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2. Five‐year efficacy and safety of tafasitamab in patients with relapsed or refractory DLBCL: Final results from the Phase II L‐MIND study

Author

Duell, J., primary, Abrisqueta, P., additional, Andre, M., additional, Augustin, M., additional, Gaidano, G., additional, Barca, E. G., additional, Jurczak, W., additional, Kalakonda, N., additional, Liberati, A. M., additional, Maddocks, K. J., additional, Menne, T., additional, Nagy, Z., additional, Tournilhac, O., additional, Bakuli, A., additional, Amin, A., additional, Gurbanov, K., additional, and Salles, G., additional

Published
2023
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3. P1187: END OF TREATMENT 18F FDG-PET/CT RESPONSE IS PROGNOSTIC FOR OVERALL AND PROGRESSION-FREE SURVIVAL IN PERIPHERAL T-CELL LYMPHOMA: RESULTS OF THE UK NCRI PHASE 2 RANDOMISED CHEMO-T TRIAL PET/CT SUBSTUDY

Author

Gleeson, M., primary, Arias, C., additional, Cunningham, D., additional, Peckitt, C., additional, Du, Y., additional, Hujairi, N., additional, To, Y. M., additional, Chen, H.-C., additional, Patel, S., additional, Chau, I., additional, Johnson, P., additional, Ardeshna, K. M., additional, Wotherspoon, A., additional, Attygalle, A., additional, Hawkes, E. A., additional, Macheta, M. P., additional, Collins, G. P., additional, Radford, J., additional, Forbes, A., additional, Hart, A., additional, Montoto, S., additional, McKay, P., additional, Benstead, K., additional, Morley, N., additional, Kalakonda, N., additional, Hasan, Y., additional, Turner, D., additional, and Chua, S., additional

Published
2022
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4. Effect of Prior Therapy and Disease Refractoriness on the Efficacy and Safety of Oral Selinexor in Patients with Diffuse Large B-cell Lymphoma (DLBCL): A Post-hoc Analysis of the SADAL Study

Author

Schuster, M. Zijlstra, J. Casasnovas, R.-O. Vermaat, J.S.P. Kalakonda, N. Goy, A. Choquet, S. Neste, E.V.D. Hill, B. Thieblemont, C. Cavallo, F. De la Cruz, F. Kuruvilla, J. Hamad, N. Jaeger, U. Caimi, P. Gurion, R. Warzocha, K. Bakhshi, S. Sancho, J.-M. Follows, G. Egyed, M. Offner, F. Vassilakopoulos, T. Samal, P. Ku, M. Ma, X. Corona, K. Chamoun, K. Shah, J. Shacham, S. Kauffman, M.G. Canales, M. Maerevoet, M.

Abstract

Background: Despite a number of treatment options, patients with diffuse large B-cell lymphoma (DLBCL) whose disease has become refractory to treatment have a poor prognosis. Selinexor is a novel, oral drug that is approved to treat patients with relapsed/refractory DLBCL. In this post hoc analysis of the SADAL study, a multinational, open-label study, we evaluated subpopulations to determine if response to single agent selinexor is impacted by number of lines of prior treatment, autologous stem cell transplant (ASCT), response to first and most recent therapies, and time to progressive disease. Patients: Patients (n = 134) with DLBCL after 2-5 prior therapies were enrolled in SADAL and received 60mg selinexor twice weekly. Results: The median overall survival was 9.0 months and median progression free survival was 2.6 months. Patients who had the best overall response rate (ORR) and disease control rate were those who had prior ASCT (42.5% and 50.0%) or responded to last line of therapy (35.9% and 43.5%). Patients with primary refractory DLBCL also showed responses (ORR 21.8%). Adverse events between subgroups were similar to the overall study population, the most common being thrombocytopenia (29.1%), fatigue (7.5%), and nausea (6.0%). Conclusion: Regardless of prior therapy and disease refractory status, selinexor treatment demonstrated results consistent with its novel mechanism of action and lack of cross-resistance. Thus, single agent oral selinexor can induce deep, durable, and tolerable responses in patients with DLBCL who have recurrent disease after several chemoimmunotherapy combination regimens. © 2021

Published
2022

5. Diffuse large B cell lymphoma (DLBCL) in patients older than 65 years: analysis of 3 year Real World data of practice patterns and outcomes in England

Author

Hounsome, L., primary, Eyre, T. A., additional, Ireland, R., additional, Hodson, A., additional, Walewska, R., additional, Ardeshna, K., additional, Chaganti, S., additional, McKay, P., additional, Davies, A., additional, Fox, C. P., additional, Kalakonda, N., additional, and Fields, P. A., additional

Published
2021
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6. Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma

Author

Shah, J., Shacham, S., Kauffman, M., Daniele, P., Tomaras, D., Tremblay, G., Casasnovas, R.O., Maerevoet, M., Zijlstra, J., Follows, G., Vermaat, J.S.P., Kalakonda, N., Goy, A.H., Choquet, S., Neste, E. van den, Hill, B.T., Thieblemont, C., Cavallo, F., Cruz, F. de la, Kuruvilla, J., Hamad, N., Bouabdallah, R., Jager, U., Caimi, P., Gurion, R., Warzocha, K., Bakhshi, S., Sancho, J.M., Schuster, M., Egyed, M., Offner, F., Vasilakopoulos, T.P., Samal, P., Nagy, A., Ku, M., and Albendea, M.A.C.

Subjects
health-related quality of life, disutility of adverse events, EQ-5D-5L, diffuse large B-cell lymphoma, health utility, FACT-Lym, patient reported outcomes, health state utility, selinexor
Abstract

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p = 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts.

Published
2021

7. Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma

Author

Shah, J. Shacham, S. Kauffman, M. Daniele, P. Tomaras, D. Tremblay, G. Casasnovas, R.-O. Maerevoet, M. Zijlstra, J. Follows, G. P Vermaat, J.S. Kalakonda, N. Goy, A.H. Choquet, S. Den Neste, E.V. Hill, B.T. Thieblemont, C. Cavallo, F. La Cruz, F.D. Kuruvilla, J. Hamad, N. Bouabdallah, R. Jäger, U. Caimi, P. Gurion, R. Warzocha, K. Bakhshi, S. Sancho, J.M. Schuster, M. Egyed, M. Offner, F. Vasilakopoulos, T.P. Samal, P. Nagy, A. Ku, M. Canales Albendea, M.Á.

Abstract

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT)-Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT-Lymphoma (p ≤ 0.05), FACT-General (p < 0.05) and EuroQoL five-dimensions five-levels index scores (p < 0.001) beginning in cycle 3. The estimated difference in health state utilities for treatment response and progressive disease was both statistically significant and clinically meaningful (mean difference: 0.07; p = 0.001). Conclusion: In patients with relapsed/refractory diffuse large B-cell lymphoma, objective response to selinexor was associated with HRQoL maintenance, reduction in disease-related HRQoL decrements and higher health utilities. © 2021 Patrick Daniele.

Published
2021

8. Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma

Author

Shah, J, Shacham, S, Kauffman, M, Daniele, P, Tomaras, D, Tremblay, G, Casasnovas, RO, Maerevoet, M, Zijlstra, J, Follows, G, Vermaat, JSP, Kalakonda, N, Goy, AH, Choquet, S, Van den Neste, E, Hill, BT, Thieblemont, C, Cavallo, F, de la Cruz, F, Kuruvilla, J, Hamad, N, Bouabdallah, R, Jager, U, Caimi, P, Gurion, R, Warzocha, K, Bakhshi, S, Sancho, JM, Schuster, M, Egyed, M, Offner, F, Vasilakopoulos, TP, Samal, P, Nagy, A, Ku, M, and Albendea, MAC

Subjects
health-related quality of life, disutility of adverse events, EQ-5D-5L, diffuse large B-cell lymphoma, health utility, FACT-Lym, patient reported outcomes, health state utility, selinexor
Abstract

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p = 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts.

