Mark, additional, Longmuir, Karyn, additional, Wilson-Morkeh, Isaac, additional, Hunter, Ann, additional, Martin, Murray, additional, Saravanamuttu, Kandeepan, additional, Sidra, Gamal, additional, Burns, Sarah, additional, Gibbs, Simon, additional, Tholouli, Eleni, additional, Aldouri, Maadh, additional, Andrews, Vivienne, additional, Eden, Ayed, additional, Dungarwalla, Moez, additional, White, Denise, additional, Laird, Jane, additional, Mitchell, Lindsey, additional, Murphy, John, additional, Paterson, Pamela, additional, Raafat, Alaeddin, additional, Mannari, Deepak, additional, Davies, Simon, additional, Austen, Belinda, additional, Allford, Sarah, additional, Kakalamudi, Sudhakar, additional, Basu, Supratik, additional, Hada, Sunil, additional, Jacob, Abraham, additional, MacWhonell, Alan, additional, McCaig, Alison, additional, Gelly, Keith, additional, Kerr, Ron, additional, Meiklejohn, David, additional, Tauro, Sudhir, additional, Lawes, Matthew, additional, Bowen, Angela, additional, Krishnamurthy, Suchitra, additional, Byrne, Jenny, additional, Dasgupta, Emma, additional, Russell, Nigel, additional, Stokley, Simone, additional, Friis, Lone, additional, Marcher, Claus, additional, Bake, Bart, additional, Chapple, Mary, additional, Moreton, Paul, additional, Omran, Asad, additional, Patil, Kavita, additional, Wright, David, additional, Jack, Fergus, additional, Maddams, Rebecca, additional, Corser, Robert, additional, Cranfield, Tanya, additional, Dignum, Helen, additional, Ganczakowski, Mary, additional, Jones, Christopher, additional, Craddock, Charles, additional, Moss, Paula, additional, Murray, Jim, additional, Craig, Joanne, additional, Forsyth, Peter, additional, Lush, Chris, additional, Wei Bjerrum, Ole, additional, Borregaard, Niels, additional, Kampmann, Peter, additional, Kjeldsen, Lars, additional, Juul Nielsen, Ove, additional, Niemann, Carsten, additional, Lykke Petersen, Soeren, additional, Udby Peter Møller, Lene, additional, Alfred, Arun, additional, Barker, Helen, additional, Went, Richard, additional, Groch, Henri, additional, Mucklow, Stuart, additional, Sampson, Rebecca, additional, Chacko, Joseph, additional, Hall, Rachel, additional, Walewska, Renata, additional, Creach, Desmond, additional, Pottinger, Bryson, additional, Addada, Juanah (Jo), additional, Hamilton, Malcolm, additional, Kerr, Paul, additional, Ngu, Loretta, additional, Rudin, Claudius, additional, Ruell, Jackie, additional, Dalley, Chris, additional, Kaur, Harpreet, additional, Reilly, John, additional, Snowden, John, additional, Ferguson, Paul, additional, Dyer, Peter, additional, Chandra, Deepak, additional, DeVos, Johannes, additional, Grey-Davies, Elisabeth, additional, Hendry, Louise, additional, Corbett, Timothy, additional, Crowe, Josephine, additional, Knechtli, Christopher, additional, Wexler, Sarah, additional, Fernandes, Savio, additional, Neilson, Jeff, additional, Houghton, John, additional, Jowitt, Simon, additional, Thomas-Dewing, Rowena, additional, Williams, Mark, additional, Zaman, Sonya, additional, Cullis, Jonathan, additional, Everington, Tamara, additional, Grand, Effie, additional, Hasan, Yasmin, additional, Murrin, Richard, additional, Wandoo, Farooq, additional, Ismail, Saad, additional, Mohite, Unmesh, additional, Sati, Hamdi, additional, Jenner, Matthew, additional, Orchard, Kim, additional, Richardson, Deborah, additional, McCloskey, Kayleigh, additional, Xu Chin, Kate, additional, Fenella Willis, Neoh, additional, Sud, Amit, additional, Gharib, Maged, additional, Nicholson, Toby, additional, Bowen, David, additional, Janes, Sarah, additional, Eagleton, Helen, additional, O'Hea, Anne-Marie, additional, Pattinson, Jonathan, additional, Hervey, Victoria, additional, Lyons, Simon, additional, Marshall, Scott, additional, Nicolle, Annette, additional, Vavyla, Maria, additional, Burgess, Jordan, additional, Somervaille, Tim, additional, Somerfield, Sven, additional, Mamat, Mohd, additional, Tomlins, Jo, additional, Salesh, Sana, additional, David, Marianna, additional, Maddox, Jamie, additional, Plews, Diane, additional, Dang, Ray, additional, Potter, Mike, additional, Ellis, Lauren, additional, Nicholson, Emma, additional, Keat, Sally, additional, Ahmed Alhassani, Thubeena M., additional, Anjum, Farahn, additional, Chatterjee, Poulami, additional, Stanchev, Atanas, additional, Peters, Jayne, additional, Lindsay-Holmes Srividhya, Sarah, additional, Chodhouri, Senthil S., additional, Eve, Heather, additional, Smith, Steve, additional, Roberts, Patrick, additional, Rymes, Nicholas, additional, Zhao New Oo, Rui, additional, Ardeshna, Kirit, additional, Blombery, Piers, additional, Khwaja, Asim, additional, Linch, David, additional, Popat, Rakesh, additional, Virchis, Andres, additional, Yong, Kwee, additional, McIntyre, Victoria, additional, Horne, Gillian, additional, Bokhari, Syed, additional, Borg, Anton, additional, Chapman, Oliver, additional, Harrison, Beth, additional, Jackson, Nicholas, additional, Jobanputra, Shailesh, additional, Narayanan, Mekkali, additional, Rose, Peter, additional, Oun, Hajer, additional, Powell, Matthew, additional, Gilles, Julie, additional, Laing, Alison, additional, Devanny, Ian, additional, Haskins, Lea, additional, Micallef-Eynaud, Paul, additional, Maclean, Peter, additional, Alvares, Caroline, additional, Kell, Jonathan, additional, Knapper, Steve, additional, Davidson, Kerri, additional, McLintock, Lorna, additional, Rogers, Stephen, additional, Williamson, Peter, additional, Corbett, Gillian, additional, Goodman, Hugh, additional, Islam, Shahid, additional, Pullon, Humphrey, additional, Johnson, Peter, additional, Roddie, P.H., additional, Maughan, Elizabeth, additional, Mills, Juliet, additional, Shafeek, Salim, additional, Narat, Santosh, additional, Aitchison, Robin, additional, Bond, Lee, additional, Munro, Laura, additional, and Edwards, David, additional

