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44 results on '"Garcia Sanz, R."'

1. The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression

Author: Medina-Herrera, A., Vazquez, I., Cuenca, I., Rosa-Rosa, J. M., Ariceta, B., Jimenez, C., Fernandez-Mercado, M., Larrayoz, M. J., Gutierrez, N. C., Fernandez-Guijarro, M., Gonzalez-Calle, V., Rodriguez-Otero, P., Oriol, A., Rosiñol, L., Alegre, A., Escalante, F., De La Rubia, J., Teruel, A. I., De Arriba, F., Hernandez, M. T., Lopez-Jimenez, J., Ocio, E. M., Puig, N., Paiva, B., Lahuerta, J. J., Bladé, J., San Miguel, J. F., Mateos, M. V., Martinez-Lopez, J., Calasanz, M. J., and Garcia-Sanz, R.
Published: 2024
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2. Health-related quality of life in patients with Waldenström macroglobulinemia: results from the ASPEN trial.

Author: Tedeschi, A, Tam, CS, Owen, RG, Buske, C, Leblond, V, Dimopoulos, M, Garcia-Sanz, R, Castillo, JJ, Trotman, J, Treon, SP, Yang, K, Tang, B, Allewelt, H, Patel, S, Chan, WY, Cohen, A, Chen, S, Barnes, G, Tedeschi, A, Tam, CS, Owen, RG, Buske, C, Leblond, V, Dimopoulos, M, Garcia-Sanz, R, Castillo, JJ, Trotman, J, Treon, SP, Yang, K, Tang, B, Allewelt, H, Patel, S, Chan, WY, Cohen, A, Chen, S, and Barnes, G
Abstract: Aim ASPEN is a randomized, open-label, Phase III study comparing zanubrutinib and ibrutinib in patients with Waldenström macroglobulinemia (WM). Materials & methods: Patient-reported outcomes were exploratory end points assessed using the EORTC QLQ-C30 and EQ-5D-5L VAS scores. Results: Overall, 201 patients (102 zanubrutinib; 99 ibrutinib) were enrolled. Clinically meaningful differences were observed in diarrhea and nausea/vomiting in both the intent-to-treat population and in patients attaining very good partial response (VGPR) in earlier cycles of treatment, as well as in long-term physical functioning and fatigue in patients achieving VGPR. Conclusion: Treatment with zanubrutinib was associated with greater improvements in health-related quality of life compared with ibrutinib in patients with WM and MYD88 mutations.Clinical Trial Registration: NCT03053440 (ClinicalTrials.gov).
Published: 2024