Published
2021

9. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study

Author

Hall, Victoria Jane, primary, Foulkes, Sarah, additional, Saei, Ayoub, additional, Andrews, Nick, additional, Oguti, Blanche, additional, Charlett, Andre, additional, Wellington, Edgar, additional, Stowe, Julia, additional, Gillson, Natalie, additional, Atti, Ana, additional, Islam, Jasmin, additional, Karagiannis, Ioannis, additional, Munro, Katie, additional, Khawam, Jameel, additional, Chand, Meera A, additional, Brown, Colin S, additional, Ramsay, Mary, additional, Lopez-Bernal, Jamie, additional, Hopkins, Susan, additional, Andrews, N, additional, Atti, A, additional, Aziz, H, additional, Brooks, T, additional, Brown, CS, additional, Camero, D, additional, Carr, C, additional, Chand, MA, additional, Charlett, A, additional, Crawford, H, additional, Cole, M, additional, Conneely, J, additional, D'Arcangelo, S, additional, Ellis, J, additional, Evans, S, additional, Foulkes, S, additional, Gillson, N, additional, Gopal, R, additional, Hall, L, additional, Hall, VJ, additional, Harrington, P, additional, Hopkins, S, additional, Hewson, J, additional, Hoschler, K, additional, Ironmonger, D, additional, Islam, J, additional, Kall, M, additional, Karagiannis, I, additional, Kay, O, additional, Khawam, J, additional, King, E, additional, Kirwan, P, additional, Kyffin, R, additional, Lackenby, A, additional, Lattimore, M, additional, Linley, E, additional, Lopez-Bernal, J, additional, Mabey, L, additional, McGregor, R, additional, Miah, S, additional, Monk, EJM, additional, Munro, K, additional, Naheed, Z, additional, Nissr, A, additional, O'Connell, AM, additional, Oguti, B, additional, Okafor, H, additional, Organ, S, additional, Osbourne, J, additional, Otter, A, additional, Patel, M, additional, Platt, S, additional, Pople, D, additional, Potts, K, additional, Ramsay, M, additional, Robotham, J, additional, Rokadiya, S, additional, Rowe, C, additional, Saei, A, additional, Sebbage, G, additional, Semper, A, additional, Shrotri, M, additional, Simmons, R, additional, Soriano, A, additional, Staves, P, additional, Taylor, S, additional, Taylor, A, additional, Tengbe, A, additional, Tonge, S, additional, Vusirikala, A, additional, Wallace, S, additional, Wellington, E, additional, Zambon, M, additional, Corrigan, D, additional, Sartaj, M, additional, Cromey, L, additional, Campbell, S, additional, Braithwaite, K, additional, Price, L, additional, Haahr, L, additional, Stewart, S, additional, Lacey, ED, additional, Partridge, L, additional, Stevens, G, additional, Ellis, Y, additional, Hodgson, H, additional, Norman, C, additional, Larru, B, additional, Mcwilliam, S, additional, Roynon, A, additional, Northfield, J, additional, Winchester, S, additional, Cieciwa, P, additional, Pai, A, additional, Bakker, P, additional, Loughrey, C, additional, Watt, A, additional, Adair, F, additional, Hawkins, A, additional, Grant, A, additional, Temple-Purcell, R, additional, Howard, J, additional, Slawson, N, additional, Subudhi, C, additional, Davies, S, additional, Bexley, A, additional, Penn, R, additional, Wong, N, additional, Boyd, G, additional, Rajgopal, A, additional, Arenas-Pinto, A, additional, Matthews, R, additional, Whileman, A, additional, Laugharne, R, additional, Ledger, J, additional, Barnes,, T, additional, Jones, C, additional, Osuji, N, additional, Chitalia, N, additional, Bailey, T, additional, Akhtar, S, additional, Harrison, G, additional, Horne, S, additional, Walker, N, additional, Agwuh, K, additional, Maxwell, V, additional, Graves, J, additional, Williams, S, additional, O'Kelly, A, additional, Ridley, P, additional, Cowley, A, additional, Johnstone, H, additional, Swift, P, additional, Democratis, J, additional, Meda, M, additional, Brake, S, additional, Gunn, J, additional, Selassi, A, additional, Hams, S, additional, Irvine, V, additional, Chandrasekaran, B, additional, Forsyth, C, additional, Radmore, J, additional, Thomas, C, additional, Brown, K, additional, Roberts, S, additional, Burns, P, additional, Gajee, K, additional, Lewis, T, additional, Byrne, TM, additional, Sanderson, F, additional, Knight, S, additional, Macnaughton, E, additional, Burton, BJL, additional, Smith, H, additional, Chaudhuri, R, additional, Aeron-Thomas, J, additional, Hollinshead, K, additional, Shorten, RJ, additional, Swan, A, additional, Favager, C, additional, Murira, J, additional, Baillon, S, additional, Hamer, S, additional, Shah, A, additional, Russell, J, additional, Brennan, D, additional, Dave, A, additional, Chawla, A, additional, Westwell, F, additional, Adeboyeku, D, additional, Papineni, P, additional, Pegg, C, additional, Williams, M, additional, Ahmad, S, additional, Horsley, A, additional, Gabriel, C, additional, Pagget, K, additional, Maloney, G, additional, Ashcroft, J, additional, Del Rosario, I, additional, Crosby-Nwaobi, R, additional, Flanagan, D, additional, Dhasmana, D, additional, Fowler, S, additional, Cameron, E, additional, Prentice, L, additional, Sinclair, C, additional, Bateman, V, additional, McLelland-Brooks, K, additional, Ho, A, additional, Murphy, M, additional, Cochrane, A, additional, Gibson, A, additional, Black, K, additional, Tempeton, K, additional, Donaldson, S, additional, Coke, L, additional, Elumogo, N, additional, Elliott, J, additional, Padgett, D, additional, Cross, A, additional, Mirfenderesky, M, additional, Joyce, S, additional, Sinanovic, I, additional, Howard, M, additional, Cowling, P, additional, Brazil, M, additional, Hanna, E, additional, Abdelrazik, A, additional, Brand, S, additional, Sheridan, EA, additional, Wadams, B, additional, Lloyd, A, additional, Mouland, J, additional, Giles, J, additional, Pottinger, G, additional, Coles, H, additional, Joseph, M, additional, Lee, M, additional, Orr, S, additional, Chenoweth, H, additional, Browne, D, additional, Auckland, C, additional, Lear, R, additional, Mahungu, T, additional, Rodger, A, additional, Warren, S, additional, Brooking, D, additional, Pai, S, additional, Druyeh, R, additional, Smith, E, additional, Stone, S, additional, Meisner, S, additional, Delgado, D, additional, Underhill, E, additional, Keen, L, additional, Aga, M, additional, Domingos, P, additional, Gormley, S, additional, Kerrison, C, additional, Birch, S, additional, DeSilva, T, additional, Allsop, L, additional, Ambalkar, S, additional, Beekes, M, additional, Jose, S, additional, Tomlinson, J, additional, Painter, Sharen, additional, Price, C, additional, Pepperell, J, additional, James, K, additional, Trinick, T, additional, Moore, L, additional, Day, J, additional, Boulos, A, additional, Knox, I, additional, Defever, E, additional, McCracken, D, additional, Gray, K, additional, Houston, A, additional, Planche, T, additional, Pritchard Jones, R, additional, Wycherley, Diane, additional, Bennett, S, additional, Marrs, J, additional, Nimako, K, additional, Stewart, B, additional, Bain, SC, additional, Kalakonda, N, additional, Khanduri, S, additional, Ashby, A, additional, Holden, M, additional, Mahabir, N, additional, Harwood, J, additional, Payne, B, additional, Court, K, additional, White, N, additional, Longfellow, R, additional, Hughes, LE, additional, Green, ME, additional, Halkes, M, additional, Mercer, P, additional, Roebuck, A, additional, Wilson-Davies, E, additional, Gallego, L, additional, Lazarus, R, additional, Aldridge, N, additional, Berry, L, additional, Game, F, additional, Reynolds, T, additional, Holmes, C, additional, Wiselka, M, additional, Higham, A, additional, Booth, M, additional, Duff, C, additional, Alderton, J, additional, Hilton, D, additional, Powell, J, additional, Jackson, A, additional, Plant, AJ, additional, Ahmed, N, additional, Chin, T, additional, Qazzafi, MZ, additional, Moody, AM, additional, Tilley, RE, additional, Donaghy, T, additional, O'Kane, M, additional, Shipman, K, additional, Sierra, R, additional, Parmar, C, additional, Mills, G, additional, Harvey, D, additional, Huang, YWJ, additional, Birch, J, additional, Robinson, L, additional, Board, S, additional, Broadley, A, additional, Laven, C, additional, Todd, N, additional, Eyre, DW, additional, Jeffery, K, additional, Dunachie, S, additional, Duncan, C, additional, Klenerman, P, additional, Turtle, L, additional, Baxendale, H, additional, and Heeney, JL, additional