Published
2024
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3. Ibrutinib as first line therapy for mantle cell lymphoma: A multicentre, real-world UK study

Author

Tivey, Ann, primary, Shotton, Rohan, additional, Eyre, Toby A., additional, Lewis, David, additional, Stanton, Louise, additional, Allchin, Rebecca, additional, Walter, Harriet Sarah, additional, Miall, Fiona, additional, Zhao, Rui, additional, Santarsieri, Anna, additional, McCulloch, Rory, additional, Bishton, Mark, additional, Beech, Amy, additional, Willimott, Victoria Clare, additional, Fowler, Nicole, additional, Bedford, Claudia, additional, Goddard, Jack, additional, Protheroe, Samuel, additional, Everden, Angharad, additional, Tucker, David L, additional, Wright, Joshua, additional, Dukka, Srivasavi, additional, Thomson, Miriam, additional, Paneesha, Shankara, additional, Prahladan, Mahesh, additional, Hodson, Andrew, additional, Qureshi, Iman, additional, Koppana, Manasvi, additional, Owen, Mary, additional, Ediriwickrema, Kushani, additional, Marr, Helen, additional, Wilson, Jamie, additional, Lambert, Jonathan, additional, Wrench, David J, additional, Burney, Claire N, additional, Knott, Chloe, additional, Talbot, Georgina, additional, Gibb, Adam, additional, Lord, Angela, additional, Jackson, Barry, additional, Stern, Simon, additional, Sutton, Taylor, additional, Webb, Amy Caitlin, additional, Wilson, Marketa, additional, Thomas, Nicky, additional, Norman, Jane, additional, Davies, Elizabeth, additional, Lowry, Lisa, additional, Maddox, Jamie, additional, Phillips, Neil, additional, Crosbie, Nicola, additional, Flont, Marcin, additional, Nga, Emma LM, additional, Virchis, Andres, additional, Guerrero Camacho, Raisa, additional, Swe, Wunna, additional, Pillai, Arvind Radhakrishna, additional, Rees, Clare, additional, Bailey, James, additional, Jones, Steve Gareth, additional, Smith, Susan, additional, Sharpley, Faye, additional, Hildyard, Catherine, additional, Mohamedbhai, Sajir, additional, Nicholson, Toby, additional, Moule, Simon, additional, Chaturvedi, Anshuman, additional, and Linton, Kim, additional

Published
2023
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4. RNA-seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature

Author

Chapman, Michael A., Sive, Jonathan, Ambrose, John, Roddie, Claire, Counsell, Nicholas, Lach, Anna, Abbasian, Mahnaz, Popat, Rakesh, Cavenagh, Jamie D., Oakervee, Heather, Streetly, Matthew J., Schey, Stephen, Koh, Mickey, Willis, Fenella, Virchis, Andres E., Crowe, Josephine, Quinn, Michael F., Cook, Gordon, Crawley, Charles R., Pratt, Guy, Cook, Mark, Braganza, Nivette, Adedayo, Toyin, Smith, Paul, Clifton-Hadley, Laura, Owen, Roger G., Sonneveld, Pieter, Keats, Jonathan J., Herrero, Javier, and Yong, Kwee

Published
2018
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5. Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia

Author

Cross, Nicholas C. P., Hoade, Yvette, Tapper, William J., Carreno-Tarragona, Gonzalo, Fanelli, Tiziana, Jawhar, Mohamad, Naumann, Nicole, Pieniak, Iwo, Lübke, Johannes, Ali, Sahra, Bhuller, Kaljit, Burgstaller, Sonja, Cargo, Catherine, Cavenagh, Jamie, Duncombe, Andrew S., Das-Gupta, Emma, Evans, Paul, Forsyth, Peter, George, Philip, Grimley, Charlotte, Jack, Fergus, Munro, Laura, Mehra, Varun, Patel, Kavita, Rismani, Ali, Sciuccati, Gabriela, Thomas-Dewing, Rowena, Thornton, Patrick, Virchis, Andres, Watt, Simon, Wallis, Louise, Whiteway, Alastair, Zegocki, Kris, Bain, Barbara J., Reiter, Andreas, and Chase, Andrew

Published
2019
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8. A randomised evaluation of low-dose cytosine arabinoside (ara-C) plus tosedostat versus low-dose ara-C in older patients with acute myeloid leukaemia: results of the LI-1 trial

Author

Dennis, Mike, Burnett, Alan, Hills, Robert, Thomas, Ian, Ariti, Cono, Severinsen, Marianne T., Hemmaway, Claire, Greaves, Paul, Clark, Richard E., Copland, Mhairi, Russell, Nigel, Kallenbach, Maria, Culligan, Dominic, Duncan, Caroline, Krishnamurthy, Pramila, Cuthbert, Ann, Patalappa, Chetan, Spanoudakis, Michail, Galvani, David, Berkahn, I., Patton, N., Pemberton, Lucy, Virchis, Andres, Jasani, Parag, Parker, Anne, Arnold, Claire, Cuthbert, Robert, Finnega, Damien, Nikolousis, Manos, Pratt, Guy, Cahalin, Paul, Ackroyd, Sam, Mehta, Priyanka, Protheroe, Rachel, Weinkove, Robert, Ali, Sara, Welch, Emma, Smith, Mark, Spearing, Ruth, Vyas, Paresh, Campbell, Gavin, Hamblin, Mike, Wood, Marion, Gupta, Sunil, Westonsmith, Simon, Pillai, Arvind, Hunter, Hannah, Kjeldsen, Lars, Niemann, Carsten U., and Khan, Asif

Subjects
acute leukaemia, Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, medicine.medical_treatment, Glycine, chemotherapy, Hydroxamic Acids, elderly, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, AML, Older patients, Internal medicine, Tosedostat, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Enzyme Inhibitors, Aged, Aged, 80 and over, Chemotherapy, business.industry, Hazard ratio, Age Factors, Cytarabine, Hematology, Odds ratio, Middle Aged, Survival Analysis, Confidence interval, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Toxicity, Female, Myeloid leukaemia, business, 030215 immunology
Abstract

Older patients with acute myeloid leukaemia (AML) account for nearly half of those with the disease. Because they are perceived to be unfit for, unwilling to receive, or unlikely to benefit from conventional chemotherapy they represent an important unmet need. Tosedostat is a selective oral aminopeptidase inhibitor, which in phase I/II trials showed acceptable toxicity and encouraging efficacy. We report the only randomised study of low-dose cytosine arabinoside (LDAC) combined with tosedostat (LDAC-T) versus LDAC in untreated older patients not suitable for intensive treatment. A total of 243 patients were randomised 1:1 as part of the 'Pick-a-Winner' LI-1 trial. There was a statistically non-significant increase in the complete remission (CR) rate with the addition of tosedostat, LDAC-T 19% versus LDAC 12% [odds ratio (OR) 0·61, 95% confidence interval (CI) 0·30-1·23; P = 0·17]. For overall response (CR+CR with incomplete recovery of counts), there was little evidence of a benefit to the addition of tosedostat (25% vs. 18%; OR 0·68, 95% CI 0·37-1·27; P = 0·22). However, overall survival (OS) showed no difference (2-year OS 16% vs. 12%, hazard ratio 0·97, 95% CI 0·73-1·28; P = 0·8). Exploratory analyses failed to identify any subgroup benefitting from tosedostat. Despite promising pre-clinical, early non-randomised clinical data with acceptable toxicity and an improvement in response, we did not find evidence that the addition of tosedostat to LDAC produced a survival benefit in this group of patients with AML. International Standard Randomised Controlled Trial Number: ISRCTN40571019.

Published
2021

9. A randomised evaluation of low-dose cytosine arabinoside (ara-C) plus tosedostat versus low-dose ara-C in older patients with acute myeloid leukaemia:results of the LI-1 trial

Author

Dennis, Mike, Burnett, Alan, Hills, Robert, Thomas, Ian, Ariti, Cono, Severinsen, Marianne T., Hemmaway, Claire, Greaves, Paul, Clark, Richard E., Copland, Mhairi, Russell, Nigel, Kallenbach, Maria, Culligan, Dominic, Duncan, Caroline, Krishnamurthy, Pramila, Cuthbert, Ann, Patalappa, Chetan, Spanoudakis, Michail, Galvani, David, Berkahn, I., Patton, N., Pemberton, Lucy, Virchis, Andres, Jasani, Parag, Parker, Anne, Arnold, Claire, Cuthbert, Robert, Finnega, Damien, Nikolousis, Manos, Pratt, Guy, Cahalin, Paul, Ackroyd, Sam, Mehta, Priyanka, Protheroe, Rachel, Weinkove, Robert, Ali, Sara, Welch, Emma, Smith, Mark, Spearing, Ruth, Vyas, Paresh, Campbell, Gavin, Hamblin, Mike, Wood, Marion, Gupta, Sunil, Westonsmith, Simon, Pillai, Arvind, Hunter, Hannah, Kjeldsen, Lars, Niemann, Carsten U., Khan, Asif, Dennis, Mike, Burnett, Alan, Hills, Robert, Thomas, Ian, Ariti, Cono, Severinsen, Marianne T., Hemmaway, Claire, Greaves, Paul, Clark, Richard E., Copland, Mhairi, Russell, Nigel, Kallenbach, Maria, Culligan, Dominic, Duncan, Caroline, Krishnamurthy, Pramila, Cuthbert, Ann, Patalappa, Chetan, Spanoudakis, Michail, Galvani, David, Berkahn, I., Patton, N., Pemberton, Lucy, Virchis, Andres, Jasani, Parag, Parker, Anne, Arnold, Claire, Cuthbert, Robert, Finnega, Damien, Nikolousis, Manos, Pratt, Guy, Cahalin, Paul, Ackroyd, Sam, Mehta, Priyanka, Protheroe, Rachel, Weinkove, Robert, Ali, Sara, Welch, Emma, Smith, Mark, Spearing, Ruth, Vyas, Paresh, Campbell, Gavin, Hamblin, Mike, Wood, Marion, Gupta, Sunil, Westonsmith, Simon, Pillai, Arvind, Hunter, Hannah, Kjeldsen, Lars, Niemann, Carsten U., and Khan, Asif