Published
2021
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10. SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN)

Author

Hall, Victoria Jane, primary, Foulkes, Sarah, additional, Charlett, Andre, additional, Atti, Ana, additional, Monk, Edward J M, additional, Simmons, Ruth, additional, Wellington, Edgar, additional, Cole, Michelle J, additional, Saei, Ayoub, additional, Oguti, Blanche, additional, Munro, Katie, additional, Wallace, Sarah, additional, Kirwan, Peter D, additional, Shrotri, Madhumita, additional, Vusirikala, Amoolya, additional, Rokadiya, Sakib, additional, Kall, Meaghan, additional, Zambon, Maria, additional, Ramsay, Mary, additional, Brooks, Tim, additional, Brown, Colin S, additional, Chand, Meera A, additional, Hopkins, Susan, additional, Andrews, N, additional, Atti, A, additional, Aziz, H, additional, Brooks, T, additional, Brown, CS, additional, Camero, D, additional, Carr, C, additional, Chand, MA, additional, Charlett, A, additional, Crawford, H, additional, Cole, M, additional, Conneely, J, additional, D'Arcangelo, S, additional, Ellis, J, additional, Evans, S, additional, Foulkes, S, additional, Gillson, N, additional, Gopal, R, additional, Hall, L, additional, Hall, VJ, additional, Harrington, P, additional, Hopkins, S, additional, Hewson, J, additional, Hoschler, K, additional, Ironmonger, D, additional, Islam, J, additional, Kall, M, additional, Karagiannis, I, additional, Kay, O, additional, Khawam, J, additional, King, E, additional, Kirwan, P, additional, Kyffin, R, additional, Lackenby, A, additional, Lattimore, M, additional, Linley, E, additional, Lopez-Bernal, J, additional, Mabey, L, additional, McGregor, R, additional, Miah, S, additional, Monk, EJM, additional, Munro, K, additional, Naheed, Z, additional, Nissr, A, additional, O'Connell, AM, additional, Oguti, B, additional, Okafor, H, additional, Organ, S, additional, Osbourne, J, additional, Otter, A, additional, Patel, M, additional, Platt, S, additional, Pople, D, additional, Potts, K, additional, Ramsay, M, additional, Robotham, J, additional, Rokadiya, S, additional, Rowe, C, additional, Saei, A, additional, Sebbage, G, additional, Semper, A, additional, Shrotri, M, additional, Simmons, R, additional, Soriano, A, additional, Staves, P, additional, Taylor, S, additional, Taylor, A, additional, Tengbe, A, additional, Tonge, S, additional, Vusirikala, A, additional, Wallace, S, additional, Wellington, E, additional, Zambon, M, additional, Corrigan, D, additional, Sartaj, M, additional, Cromey, L, additional, Campbell, S, additional, Braithwaite, K, additional, Price, L, additional, Haahr, L, additional, Stewart, S, additional, Lacey, ED, additional, Partridge, L, additional, Stevens, G, additional, Ellis, Y, additional, Hodgson, H, additional, Norman, C, additional, Larru, B, additional, Mcwilliam, S, additional, Winchester, S, additional, Cieciwa, P, additional, Pai, A, additional, Loughrey, C, additional, Watt, A, additional, Adair, F, additional, Hawkins, A, additional, Grant, A, additional, Temple-Purcell, R, additional, Howard, J, additional, Slawson, N, additional, Subudhi, C, additional, Davies, S, additional, Bexley, A, additional, Penn, R, additional, Wong, N, additional, Boyd, G, additional, Rajgopal, A, additional, Arenas-Pinto, A, additional, Matthews, R, additional, Whileman, A, additional, Laugharne, R, additional, Ledger, J, additional, Barnes, T, additional, Jones, C, additional, Botes, D, additional, Chitalia, N, additional, Akhtar, S, additional, Harrison, G, additional, Horne, S, additional, Walker, N, additional, Agwuh, K, additional, Maxwell, V, additional, Graves, J, additional, Williams, S, additional, O'Kelly, A, additional, Ridley, P, additional, Cowley, A, additional, Johnstone, H, additional, Swift, P, additional, Democratis, J, additional, Meda, M, additional, Callens, C, additional, Beazer, S, additional, Hams, S, additional, Irvine, V, additional, Chandrasekaran, B, additional, Forsyth, C, additional, Radmore, J, additional, Thomas, C, additional, Brown, K, additional, Roberts, S, additional, Burns, P, additional, Gajee, K, additional, Byrne, TM, additional, Sanderson, F, additional, Knight, S, additional, Macnaughton, E, additional, Burton, BJL, additional, Smith, H, additional, Chaudhuri, R, additional, Hollinshead, K, additional, Shorten, RJ, additional, Swan, A, additional, Favager, C, additional, Murira, J, additional, Baillon, S, additional, Hamer, S, additional, Gantert, K, additional, Russell, J, additional, Brennan, D, additional, Dave, A, additional, Chawla, A, additional, Westell, F, additional, Adeboyeku, D, additional, Papineni, P, additional, Pegg, C, additional, Williams, M, additional, Ahmad, S, additional, Ingram, S, additional, Gabriel, C, additional, Pagget, K, additional, Maloney, G, additional, Ashcroft, J, additional, Del Rosario, I, additional, Crosby-Nwaobi, R, additional, Reeks, C, additional, Fowler, S, additional, Prentice, L, additional, Spears, M, additional, McKerron, G, additional, McLelland-Brooks, K, additional, Anderson, J, additional, Donaldson, S, additional, Templeton, K, additional, Coke, L, additional, Elumogo, N, additional, Elliott, J, additional, Padgett, D, additional, Mirfenderesky, M, additional, Cross, A, additional, Price, J, additional, Joyce, S, additional, Sinanovic, I, additional, Howard, M, additional, Lewis, T, additional, Cowling, P, additional, Potoczna, D, additional, Brand, S, additional, Sheridan, L, additional, Wadams, B, additional, Lloyd, A, additional, Mouland, J, additional, Giles, J, additional, Pottinger, G, additional, Coles, H, additional, Joseph, M, additional, Lee, M, additional, Orr, S, additional, Chenoweth, H, additional, Auckland, C, additional, Lear, R, additional, Mahungu, T, additional, Rodger, A, additional, Penny-Thomas, K, additional, Pai, S, additional, Zamikula, J, additional, Smith, E, additional, Stone, S, additional, Boldock, E, additional, Howcroft, D, additional, Thompson, C, additional, Aga, M, additional, Domingos, P, additional, Gormley, S, additional, Kerrison, C, additional, Marsh, L, additional, Tazzyman, S, additional, Allsop, L, additional, Ambalkar, S, additional, Beekes, M, additional, Jose, S, additional, Tomlinson, J, additional, Jones, A, additional, Price, C, additional, Pepperell, J, additional, Schultz, M, additional, Day, J, additional, Boulos, A, additional, Defever, E, additional, McCracken, D, additional, Gray, K, additional, Houston, A, additional, Planche, T, additional, Pritchard Jones, R, additional, Wycherley, Diane, additional, Bennett, S, additional, Marrs, J, additional, Nimako, K, additional, Stewart, B, additional, Kalakonda, N, additional, Khanduri, S, additional, Ashby, A, additional, Holden, M, additional, Mahabir, N, additional, Harwood, J, additional, Payne, B, additional, Court, K, additional, Staines, N, additional, Longfellow, R, additional, Green, ME, additional, Hughes, LE, additional, Halkes, M, additional, Mercer, P, additional, Roebuck, A, additional, Wilson-Davies, E, additional, Gallego, L, additional, Lazarus, R, additional, Aldridge, N, additional, Berry, L, additional, Game, F, additional, Reynolds, T, additional, Holmes, C, additional, Wiselka, M, additional, Higham, A, additional, Booth, M, additional, Duff, C, additional, Alderton, J, additional, Jory, H, additional, Virgilio, E, additional, Chin, T, additional, Qazzafi, MZ, additional, Moody, AM, additional, Tilley, R, additional, Donaghy, T, additional, Shipman, K, additional, Sierra, R, additional, Jones, N, additional, Mills, G, additional, Harvey, D, additional, Huang, YWJ, additional, Birch, J, additional, Robinson, L, additional, Board, S, additional, Broadley, A, additional, Laven, C, additional, Todd, N, additional, Eyre, DW, additional, Jeffery, K, additional, Dunachie, S, additional, Duncan, C, additional, Klenerman, P, additional, Turtle, L, additional, De Silva, T, additional, Baxendale, H, additional, and Heeney, JL, additional

Published
2021
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12. Selinexor in patients with relapsed or refractory diffuse large B -cell lymphoma (SADAL): a single -arm, multinational, multicentre, open -label, phase 2 trial

Author

Kalakonda, N., Maerevoet, M., Cavallo, F., Follows, G., Goy, A., Vermaat, J.S.P., Casasnovas, O., Hamad, N., Zijlstra, J.M., Bakhshi, S., Bouabdallah, R., Choquet, S., Gurion, R., Hill, B., Jaeger, U., Sancho, J.M., Schuster, M., Thieblemont, C., Cruz, F. de la, Egyed, M., Mishra, S., Offner, F., Vassilakopoulos, T.P., Warzocha, K., McCarthy, D., Ma, X.W., Corona, K., Saint-Martin, J.R., Chang, H., Landesman, Y., Joshi, A., Wang, H.W., Shah, J., Shacham, S., Kauffman, M., Neste, E. van den, and Canales, M.A.

Abstract

Background Relapsed or refractory diffuse large B -cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single -agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. Methods SADAL was a multicentre, multinational, open -label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B -cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem -cell transplantation were enrolled. Germinal centre B -cell or non -germinal centre B -cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice -weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). Findings Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaining 127 patients received selinexor 60 mg and were included in analyses of primary outcome and safety. The overall response rate was 28% (36/127; 95% CI 20?7-37?0); 15 (12%) achieved a complete response and 21 (17%) a partial response. The most common grade 3-4 adverse events were thrombocytopenia (n=58), neutropenia (n=31), anaemia (n=28), fatigue (n=14), hyponatraemia (n=10), and nausea (n=8). The most common serious adverse events were pyrexia (n=9), pneumonia (n=6), and sepsis (n=6). There were no deaths judged as related to treatment with selinexor. Interpretation Single -drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory DLBCL who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, non-cytotoxic treatment option in this setting.

Published
2020

13. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial

Author

Kalakonda, N. Maerevoet, M. Cavallo, F. Follows, G. Goy, A. Vermaat, J.S.P. Casasnovas, O. Hamad, N. Zijlstra, J.M. Bakhshi, S. Bouabdallah, R. Choquet, S. Gurion, R. Hill, B. Jaeger, U. Sancho, J.M. Schuster, M. Thieblemont, C. De la Cruz, F. Egyed, M. Mishra, S. Offner, F. Vassilakopoulos, T.P. Warzocha, K. McCarthy, D. Ma, X. Corona, K. Saint-Martin, J.-R. Chang, H. Landesman, Y. Joshi, A. Wang, H. Shah, J. Shacham, S. Kauffman, M. Van Den Neste, E. Canales, M.A.

Abstract

Background: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single-agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. Methods: SADAL was a multicentre, multinational, open-label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B-cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem-cell transplantation were enrolled. Germinal centre B-cell or non-germinal centre B-cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice-weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). Findings: Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaining 127 patients received selinexor 60 mg and were included in analyses of primary outcome and safety. The overall response rate was 28% (36/127; 95% CI 20·7–37·0); 15 (12%) achieved a complete response and 21 (17%) a partial response. The most common grade 3–4 adverse events were thrombocytopenia (n=58), neutropenia (n=31), anaemia (n=28), fatigue (n=14), hyponatraemia (n=10), and nausea (n=8). The most common serious adverse events were pyrexia (n=9), pneumonia (n=6), and sepsis (n=6). There were no deaths judged as related to treatment with selinexor. Interpretation: Single-drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory DLBCL who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, non-cytotoxic treatment option in this setting. Funding: Karyopharm Therapeutics Inc. © 2020 Elsevier Ltd

Published
2020

14. HEALTH UTILITY IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (RR-DLBCL) PATIENTS - RESULTS OF A PHASE II TRIAL WITH ORAL SELINEXOR

Author

Casasnovas, RO, Daniele, P, Tremblay, G, Maerevoet, M, Zijlstra, J, Follows, G, Vermaat, JSP, Kalakonda, N, Goy, AH, Choquet, S, Van den Neste, E, Hill, BT, Thieblemont, C, Cavallo, F, de la Cruz, F, Kuruvilla, J, Hamad, N, Bouabdallah, R, Jager, U, Caimi, P, Gurion, R, Warzocha, K, Bakhshi, S, Sancho, JM, Schuster, M, Egyed, M, Offner, F, Vasilakopoulos, T, Samal, P, Nagy, A, Ku, M, and Albendea, MAC

Published
2020

15. Kinobead profiling reveals reprogramming of B-cell receptor signaling in response to therapy within primary CLL cells

Author

Linley, AJ, Griffin, R, Cicconi, S, D’Avola, A, MacEwan, DJ, Pettit, AR, Kalakonda, N, Packham, G, Prior, IA, and Slupsky, JR

Abstract

Induction of signaling via cell surface receptor activation is a critical driver of CLL pathobiology, especially via the B-cell receptor (BCR), which promotes tumor survival and progression. The vital nature of BCR signaling has been recognized through the development of kinase inhibitors (KI), most notably ibrutinib, that target key nodes within this pathway. Current efforts to monitor signaling investigate expression of a highly confined series of kinases and phosphoproteins. While generating key insights, full appreciation of their wider significance to malignant pathology and therapy response remains an unresolved issue. Here, we describe a kinobead-based protocol, used in conjunction with mass-spectrometry (MS) or immunoblotting, to study surface-IgM (sIgM) signaling within primary CLL cells. Employing this approach, we isolated a ‘fingerprint’ of over 30 kinases which displayed unique, patient-specific response to sIgM stimulation, and which displayed greater activation change in CLL cells from patients who had undergone prior chemoimmunotherapy (CIT) compared to those from untreated/treatment-naïve patients. Matched sample analysis of ARCTIC/AdMIRe clinical trial patients revealed the unique nature of the kinome response was present at the intra-patient level, while longitudinal profiling of IcICLLe trial patients supported this as well as showing our finding related to ibrutinib therapy. Refinement of the kinome fingerprint determined 4 kinases linked to proliferation found to be present to a significantly higher level within previously treated patient cells. Proliferation assays confirmed that these patients possess higher proliferative capacity, implying alterations of signaling resulting in promoting of biological processes critical to malignant cells. Collectively, these data represent the first comprehensive investigation into BCR signaling response within CLL, where our probing of kinase active sites reveals unique evidence of adaptive reprogramming in response to therapy. Key points sIgM signaling patterns alter following in vivo therapy using either chemoimmunotherapy or ibrutinib. Kinobeads provide a novel method for high-resolution investigation of signaling in primary CLL cells.