Abstract

Older patients with acute myeloid leukaemia (AML) account for nearly half of those with the disease. Because they are perceived to be unfit for, unwilling to receive, or unlikely to benefit from conventional chemotherapy they represent an important unmet need. Tosedostat is a selective oral aminopeptidase inhibitor, which in phase I/II trials showed acceptable toxicity and encouraging efficacy. We report the only randomised study of low-dose cytosine arabinoside (LDAC) combined with tosedostat (LDAC-T) versus LDAC in untreated older patients not suitable for intensive treatment. A total of 243 patients were randomised 1:1 as part of the ‘Pick-a-Winner’ LI-1 trial. There was a statistically non-significant increase in the complete remission (CR) rate with the addition of tosedostat, LDAC-T 19% versus LDAC 12% [odds ratio (OR) 0·61, 95% confidence interval (CI) 0·30–1·23; P = 0·17]. For overall response (CR+CR with incomplete recovery of counts), there was little evidence of a benefit to the addition of tosedostat (25% vs. 18%; OR 0·68, 95% CI 0·37–1·27; P = 0·22). However, overall survival (OS) showed no difference (2-year OS 16% vs. 12%, hazard ratio 0·97, 95% CI 0·73–1·28; P = 0·8). Exploratory analyses failed to identify any subgroup benefitting from tosedostat. Despite promising pre-clinical, early non-randomised clinical data with acceptable toxicity and an improvement in response, we did not find evidence that the addition of tosedostat to LDAC produced a survival benefit in this group of patients with AML. International Standard Randomised Controlled Trial Number: ISRCTN40571019.

Published
2021

11. Thrombotic microangiopathy in untreated myeloma patients receiving carfilzomib, cyclophosphamide and dexamethasone on the CARDAMON study

Author

Camilleri, Marquita, primary, Cuadrado, Maria, additional, Phillips, Elizabeth, additional, Wilson, William, additional, Jenner, Richard, additional, Pang, Gavin, additional, Kamora, Sumaiya, additional, Streetly, Matthew, additional, Popat, Rakesh, additional, Bygrave, Ceri, additional, Owen, Roger, additional, Cavenagh, James, additional, Chapman, Mike, additional, Sive, Jonathan, additional, Eccersley, Lydia, additional, Sheaff, Michael, additional, Benjamin, Reuben, additional, Ramasamy, Karthik, additional, Cook, Gordon, additional, Virchis, Andres, additional, Chavda, Selina J., additional, Clifton‐Hadley, Laura, additional, Scully, Marie Anne, additional, and Yong, Kwee, additional

Published
2021
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12. The addition of bendamustine to brentuximab vedotin leads to improved rates of complete metabolic remission in children, adolescents and young adults with relapsed and refractory classical Hodgkin lymphoma: a retrospective single‐centre series

Author

McMillan, Annabel, primary, O'Neill, Aideen T., additional, Townsend, William, additional, Lambert, Jonathan., additional, Virchis, Andres, additional, Shah, Raakhee, additional, Menezes, Leon, additional, Humphries, Paul, additional, Von Both, Kirsten, additional, Grandage, Victoria, additional, Carpenter, Ben, additional, Hough, Rachael, additional, Ardeshna, Kirit M., additional, and Daw, Stephen, additional

Published
2021
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14. A Phase I Study Evaluating the Safety and Persistence of Allorestricted WT1-TCR Gene Modified Autologous T Cells in Patients with High-Risk Myeloid Malignancies Unsuitable for Allogeneic Stem Cell Transplantation

Author

Morris, Emma C, primary, Tendeiro-Rego, Rita, additional, Richardson, Rachel, additional, Fox, Thomas A, additional, Sillito, Francesca, additional, Holler, Angelika, additional, Thomas, Sharyn, additional, Xue, Shao-An, additional, Martínez-Dávila, Irma Alicia, additional, Nicholson, Emma, additional, Ahmadi, Mandana, additional, King, Judith, additional, Kottaridis, Panagiotis, additional, Chakraverty, Ronjon, additional, Thomson, Kirsty, additional, Robinson, Stephen, additional, Virchis, Andres E., additional, Khwaja, Asim, additional, Quaye, Michelle, additional, Zhan, Hong, additional, Qasim, Waseem, additional, Himoudi, Nourredine, additional, Barry, Jacqueline, additional, Mount, Natalie, additional, Gaskell, Terri, additional, Sharpe, Michaela, additional, Inman, Shannon M, additional, Gunter, Kurt C., additional, and Stauss, Hans, additional