Published
2019
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17. PCN325 Health Utility in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (RR-DLBCL) Patients - Results of a Phase II Trial with ORAL Selinexor

Author

Casasnovas, R.O., primary, Daniele, P., additional, Tremblay, G., additional, Maerevoet, M., additional, Zijlstra, J., additional, Follows, G., additional, Vermaat, J.S.P., additional, Kalakonda, N., additional, Goy, A.H., additional, Choquet, S., additional, Van Den Neste, E., additional, Hill, B.T., additional, Thieblemont, C., additional, Cavallo, F., additional, de la Cruz, F., additional, Kuruvilla, J., additional, Hamad, N., additional, Bouabdallah, R., additional, Jäger, U., additional, Caimi, P., additional, Gurion, R., additional, Warzocha, K., additional, Bakhshi, S., additional, Sancho, J.M., additional, Schuster, M., additional, Egyed, M., additional, Offner, F., additional, Vasilakopoulos, T., additional, Samal, P., additional, Nagy, A., additional, Ku, M., additional, and Canales Albendea, M.Á., additional

Published
2020
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18. Kinobead Profiling Reveals Reprogramming of B-cell Receptor Signaling in Response to Therapy Within Primary Chronic Lymphocytic Leukemia Cells

Author

Linley, AJ, primary, Karydis, LI, additional, Mondru, A, additional, D’Avola, A, additional, Cicconi, S, additional, Griffin, R, additional, Forconi, F, additional, Pettitt, AR, additional, Kalakonda, N, additional, Rawstron, A, additional, Hillmen, P, additional, Steele, AJ, additional, MacEwan, DJ, additional, Packham, G, additional, Prior, IA, additional, and Slupsky, JR, additional

Published
2019
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21. CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial

Author

Gleeson, M., Peckitt, C., To, Y.M., Edwards, L., Oates, J., Wotherspoon, A., Attygalle, A.D., Zerizer, I., Sharma, B., Chua, S., Begum, R., Chau, I., Johnson, P., Ardeshna, K.M., Hawkes, E.A., Macheta, M.P., Collins, G.P., Radford, J., Forbes, A., Hart, A., Montoto, S., McKay, P., Benstead, K., Morley, N., Kalakonda, N., Hasan, Y., Turner, D., and Cunningham, D.

Subjects
Aged, 80 and over, Male, Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, Lymphoma, T-Cell, Peripheral, Middle Aged, Deoxycytidine, Methylprednisolone, Gemcitabine, Article, Doxorubicin, Vincristine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Humans, Prednisone, Female, Cisplatin, Cyclophosphamide, Aged
Abstract

Background: Outcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients. Methods: We did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0–3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1–5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m2 on days 1, 8, and 15, cisplatin 100 mg/m2 on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1–5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18). Findings: Between June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6–38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21–1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections. Interpretation: The number of patients with a complete response or unconfirmed complete response did not differ between the groups, indicating that GEM-P was not superior for this outcome. CHOP should therefore remain the reference regimen for previously untreated peripheral T-cell lymphoma. Funding: Bloodwise and the UK National Institute of Health Research.

Published
2018

22. SAFETY AND EFFICACY OF THE PD-L1 INHIBITOR DURVALUMAB WITH R-CHOP OR R2 -CHOP IN SUBJECTS WITH PREVIOUSLY UNTREATED, HIGH-RISK DLBCL

Author

Nowakowski, G., primary, Willenbacher, W., additional, Greil, R., additional, Larsen, T.S., additional, Patel, K., additional, Jäger, U., additional, Manges, R.F., additional, Trümper, L., additional, Haioun, C., additional, Everaus, H., additional, Kalakonda, N., additional, Knoble, J., additional, de Nully Brown, P., additional, Jørgensen, J.M., additional, Cunningham, D., additional, Domper Rubio, N., additional, Casadebaig, M., additional, Manzke, O., additional, and Munoz, J., additional

Published
2019
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23. BRIEF CO-ADMINISTRATION OF IDELALISIB MAY IMPROVE THE LONG-TERM EFFICACY OF FRONTLINE CHEMOIMMUNOTHERAPY IN CHRONIC LYMPHOCYTIC LEUKAEMIA: 3-YEAR FOLLOW-UP FROM THE RIALTO TRIAL

Author

Pettitt, A., primary, Kalakonda, N., additional, Cicconi, S., additional, Murphy, C., additional, Menon, G., additional, Coupland, S.E., additional, Oates, M., additional, Lin, K., additional, Pocock, C., additional, Jenkins, S., additional, Schuh, A., additional, Wandroo, F., additional, Rassam, S., additional, Duncombe, A.S., additional, Cervi, P., additional, Paneesha, S., additional, Aldouri, M., additional, Fox, C., additional, Knechtli, C., additional, Hamblin, M., additional, Turner, D., additional, and Hillmen, P., additional

Published
2019
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25. NCRI PETREA TRIAL: A PHASE 3 EVALUATION OF PET-GUIDED, RESPONSE-ADAPTED THERAPY IN PATIENTS WITH PREVIOUSLY UNTREATED, ADVANCED-STAGE, HIGH-TUMOUR-BURDEN FOLLICULAR LYMPHOMA

Author

Pettitt, A.R., primary, Barrington, S., additional, Kalakonda, N., additional, Khan, U.T., additional, Jackson, R., additional, Carruthers, S., additional, Oates, M., additional, Lin, K., additional, Ardeshna, K., additional, Eyre, T., additional, Fox, C.P., additional, Kennedy, B., additional, Linton, K., additional, Malladi, R., additional, Menne, T., additional, Okosun, J., additional, Paneesha, S., additional, Rule, S., additional, Johnston, A., additional, and Trotman, J., additional

Published
2019
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26. EXPLORATORY BIOMARKER ANALYSIS IN THE PH 3 ECHELON-1 STUDY: WORSE OUTCOME WITH ABVD IN PATIENTS WITH ELEVATED BASELINE LEVELS OF SCD30 AND TARC

Author

Radford, J., primary, Connors, J.M., additional, Younes, A., additional, Gallamini, A., additional, Ansell, S.M., additional, Kim, W.S., additional, Cheong, J., additional, Flinn, I., additional, Kalakonda, N., additional, Kaminski, M., additional, Pettengell, R., additional, Onsum, M., additional, Josephson, N., additional, Kuroda, S., additional, Liu, R., additional, Miao, H., additional, Gautam, A., additional, Trepicchio, W.L., additional, and Sureda, A., additional

Published
2019
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28. PRIMARY ANALYSIS RESULTS OF THE SINGLE-ARM PHASE II STUDY OF MOR208 PLUS LENALIDOMIDE IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (L-MIND)