Published
2019
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15. Efficacy and Safety of Carfilzomib at 56mg/m2 with Cyclophosphamide and Dexamethasone (K56Cd) in Newly Diagnosed Multiple Myeloma Patients Followed By ASCT or K56Cd Consolidation: Initial Results of the Phase 2 Cardamon Study

Author

Yong, Kwee, primary, Popat, Rakesh, primary, Wilson, William, primary, Pang, Gavin, primary, Jenner, Richard, primary, De Tute, Ruth M, primary, Ramasamy, Karthik, primary, Streetly, Matthew, primary, Cavenagh, Jamie, primary, Sive, Jonathan, primary, Chapman, Michael, primary, Bygrave, Ceri, primary, Phillips, Beth, primary, Chavda, Selina J, primary, Virchis, Andres E., primary, Benjamin, Reuben, primary, Arnott, Sarah, primary, Willis, Fenella, primary, Hassan, Sandra, primary, Moore, Sally, primary, Clifton-Hadley, Laura, primary, and Owen, Roger G, primary

Published
2019
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18. Outcomes of newly diagnosed multiple myeloma with deferred ASCT after achieving ≥VGPR following PAD induction in the Phase 2 PADIMAC study

Author

Chan, Wei Yee, primary, Counsell, Nicholas, additional, Popat, Rakesh, additional, De Tute, Ruth, additional, De-silva, Dunnya, additional, Phillips, Elizabeth, additional, Cavenagh, Jamie, additional, Adedayo, Toyin, additional, Braganca, Nivette, additional, Roddie, Claire, additional, Streetly, Matthew, additional, Schey, Steve, additional, Koh, Mickey, additional, Crowe, Josephine, additional, Quinn, Michael, additional, Morris, Curly, additional, D'Sa, Shirley, additional, Virchis, Andres, additional, Cook, Gordon, additional, Crawley, Charles, additional, Pratt, Guy, additional, Cook, Mark, additional, Clifton-Hadley, Laura, additional, Rabin, Neil, additional, Owen, Roger, additional, and Yong, Kwee, additional

Published
2019
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19. Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia

Author

Cross, Nicholas C. P., primary, Hoade, Yvette, additional, Tapper, William J., additional, Carreno-Tarragona, Gonzalo, additional, Fanelli, Tiziana, additional, Jawhar, Mohamad, additional, Naumann, Nicole, additional, Pieniak, Iwo, additional, Lübke, Johannes, additional, Ali, Sahra, additional, Bhuller, Kaljit, additional, Burgstaller, Sonja, additional, Cargo, Catherine, additional, Cavenagh, Jamie, additional, Duncombe, Andrew S., additional, Das-Gupta, Emma, additional, Evans, Paul, additional, Forsyth, Peter, additional, George, Philip, additional, Grimley, Charlotte, additional, Jack, Fergus, additional, Munro, Laura, additional, Mehra, Varun, additional, Patel, Kavita, additional, Rismani, Ali, additional, Sciuccati, Gabriela, additional, Thomas-Dewing, Rowena, additional, Thornton, Patrick, additional, Virchis, Andres, additional, Watt, Simon, additional, Wallis, Louise, additional, Whiteway, Alastair, additional, Zegocki, Kris, additional, Bain, Barbara J., additional, Reiter, Andreas, additional, and Chase, Andrew, additional

Published
2018
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24. Clinical Characteristics and Treatment with Various Tyrosine Kinase Inhibitors in Patients with ETV6-ABL1 positive Eosinophilia-Associated Myeloproliferative Neoplasms

Author

Reiter, Andreas, primary, Ahmadova, Gunay, additional, Jawhar, Mohamad, additional, Virchis, Andres, additional, Somervaille, Tim, additional, Williams, Mark, additional, Schönberger, Bernd, additional, Frewin, Rebecca, additional, Jost, Philipp J., additional, Maschke, Annett, additional, Keller, Peter, additional, Haferlach, Torsten, additional, Naumann, Nicole, additional, Schwaab, Juliana, additional, Fabarius, Alice, additional, Hofmann, Wolf-Karsten, additional, Haferlach, Claudia, additional, Cross, Nicholas C.P., additional, and Metzgeroth, Georgia, additional

Published
2016
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25. RNA Sequencing of Newly Diagnosed Multiple Myeloma to Identify a Predictive Signature for Proteasome Inhibitor-Based Therapy

Author

Sive, Jonathan I, primary, Ambrose, John C, additional, Yong, Kwee L, additional, Roddie, Claire, additional, Counsell, Nicholas, additional, Smith, Paul, additional, Braganca, Nivette, additional, Adadayo, Toyin, additional, Popat, Rakesh, additional, Cavenagh, James D, additional, Owen, Roger G, additional, Streetly, Matthew, additional, Schey, Stephen A, additional, Koh, Mickey, additional, Crowe, Josephine, additional, Quinn, Michael F, additional, D'Sa, Shirley, additional, Virchis, Andres, additional, Cook, Gordon, additional, Crawley, Charles, additional, Pratt, Guy E, additional, Cook, Mark, additional, and Chapman, Michael A, additional

Published
2016
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26. Ofatumumab is a feasible alternative anti‐CD20 therapy in patients intolerant of rituximab.

Author

Chen, Lucia Y., Shah, Raakhee, Cwynarski, Kate, Lambert, Jonathan, McNamara, Christopher, Mohamedbhai, Sajir G., Virchis, Andres, Townsend, William, D'Sa, Shirley, and Ardeshna, Kirit M.

Abstract

The article informs on a study conducted for analysing the feasibility of ofatumumab drug as an alternative anti-CD20 therapy in patients intolerant of rituximab drug. It informs that infusion-related reactions (IRR) to rituximab occurred among patients; and patients intolerant of rituximab due to IRRs are likely to have a worse outcome in terms of progression-free survival and overall survival. It also mentions that ofatumumab is the feasible alternative for rituximab.

Published
2019
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27. Recurrent activating STAT5BN642H mutation in myeloid neoplasms with eosinophilia

Author

Cross, Nicholas C. P., Hoade, Yvette, Tapper, William J., Carreno-Tarragona, Gonzalo, Fanelli, Tiziana, Jawhar, Mohamad, Naumann, Nicole, Pieniak, Iwo, Lübke, Johannes, Ali, Sahra, Bhuller, Kaljit, Burgstaller, Sonja, Cargo, Catherine, Cavenagh, Jamie, Duncombe, Andrew S., Das-Gupta, Emma, Evans, Paul, Forsyth, Peter, George, Philip, Grimley, Charlotte, Jack, Fergus, Munro, Laura, Mehra, Varun, Patel, Kavita, Rismani, Ali, Sciuccati, Gabriela, Thomas-Dewing, Rowena, Thornton, Patrick, Virchis, Andres, Watt, Simon, Wallis, Louise, Whiteway, Alastair, Zegocki, Kris, Bain, Barbara J., Reiter, Andreas, and Chase, Andrew

Abstract

Determining the underlying cause of persistent eosinophilia is important for effective clinical management but remains a diagnostic challenge in many cases. We identified STAT5BN642H, an established oncogenic mutation, in 27/1715 (1.6%) cases referred for investigation of eosinophilia. Of the 27 mutated cases, a working diagnosis of hypereosinophilic syndrome (HES; n= 7) or a myeloid neoplasm with eosinophilia (n= 20) had been made prior to the detection of STAT5BN642H. Myeloid panel analysis identified a median of 2 additional mutated genes (range 0–4) with 4 cases having STAT5BN642H as a sole abnormality. STAT5BN642H was absent in cultured T cells of 4/4 positive cases. Individuals with SF3B1mutations (9/27; 33%) or STAT5BN642H as a sole abnormality had a markedly better overall survival compared to cases with other additional mutations (median 65 months vs. 14 months; hazard ratio = 8.1; P< 0.001). The overall survival of STAT5B-mutated HES cases was only 30 months, suggesting that these cases should be reclassified as chronic eosinophilic leukemia, not otherwise specified (CEL-NOS). The finding of STAT5BN642H as a recurrent mutation in myeloid neoplasia with eosinophilia provides a new diagnostic and prognostic marker as well as a potential target for therapy.

Published
2019
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28. Outcomes of Stratification to ASCT or Not Based on Depth of Response: Results of a Phase 2 Trial Assessing the Impact of Minimal Residual Disease (MRD) in Multiple Myeloma Patients with Deferred ASCT (PADIMAC)

Author

Popat, Rakesh, De Tute, Ruth Mary, Counsell, Nicholas, De-Silva, Dunnya, Phillips, Beth, Cavenagh, James D, Adedayo, Toyin, Braganza, Nivette, Roddie, Claire, Streetly, Mathew, Schey, Stephen, Koh, Mickey, Crowe, Josephine, Quinn, Michael F., D'Sa, Shirley, Virchis, Andres E., Cook, Gordon, Crawley, Charles R, Pratt, Guy, Cook, Mark, Smith, Paul, Clifton-Hadley, Laura, Rabin, Neil, Owen, Roger G, and Yong, Kwee

Published
2017
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29. A Seven Gene Signature to Distinguish Bortezomib- and Lenalidomide-Responsive Myeloma: Rnaseq from the Padimac Study

Author

Chapman, Michael, Sive, Jonathan, Ambrose, John, Roddie, Claire, Counsell, Nicholas, Smith, Paul, Braganza, Nivette, Adedayo, Toyin, Popat, Rakesh, Cavenagh, James D, Streetly, Matthew J., Owen, Roger G., Schey, Stephen, Koh, Mickey, Crowe, Josephine, Quinn, Michael F., D'Sa, Shirley, Virchis, Andres E., Cook, Gordon, Crawley, Charles R, Pratt, Guy, Cook, Mark, Clifton-Hadley, Laura, Herrero, Javier, and Yong, Kwee

Published
2017
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30. Subcutaneous PAD As Induction Therapy for Patients with Newly Diagnosed Myeloma: A Phase 2 Trial Assessing the Impact of Minimal Residual Disease (MRD) in Patients with Deferred Autologous Stem Cell Transplantation (PADIMAC)

Author

Popat, Rakesh, primary, Cavenagh, James D, additional, Owen, Roger G, additional, Streetly, Matthew, additional, Schey, Stephen A, additional, Koh, Mickey, additional, Crowe, Josephine, additional, Quinn, Michael F., additional, D'Sa, Shirley, additional, Virchis, Andres, additional, Cook, Gordon, additional, Crawley, Charles, additional, Pratt, Guy, additional, Cook, Mark, additional, Oakervee, Heather E., additional, Counsell, Nicholas, additional, Adedayo, Toyin, additional, Evans, Alison, additional, Braganca, Nivette, additional, Smith, Paul, additional, lyons-Lewis, Janet, additional, Rabin, Neil, additional, and Yong, Kwee L, additional