Author

Salles, G., primary, Duell, J., additional, González Barca, E., additional, Jurczak, W., additional, Liberati, A.M., additional, Nagy, Z., additional, Obr, A., additional, Gaidano, G., additional, Andre, M., additional, Kalakonda, N., additional, Dreyling, M., additional, Zinzani, P.L., additional, Dirnberger-Hertweck, M., additional, Weirather, J., additional, Ambarkhane, S., additional, and Maddocks, K., additional

Published
2019
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29. PF296 UPDATE OF THE SINGLE-ARM PHASE II L-MIND STUDY OF MOR208 PLUS LENALIDOMIDE IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: HIGH OVERALL RESPONSE RATES IN PATIENT SUBGROUPS WITH POOR PROGNOSIS

Author

Duell, J., primary, Maddocks, K., additional, González Barca, E., additional, Jurczak, W., additional, Liberati, A.M., additional, Nagy, Z., additional, Obr, A., additional, Gaidano, G., additional, André, M., additional, Kalakonda, N., additional, Dreyling, M., additional, Zinzani, P.L., additional, Dirnberger-Hertweck, M., additional, Weirather, J., additional, Ambarkhane, S., additional, and Salles, G., additional

Published
2019
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30. A PHASE 2B STUDY OF SELINEXOR IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)

Author

Kalakonda, N., primary, Cavallo, F., additional, Follows, G., additional, Goy, A., additional, Vermaat, J., additional, Casasnovas, O., additional, Lavee, O., additional, Maerevoet, M., additional, Zijlstra, J., additional, Bakshi, S., additional, Bouabdallah, R., additional, Choquet, S., additional, Gurion, R., additional, Hill, B., additional, Jaeger, U., additional, Sancho, J., additional, Schuster, M., additional, Thieblemont, C., additional, De la Cruz, F., additional, Egyed, M., additional, Mishra, S., additional, Offner, F., additional, Vassilakopoulos, T., additional, Warzocha, K., additional, Oluyadi, A., additional, McCarthy, D., additional, Ma, X., additional, Corona, K., additional, Shah, J., additional, Van Den Neste, E., additional, and Canales, M., additional

Published
2019
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31. CREATION OF ISOGENIC CELL LINE MODELS OF 17P DELETION TO STUDY CLONAL EVOLUTION AND MECHANISMS OF THERAPY RESISTANCE IN CLL AND DLBCL.

Author

van Kampen, F. L., Glenn, M., Pettitt, A., Kalakonda, N., and Slupsky, J.

Subjects
CELL lines, CHRONIC lymphocytic leukemia, DIFFUSE large B-cell lymphomas, B cell lymphoma, CD19 antigen
Abstract

B Introduction: b A deletion of chromosome 17p (del17p), on which the tumour suppressor gene I TP53 i is located, is a prevalent genetic aberration in many cancer types. B Results: b Isogenic HCT116 cell lines with hemizygous and homozygous I TP53 i deletion, as well as hemizygous 17p deletion were obtained (Figure 1). [Extracted from the article]

Published
2023
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33. L-MIND: MOR208 COMBINED WITH LENALIDOMIDE (LEN) IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (R-R DLBCL) - A SINGLE-ARM PHASE II STUDY

Author

Salles, G., primary, González Barca, E., additional, Jurczak, W., additional, Liberati, A.M., additional, Duell, J., additional, Nagy, Z., additional, Papajík, T., additional, Andre, M., additional, Kalakonda, N., additional, Dreyling, M., additional, Zinzani, P.L., additional, Ambarkhane, S., additional, Weirather, J., additional, and Maddocks, K., additional

Published
2017
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34. CHOP VERSUS GEM-P IN THE FIRST-LINE TREATMENT OF T-CELL LYMPHOMA (PTCL): INITIAL RESULTS OF THE UK NRCI PHASE II RANDOMISED CHEMO-T TRIAL

Author

Gleeson, M., primary, Peckitt, C., additional, To, Y.M., additional, Edwards, L., additional, Chau, I., additional, Johnson, P., additional, Ardeshna, K.M., additional, Wotherspoon, A., additional, Attygalle, A., additional, Begum, R., additional, Chua, S., additional, Zerizer, I., additional, Hawkes, E.A., additional, Macheta, M.P., additional, Collins, G.P., additional, Radford, J.A., additional, Forbes, A., additional, Hart, A., additional, Montoto, S., additional, McKay, P., additional, Benstead, K., additional, Morley, N., additional, Kalakonda, N., additional, Hasan, Y., additional, Turner, D., additional, and Cunningham, D., additional

Published
2017
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35. THE ROLE OF 18F FDG-PET/CT IN PERIPHERAL T-CELL LYMPHOMA (PTCL): INITIAL RESULTS OF THE UK NCRI MULTICENTRE PHASE II RANDOMISED CHEMO-T TRIAL PET/CT SUBSTUDY

Author

Gleeson, M., primary, Peckitt, C., additional, Cunningham, D., additional, To, Y.M., additional, Edwards, L., additional, Chau, I., additional, Johnson, P., additional, Ardeshna, K.M., additional, Wotherspoon, A., additional, Attygalle, A., additional, Begum, R., additional, Zerizer, I., additional, Hawkes, E.A., additional, Macheta, M.P., additional, Collins, G.P., additional, Radford, J.A., additional, Forbes, A., additional, Hart, A., additional, Montoto, S., additional, McKay, P., additional, Benstead, K., additional, Morley, N., additional, Kalakonda, N., additional, Hasan, Y., additional, Turner, D., additional, and Chua, S., additional

Published
2017
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36. EFFECT OF ADDING IDELALISIB TO FRONTLINE OFATUMUMAB PLUS EITHER CHLORAMBUCIL OR BENDAMUSTINE IN LESS FIT PATIENTS WITH CLL: PRELIMINARY RESULTS FROM THE NCRI RIALTO TRIAL.

Author

Pettitt, A.R., primary, Kalakonda, N., additional, Polydoros, F., additional, Bickerstaff, M., additional, Menon, G., additional, Coupland, S.E., additional, Oates, M., additional, Lin, K., additional, Pocock, C., additional, Jenkins, S., additional, Schuh, A., additional, Wandroo, F., additional, Rassam, S., additional, Duncombe, A.S., additional, Jenner, M., additional, Cervi, P., additional, Paneesha, S., additional, Aldouri, M., additional, Fox, C.P., additional, Knechtli, C., additional, Hamblin, M., additional, Turner, D., additional, and Hillmen, P., additional

Published
2017
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40. research paper Systemic AL amyloidosis due to non-Hodgkin's lymphoma: an unusual clinicopathologic association.

Author

Cohen, A.D., Zhou, P., Xiao, Q., Fleisher, M., kalakonda, N., Akhurst, T., Chitale, D.A., Moscowitz, C., Dhodapkar, M.V., Teruya-Feldstein, J., Filippa, D., and Comenzo, R.L.

Subjects
AMYLOIDOSIS, LYMPHOMAS, PLASMA cells, PROTEIN metabolism disorders, IMMUNOGLOBULINS, RITUXIMAB
Abstract

Systemic AL amyloidosis (AL) is a disorder in which light chains form fibrillar deposits, leading to organ dysfunction and death. Rarely, AL has been associated with non-Hodgkin's lymphoma (NHL), although this association has not been well characterized. We report a series of six patients with AL associated with NHL, primarily lymphoplasmacytic lymphoma. Organ involvement was variable, with frequent bulky lymphadenopathy and visceral cavity deposits, but no cardiac involvement. Positron emission tomography scans were negative. Bone marrow and lymph node biopsies showed a mixed population of CD20+ lymphoid and CD138+ plasma cells. Serum free light chains were elevated, and correlated with response to therapy. Immunoglobulin light chain variable region (Ig VL) germline gene use was typical for AL, reflecting previously observed correlations between germline gene use and organ tropism. Five patients received rituximab-based therapies with two responses. Two patients underwent autologous stem cell transplantation with one complete haematological response. Four patients survive at 10–132 months from diagnosis. AL with NHL has distinctive clinical features but employs the same Ig VL gene repertoire as AL with clonal plasma cell dyscrasias. Serial serum free light chain levels are useful for tracking response to therapy. Treatments aimed at both lymphoid and plasma cell components appear warranted. [ABSTRACT FROM AUTHOR]

Published
2004
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41. Transcriptional mechanism of vascular endothelial growth factor-induced expression of protein kinase CβII in chronic lymphocytic leukaemia cells

Author

Al-Sanabra O, Ad, Duckworth, Ma, Glenn, Br, Brown, Angelillo P, Lee K, Herbert J, Falciani F, Kalakonda N, and Joseph Slupsky

Subjects
STAT3 Transcription Factor, Transcriptional Activation, Vascular Endothelial Growth Factor A, B-Lymphocytes, Sp1 Transcription Factor, hemic and lymphatic diseases, Protein Kinase C beta, Humans, Promoter Regions, Genetic, Leukemia, Lymphocytic, Chronic, B-Cell, Article, Protein Binding, Signal Transduction
Abstract

A key feature of chronic lymphocytic leukaemia (CLL) cells is overexpressed protein kinase CβII (PKCβII), an S/T kinase important in the pathogenesis of this and other B cell malignancies. The mechanisms contributing to enhanced transcription of the gene coding for PKCβII, PRKCB, in CLL cells remain poorly described, but could be important because of potential insight into how the phenotype of these cells is regulated. Here, we show that SP1 is the major driver of PKCβII expression in CLL cells where enhanced association of this transcription factor with the PRKCB promoter is likely because of the presence of histone marks permissive of gene activation. We also show how vascular endothelial growth factor (VEGF) regulates PRKCB promoter function in CLL cells, stimulating PKCβ gene transcription via increased association of SP1 and decreased association of STAT3. Taken together, these results are the first to demonstrate a clear role for SP1 in the up regulation of PKCβII expression in CLL cells, and the first to link SP1 with the pathogenesis of this and potentially other B cell malignancies where PKCβII is overexpressed.

42. Understanding the relevance of epigenetic reprogramming for resistance to HDAC inhibitors in cancer cells

Author

Perikala, V., Kalakonda, N., and Slupsky, J.

Subjects
616.99
Abstract

Therapeutic responses to Histone deacetylase (HDAC) inhibitors (HDACi) in many cancers are well described but development of resistance to HDACi is a major stumbling block. Whether HDACis induce epigenetic reprogramming and how this contributes to relapse is not reported. A CTCL cell line HuT78, and a CLL cell line MEC1, were used to develop HDACi resistant clones (RHuT78 and RMEC1 respectively) that persistently grow in the presence of the clinically used HDAC inhibitor Romidepsin. RHuT78 cells show perturbed trimethylation of histone H3 lysine K4 on Romidepsin treatment which linked to higher protein expression levels of the implicated demethylase KDM5A. Following on from these experiments, a qRT-PCR epigenetic gene expression array was used to quantify levels of 84 epigenetic gene transcripts in RHuT78 cells and significantly altered genes were taken forward for further investigation. Studies of gene expression patterns in parental, resistant and ‘drug holiday’ cell lines of both HuT78 and MEC1 led to particular interest in HDAC8, DNMT3A and DNMT3B. Functional studies showed that HDAC8 overexpression increased proliferation and resistance of HuT78 cells to Romidepsin. Parallel observations suggested an increase in proliferation of resistant cell lines cultured in the presence of the HDACi. This increased proliferation was seen even with lower concentrations of Romidepsin and argues against prolonged monotherapy using HDACis. Significantly, inhibitors of DNA methyltransferases synergised with Romidepsin in a dose and schedule dependent manner, reversing the changes in epigenetic gene expression associated with resistance and causing increased apoptosis in RHuT78 cells. Taken together this thesis identifies and characterises an unacknowledged contribution of epigenetic reprogramming to drug resistance and provides insights into the effects of Romidepsin on the epigenome that could potentially contribute to HDACi resistance.

Published
2016
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43. UNDERSTANDING THE RELEVANCE OF EPIGENETIC REPROGRAMMING FOR RESISTANCE TO HDAC INHIBITORS IN CANCER CELLS

Author

Perikala, V, kalakonda, N, and slupsky, J

Abstract

Therapeutic responses to Histone deacetylase (HDAC) inhibitors (HDACi) in many cancers are well described but development of resistance to HDACi is a major stumbling block. Whether HDACis induce epigenetic reprogramming and how this contributes to relapse is not reported. A CTCL cell line HuT78, and a CLL cell line MEC1, were used to develop HDACi resistant clones (RHuT78 and RMEC1 respectively) that persistently grow in the presence of the clinically used HDAC inhibitor Romidepsin. RHuT78 cells show perturbed trimethylation of histone H3 lysine K4 on Romidepsin treatment which linked to higher protein expression levels of the implicated demethylase KDM5A. Following on from these experiments, a qRT-PCR epigenetic gene expression array was used to quantify levels of 84 epigenetic gene transcripts in RHuT78 cells and significantly altered genes were taken forward for further investigation. Studies of gene expression patterns in parental, resistant and ‘drug holiday’ cell lines of both HuT78 and MEC1 led to particular interest in HDAC8, DNMT3A and DNMT3B. Functional studies showed that HDAC8 overexpression increased proliferation and resistance of HuT78 cells to Romidepsin. Parallel observations suggested an increase in proliferation of resistant cell lines cultured in the presence of the HDACi. This increased proliferation was seen even with lower concentrations of Romidepsin and argues against prolonged monotherapy using HDACis. Significantly, inhibitors of DNA methyltransferases synergised with Romidepsin in a dose and schedule dependent manner, reversing the changes in epigenetic gene expression associated with resistance and causing increased apoptosis in RHuT78 cells. Taken together this thesis identifies and characterises an unacknowledged contribution of epigenetic reprogramming to drug resistance and provides insights into the effects of Romidepsin on the epigenome that could potentially contribute to HDACi resistance.

45. Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety findings in the phase II L-MIND study.

Author

Duell J, Abrisqueta P, Andre M, Gaidano G, Gonzales-Barca E, Jurczak W, Kalakonda N, Liberati AM, Maddocks KJ, Menne T, Nagy Z, Tournilhac O, Kuffer C, Bakuli A, Amin A, Gurbanov K, and Salles G

Subjects
Humans, Lenalidomide therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse pathology
Abstract

Tafasitamab, an anti-CD19 immunotherapy, is used with lenalidomide for patients with autologous stem cell transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma based on the results of the phase II L-MIND study (NCT02399085). We report the final 5-year analysis of this study. Eighty patients ≥18 years who had received one to three prior systemic therapies, and had Eastern Cooperative Oncology Group performance status 0-2 received up to 12 cycles of co-administered tafasitamab and lenalidomide, followed by tafasitamab monotherapy until disease progression or unacceptable toxicity. The primary endpoint was the best objective response rate. Secondary endpoints included duration of response, progression-free survival, overall survival, and safety. Exploratory analyses evaluated efficacy endpoints by prior lines of therapy. At data cutoff on November 14, 2022, the objective response rate was 57.5%, with a complete response rate of 41.3% (n=33), which was consistent with prior analyses. With a median follow-up of 44.0 months, the median duration of response was not reached. The median progression-free survival was 11.6 months (95% confidence interval [95% CI]: 5.7-45.7) with a median follow-up of 45.6 months. The median overall survival was 33.5 months (95% CI: 18.3-not reached) with a median follow-up of 65.6 months. Patients who had received one prior line of therapy (n=40) showed a higher objective response rate (67.5%; 52.5% complete responses) compared to patients who had received two or more prior lines of therapy (n=40; 47.5%; 30% complete responses), but the median duration of response was not reached in either subgroup. Other exploratory analyses revealed consistent long-term efficacy results across subgroups. Adverse events were consistent with those described in previous reports, were manageable, and their frequency decreased during tafasitamab monotherapy, with no new safety concerns. This final 5-year analysis of L-MIND demonstrates that the immunotherapy combination of tafasitamab and lenalidomide is well tolerated and has long-term clinical benefit with durable responses.