Published
2014
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33. Autologous Stem Cell Transplantation Using BEAM Conditioning Is Highly Effective in Patients with Follicular Lymphoma Regardless of Prior Rituximab Exposure

Author

Kothari, Jaimal, primary, Ljubic, Antonia, additional, Peggs, Karl S, additional, Thomson, Kirsty, additional, Morris, Emma, additional, Virchis, Andres E., additional, Lambert, Jonathan, additional, Goldstone, Anthony H, additional, Linch, David C, additional, and Ardeshna, Kirit M, additional

Published
2011
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37. A novel treatment approach for low grade lymphoproliferative disorders using PKC412 (CGP41251), an inhibitor of protein kinase C

Author

Virchis, Andres, primary, Ganeshaguru, Kanagasabai, additional, Hart, Steve, additional, Jones, Dylan, additional, Fletcher, Linda, additional, Wright, Faith, additional, Wickremasinghe, Ranmohan, additional, Man, Anthony, additional, Csermak, Katalin, additional, Meyer, Thomas, additional, Fabbro, Doriano, additional, Champain, Kate, additional, Yap, Alan, additional, Prentice, H Grant, additional, and Mehta, Atul, additional

Published
2002
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38. Efficacy and Safety of Carfilzomib at 56mg/m2with Cyclophosphamide and Dexamethasone (K56Cd) in Newly Diagnosed Multiple Myeloma Patients Followed By ASCT or K56Cd Consolidation: Initial Results of the Phase 2 Cardamon Study

Author

Yong, Kwee, Popat, Rakesh, Wilson, William, Pang, Gavin, Jenner, Richard, De Tute, Ruth M, Ramasamy, Karthik, Streetly, Matthew, Cavenagh, Jamie, Sive, Jonathan, Chapman, Michael, Bygrave, Ceri, Phillips, Beth, Chavda, Selina J, Virchis, Andres E., Benjamin, Reuben, Arnott, Sarah, Willis, Fenella, Hassan, Sandra, Moore, Sally, Clifton-Hadley, Laura, and Owen, Roger G

Abstract

Introduction:Carfilzomib (20/36mg/m2) triplets with Lenalidomide-Dexamethasone (KRd), or Cyclophosphamide-Dexamethasone (KCd) are safe and effective in patients with newly diagnosed multiple myeloma(NDMM). The higher dose of 56mg/m2is effective as a doublet with Dexamethasone in the relapsed setting, but there is limited data on this dose in triplet combinations in the frontline setting.

Published
2019
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40. Clinical Characteristics and Treatment with Various Tyrosine Kinase Inhibitors in Patients with ETV6-ABL1positive Eosinophilia-Associated Myeloproliferative Neoplasms

Author

Reiter, Andreas, Ahmadova, Gunay, Jawhar, Mohamad, Virchis, Andres, Somervaille, Tim, Williams, Mark, Schönberger, Bernd, Frewin, Rebecca, Jost, Philipp J., Maschke, Annett, Keller, Peter, Haferlach, Torsten, Naumann, Nicole, Schwaab, Juliana, Fabarius, Alice, Hofmann, Wolf-Karsten, Haferlach, Claudia, Cross, Nicholas C.P., and Metzgeroth, Georgia

Abstract

The ETV6-ABL1fusion gene, as consequence of a t(9;12)(q34;p13), is a rare but recurrent genetic aberration found in chronic or blast phase of eosinophilia-associated myeloproliferative neoplasms (MPN-eo) and de novoacute B-cell lymphoblastic leukemias (B-ALL) or lymphoblastic T-cell lymphomas (T-LBL). Here, we sought to evaluate a) relevant clinical characteristics, b) treatment options and c) survival in 7 ETV6-ABL1positive patients (male, n=4; median age 46 years; range 20-61). Cytogenetic analyses revealed a conventional reciprocal translocation t(9;12)(q34;p13) in 3 cases, an ins(12;9)(p13;q34q22) and a normal karyotype in one patient each, and a complex karyotype in 2 patients. In all cases, ETV6-ABL1was confirmed by FISH analysis and/or RT-PCR. Histopathological diagnoses of the hypercellular bone marrow (BM) included atypical chronic myeloid leukemia (n=3), MPN-eo (n=3, concomitant T-LBL in one patient) or chronic myelomonocytic leukemia (n=1). In peripheral blood, all patients presented with left shifted leukocytosis (median 84 x 109/l, range 21-143) and significant (>1.5 x 109/l) eosinophilia (median 6.1 x 109/l, range 2.0-7.1) but without increased blast cells. Splenomegaly was present in 60% of patients. After a median of 3 months (range 0-6) from diagnosis, all patients were treated with a TKI (imatinib, n=5; dasatinib, n=1; nilotinib, n=1) at standard doses. On dasatinib (#2) or nilotinib (#3), 2 patients achieved a complete hematologic remission (CHR) within 3 months and complete cytogenetic remission (CCR) after 5 months (#3) or complete molecular remission (CMR) after 18 months (#2), respectively (Figure). On imatinib (n=5), 2 of 5 patients (#4 and #5) achieved a CHR within 3 months with loss of CHR after 9 (#4) and 5 months (#5), respectively. Patient #4 developed a myeloid sarcoma. After local radiation, he received an allogeneic stem cell transplant (SCT) but died 8 months later due to GvHD while in CMR. Patient #5 switched to nilotinib and achieved a CCR and CMR after 3 and 10 months, respectively. Patient #1 has not achieved a significant response after 4 months on imatinib. Patient #6 showed progressive disease within 2 months on imatinib, but achieved a rapid CHR and durable CCR and CMR on dasatinib after 13 and 14 months, respectively. Patient #7 presented with a classical myeloid/lymphoid (T-LBL) neoplasm with eosinophilia (MLN-eo) according to the WHO classification. On imatinib, a regression of lymphadenopathy, but persistence of leukocytosis and eosinophilia was observed. With increasing leukocytosis and reappearance of lymphadenopathy, the patient was switched to dasatinib (9 months), followed by nilotinib (2 months). The responses were only partial and transient and the patient died 23 months after diagnosis with myeloid blast phase (secondary acute myeloid leukemia). Overall, after a median treatment time of 22 months (range, 3-58), 4 patients are in CCR (n=1, patient #3) or CMR (n=3; patients #2, #5, #6) while on a second generation TKI and two patients (#4, #7) have died. On imatinib, none of 5 patients achieved a CCR or CMR. We conclude that a) cytogenetic analysis is an important tool for the identification of potential TK fusion genes such as ETV6-ABL1, b) ETV6-ABL1is a candidate for incorporation into the WHO-defined subcategory ´MLN-eo´, c) patients with MPN-eo can achieve durable CHR, CCR or CMR on TKI with second generation TKI being more effective than imatinib d) close monitoring by cytogenetics, FISH and RT-PCR is recommended for early identification of inadequate response or resistance.