Published
2024
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46. Highly Multiplexed and Simultaneous Characterization of Protein and RNA in Single Cells by Flow or Mass Cytometry Platforms Using Proximity Ligation Assay for RNA.

Author

Duckworth AD, Slupsky JR, and Kalakonda N

Subjects
In Situ Hybridization, Oligonucleotide Probes, Staining and Labeling, Antibodies, RNA genetics
Abstract

In situ hybridization of oligonucleotide probes to intracellular RNA allows quantification of predefined gene transcripts within millions of single cells using cytometry platforms. Previous methods have been hindered by the number of RNA that can be analyzed simultaneously. Here we describe a method called proximity ligation assay for RNA (PLAYR) that permits highly multiplexed RNA analysis that can be combined with antibody staining. Potentially any number of RNA combined with antigen can be analyzed together, being limited only by the number of analytes that can be measured simultaneously., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
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48. PKCβ Facilitates Leukemogenesis in Chronic Lymphocytic Leukaemia by Promoting Constitutive BCR-Mediated Signalling.

Author

Hay J, Tarafdar A, Holroyd AK, Moka HA, Dunn KM, Alshayeb A, Lloyd BH, Cassels J, Malik N, Khan AF, Sou I, Lees J, Almuhanna HNB, Kalakonda N, Slupsky JR, and Michie AM

Abstract

B cell antigen receptor (BCR) signalling competence is critical for the pathogenesis of chronic lymphocytic leukaemia (CLL). Defining key proteins that facilitate these networks aid in the identification of targets for therapeutic exploitation. We previously demonstrated that reduced PKCα function in mouse hematopoietic stem/progenitor cells (HPSCs) resulted in PKCβII upregulation and generation of a poor-prognostic CLL-like disease. Here, prkcb knockdown in HSPCs leads to reduced survival of PKCα-KR-expressing CLL-like cells, concurrent with reduced expression of the leukemic markers CD5 and CD23. SP1 promotes elevated expression of prkcb in PKCα-KR expressing cells enabling leukemogenesis. Global gene analysis revealed an upregulation of genes associated with B cell activation in PKCα-KR expressing cells, coincident with upregulation of PKCβII: supported by activation of key signalling hubs proximal to the BCR and elevated proliferation. Ibrutinib (BTK inhibitor) or enzastaurin (PKCβII inhibitor) treatment of PKCα-KR expressing cells and primary CLL cells showed similar patterns of Akt/mTOR pathway inhibition, supporting the role for PKCβII in maintaining proliferative signals in our CLL mouse model. Ibrutinib or enzastaurin treatment also reduced PKCα-KR-CLL cell migration towards CXCL12. Overall, we demonstrate that PKCβ expression facilitates leukemogenesis and identify that BCR-mediated signalling is a key driver of CLL development in the PKCα-KR model.

Published
2022
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49. Effect of Prior Therapy and Disease Refractoriness on the Efficacy and Safety of Oral Selinexor in Patients with Diffuse Large B-cell Lymphoma (DLBCL): A Post-hoc Analysis of the SADAL Study.

Author

Schuster M, Zijlstra J, Casasnovas RO, Vermaat JSP, Kalakonda N, Goy A, Choquet S, Neste EVD, Hill B, Thieblemont C, Cavallo F, De la Cruz F, Kuruvilla J, Hamad N, Jaeger U, Caimi P, Gurion R, Warzocha K, Bakhshi S, Sancho JM, Follows G, Egyed M, Offner F, Vassilakopoulos T, Samal P, Ku M, Ma X, Corona K, Chamoun K, Shah J, Shacham S, Kauffman MG, Canales M, and Maerevoet M

Subjects
Humans, Hydrazines adverse effects, Triazoles adverse effects, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Non-Hodgkin drug therapy
Abstract

Background: Despite a number of treatment options, patients with diffuse large B-cell lymphoma (DLBCL) whose disease has become refractory to treatment have a poor prognosis. Selinexor is a novel, oral drug that is approved to treat patients with relapsed/refractory DLBCL. In this post hoc analysis of the SADAL study, a multinational, open-label study, we evaluated subpopulations to determine if response to single agent selinexor is impacted by number of lines of prior treatment, autologous stem cell transplant (ASCT), response to first and most recent therapies, and time to progressive disease., Patients: Patients (n = 134) with DLBCL after 2-5 prior therapies were enrolled in SADAL and received 60mg selinexor twice weekly., Results: The median overall survival was 9.0 months and median progression free survival was 2.6 months. Patients who had the best overall response rate (ORR) and disease control rate were those who had prior ASCT (42.5% and 50.0%) or responded to last line of therapy (35.9% and 43.5%). Patients with primary refractory DLBCL also showed responses (ORR 21.8%). Adverse events between subgroups were similar to the overall study population, the most common being thrombocytopenia (29.1%), fatigue (7.5%), and nausea (6.0%)., Conclusion: Regardless of prior therapy and disease refractory status, selinexor treatment demonstrated results consistent with its novel mechanism of action and lack of cross-resistance. Thus, single agent oral selinexor can induce deep, durable, and tolerable responses in patients with DLBCL who have recurrent disease after several chemoimmunotherapy combination regimens., (Copyright © 2021. Published by Elsevier Inc.)

Published
2022
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50. COVID-19 outcomes in haematopoietic cell transplant recipients: A systematic review and meta-analysis.

Author

Lim YJ, Khan U, Karpha I, Ross A, Saif M, Remberger M, Kalakonda N, Pettitt AR, and Floisand Y

Abstract

Up-to-date information on coronavirus disease 2019 (COVID-19) outcomes and risk factors in haematopoietic cell transplantation (HCT) recipients is required to inform on decisions about cancer treatment and COVID-19 mitigation strategies. We performed a meta-analysis to address this knowledge gap. All studies with at least five patients who reported COVID-19-related deaths in HCT recipients were included. The primary outcome was COVID-19-related death. Secondary outcomes were COVID-19-related mechanical ventilation (MV) and intensive care unit (ITU) admission. The cumulative COVID-19-related death rate among HCT recipients was 21% (95% confidence interval [CI] 18%-24%), while MV and ITU admission rates were 14% (95% CI 11%-17%) and 18% (95% CI 14%-22%), respectively. Subgroup analysis showed higher death rates in patients who developed COVID-19 within 12 months of HCT (risk ratio [RR] 1.82, 95% CI 1.09-3.03), within 6 months of receiving immunosuppressant drugs (RR 2.11, 95% CI 1.38-3.20) or in the context of active graft-versus-host disease (RR 2.38, 95% CI 1.10-5.16). Our findings support the idea that HCT should remain an integral part of cancer treatment during the COVID-19 pandemic but also highlight the need to prioritise preventative measures in those patients who are at increased risk of adverse COVID-19 outcomes., Competing Interests: Andrew Ross, Indrani Karpha, Muhammad Saif and Yngvar Floisand are employed by Clatterbridge Cancer Centre NHS Foundation Trust. Yeong Jer Lim, Andrew R. Pettitt and Nagesh Kalakonda are employed by the University of Liverpool. Yeong Jer Lim is supported by the NW MRC fellowship scheme (award number MR/N025989/1). Mats Remberger is employed by Uppsala University Hospital, Sweden and supported by grants from the Swedish Research Council (VR 2017‐00355)., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Published
2022
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