Published
2016
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41. Actions of the selective protein kinase C inhibitor PKC412 on B-chronic lymphocytic leukemia cells in vitro.

Author

Ganeshaguru K, Wickremasinghe RG, Jones DT, Gordon M, Hart SM, Virchis AE, Prentice HG, Hoffbrand AV, Man A, Champain K, Csermak K, and Mehta AB

Subjects
2-Chloroadenosine pharmacology, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Aged, Aged, 80 and over, Apoptosis drug effects, B-Lymphocytes drug effects, B-Lymphocytes enzymology, Calcium Channel Blockers pharmacology, Chlorambucil pharmacology, Deoxyadenosines pharmacology, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Drug Screening Assays, Antitumor, Female, Humans, In Situ Nick-End Labeling, Male, Middle Aged, Palatine Tonsil cytology, Tumor Cells, Cultured drug effects, Tumor Cells, Cultured enzymology, Verapamil pharmacology, Vidarabine analogs & derivatives, Vidarabine pharmacology, 2-Chloroadenosine analogs & derivatives, Antineoplastic Agents pharmacology, Enzyme Inhibitors pharmacology, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Neoplasm Proteins antagonists & inhibitors, Protein Kinase C antagonists & inhibitors, Staurosporine analogs & derivatives, Staurosporine pharmacology
Abstract

Background and Objectives: The staurosporine derivative PKC412 (CGP41251) is a more selective inhibitor of the conventional isoforms of protein kinase C (PKC) than is the parent compound. In addition to its growth inhibitory properties, PKC412 reverses the efflux function of the multidrug resistance (MDR)-1 gene product, P-glycoprotein (P-gp)., Design and Methods: The in vitro actions of PKC412 were investigated in peripheral blood lymphocytes (PBL) from 4 normal volunteers, B-cell isolates from 3 normal tonsils and 31 patients with B-cell chronic lymphocytic leukemia (B-CLL). Following incubation with PKC412 for 2 days, the viability of B-CLL cells was decreased relative to that of controls (63+/-23% at 1 micromole/L; 52+/-30% at 10 micromole/L; n=20). Normal PBL were significantly more resistant to the drug (91+/-5% viable cells at 1 micromole/L; 73+/-18% at 10 micromole/L; n=4). Thirteen of the B-CLL patients were treated with oral PKC412 in a phase II trial., Results: PKC activity in malignant cells from these patients showed a reduction post-treatment of 25-96% of their respective pre-treatment levels. Morphologic analysis, as well as in situ assay for DNA strand breaks (TUNEL assay) showed that B-CLL cells were killed by an apoptotic mechanism. In B-CLL cells the mean IC50, for PKC412, as measured by the reduction of 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), was 2.1 micromol/L in 16 samples in which the IC50 were below the maximum concentration of PKC412 used for the assay. In tonsillar B-cells, the mean IC50 was 11 micromol/L whereas PBL cells were resistant. Four of eight and 1/3 B-CLL samples that were resistant to chlorambucil and fludarabine, respectively, were sensitive to PKC412. In 15/31 B-CLL samples a dose-dependent reversal of P-gp-mediated drug efflux by PKC412 was observed. A statistically significant correlation (p<0.001) was observed between P-gp protein expression as measured by FACScan analysis and the reversal of efflux activity by either PKC412 or verapamil. PKC412 increased the sensitivity of B-CLL cells to 2'-chlorodeoxyadenosine and chlorambucil., Interpretation and Conclusions: This study establishes the in vitro cytotoxic and multidrug resistance (MDR) modulatory properties of PKC412 towards malignant cells from B-CLL patients. The direct antitumor activity combined with the potential for P-gp modulation make PKC412 an attractive drug for the treatment of malignancies expressing the MDR phenotype, or in combination with conventional drugs.

Published
2002

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