3. Decoding the historical tale: COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022

Author: Salmanton-Garcia, J., Marchesi, F., Farina, F., Weinbergerova, B., Itri, F., Davila-Valls, J., Martin-Perez, S., Glenthoj, A., Hersby, D. S., Gomes da Silva, M., Nunes Rodrigues, R., Lopez-Garcia, A., Cordoba, R., Bilgin, Y. M., Falces-Romero, I., El-Ashwah, S., Emarah, Z., Besson, C., Kohn, M., Van Doesum, J., Ammatuna, E., Marchetti, M., Labrador, J., Zambrotta, G. P. M., Verga, L., Jaksic, O., Nucci, M., Piukovics, K., Cabirta-Touzon, A., Jimenez, M., Arellano, E., Espigado, I., Blennow, O., Nordlander, A., Meers, S., van Praet, J., Aiello, T. F., Garcia-Vidal, C., Fracchiolla, N., Sciume, M., Seval, G. C., Zak, P., Buquicchio, C., Tascini, C., Grafe, S. K., Schonlein, M., Adzic-Vukicevic, T., Bonuomo, V., Cattaneo, C., Nizamuddin, S., Cernan, M., Plantefeve, G., Prin, R., Szotkovski, T., Collins, G. P., Dargenio, M., Petzer, V., Wolf, D., Colovic, N., Prezioso, L., Valkovic, T., Passamonti, F., Mendez, G. -A., Sili, U., Vena, A., Bavastro, M., Limongelli, A., Duarte, R. F., Ledoux, M. -P., Cvetanoski, M., Stojanoski, Z., Machado, M., Batinic, J., Magliano, G., Biernat, M. M., Pantic, N., Poulsen, C. B., Cuccaro, A., Del Principe, M. I., Kulasekararaj, A., Ormazabal-Velez, I., Busca, A., Demirkan, F., Ijaz, M., Klimko, N., Stoma, I., Khostelidi, S., Fernandez, N., Omrani, A. S., Bergantim, R., De Jonge, N., Fouquet, G., Navratil, M., Abu-Zeinah, G., Samarkos, M., Maertens, J., De Ramon, C., Guidetti, A., Magyari, F., Gonzalez-Lopez, T. J., Lahmer, T., Finizio, O., Ali, N., Pinczes, L. I., Lavilla-Rubira, E., Romano, A., Merelli, M., Delia, M., Calbacho, M., Meletiadis, J., Antic, D., Hernandez-Rivas, J. -A., Marques de Almeida, J., Al-Khabori, M., Hoenigl, M., Tisi, M. C., Khanna, N., Barac, A., Eisa, N., Di Blasi, R., Lievin, R., Miranda-Castillo, C., Bahr, N. C., Lamure, S., Papa, M. V., Yahya, A., Aujayeb, A., Novak, J., Erben, N., Fernandez-Galan, M., Ribera-Santa Susana, J. -M., Rinaldi, I., Fazzi, R., Piedimonte, M., Dulery, R., Gonzaga, Y., Soto-Silva, A., Sapienza, G., Serris, A., Drgona, Groh, A., Serrano, L., Gavriilaki, E., Tragiannidis, A., Prattes, J., Coppola, N., Otasevic, V., Mladenovic, M., Mitrovic, M., Miskovic, B., Jindra, P., Zompi, S., Sacchi, M. V., Krekeler, C., Infante, M. S., Garcia-Bordallo, D., Colak, G. M., Mayer, J., Nygaard, M., Hanakova, M., Racil, Z., Bonanni, Matteo, Koehler, P., Rahimli, L., Cornely, O. A., Pagano, Livio, Martin-Vallejo, F. J., Zdziarski, P., Zarrinfer, H., Wittig, J., Win, S., Wai-Man, V., Visek, B., Vinh, D. C., Vehreschild, M., Varricchio, G., Tsirigotis, P., Torres-Tienza, A., Tanase, A. D., Tafuri, A., Stamouli, M., Sramek, J., Soussain, C., Shirinova, A., Schubert, J., Schalk, E., Salehi, M. R., Saleh, M., Rosati, G., Roldan, E., Reizine, F., Rego, M., Regalado-Artamendi, I., Popova, M., Pinto, F., Philippe, L., Orth, H. M., Ommen, H. -B., Obr, A., Nunez-Martin-Buitrago, L., Noel, N., Neuhann, J., Nadali, G., Nacov, J. A., Munhoz Alburquerque, A. M., Mitra, M. E., Mikulska, M., Mellinghoff, S., Mechtel, B., Martin-Gonzalez, J. -A., Malak, S., Loureiro-Amigo, J., Lorenzo De La Pena, L., Liberti, G., Landau, M., Lacej, I., Kolditz, M., Kho, C. S., Khedr, R. A., Karthaus, M., Karlsson, L. K., Jimenez-Lorenzo, M. -J., Izuzquiza, M., Hoell-Neugebauer, B., Herbrecht, R., Heath, C. H., Guolo, F., Grothe, J., Giordano, A., Gerasymchuk, S., Garcia-Sanz, R., Garcia-Pouton, N., Funke, V. A. M., Fung, M., Flasshove, C., Fianchi, Luana, Essame, J., Egger, M., Drenou, B., Dragonetti, G., Desole, M., Della Pepa, R., Deau Fischer, B., De Kort, E., De Cabo, E., Danion, F., Daguindau, E., Cushion, T., Cremer, L., Criscuolo, Marianna, Cordini, G., Cingolani, Antonella, Ciceri, F., Chowdhury, F. R., Chelysheva, E., Chauchet, A., Chai, L. Y. A., Ceesay, M. M., Busch, E., Brehon, M., Borducchi, D. M. M., Booth, S., Bologna, S., Berg Venemyr, C., Bailen-Almorox, R., Antoniadou, A., Anastasopoulou, A. N., Altuntas, F., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Fianchi L., Criscuolo M., Cingolani A. (ORCID:0000-0002-3793-2755), Salmanton-Garcia, J., Marchesi, F., Farina, F., Weinbergerova, B., Itri, F., Davila-Valls, J., Martin-Perez, S., Glenthoj, A., Hersby, D. S., Gomes da Silva, M., Nunes Rodrigues, R., Lopez-Garcia, A., Cordoba, R., Bilgin, Y. M., Falces-Romero, I., El-Ashwah, S., Emarah, Z., Besson, C., Kohn, M., Van Doesum, J., Ammatuna, E., Marchetti, M., Labrador, J., Zambrotta, G. P. M., Verga, L., Jaksic, O., Nucci, M., Piukovics, K., Cabirta-Touzon, A., Jimenez, M., Arellano, E., Espigado, I., Blennow, O., Nordlander, A., Meers, S., van Praet, J., Aiello, T. F., Garcia-Vidal, C., Fracchiolla, N., Sciume, M., Seval, G. C., Zak, P., Buquicchio, C., Tascini, C., Grafe, S. K., Schonlein, M., Adzic-Vukicevic, T., Bonuomo, V., Cattaneo, C., Nizamuddin, S., Cernan, M., Plantefeve, G., Prin, R., Szotkovski, T., Collins, G. P., Dargenio, M., Petzer, V., Wolf, D., Colovic, N., Prezioso, L., Valkovic, T., Passamonti, F., Mendez, G. -A., Sili, U., Vena, A., Bavastro, M., Limongelli, A., Duarte, R. F., Ledoux, M. -P., Cvetanoski, M., Stojanoski, Z., Machado, M., Batinic, J., Magliano, G., Biernat, M. M., Pantic, N., Poulsen, C. B., Cuccaro, A., Del Principe, M. I., Kulasekararaj, A., Ormazabal-Velez, I., Busca, A., Demirkan, F., Ijaz, M., Klimko, N., Stoma, I., Khostelidi, S., Fernandez, N., Omrani, A. S., Bergantim, R., De Jonge, N., Fouquet, G., Navratil, M., Abu-Zeinah, G., Samarkos, M., Maertens, J., De Ramon, C., Guidetti, A., Magyari, F., Gonzalez-Lopez, T. J., Lahmer, T., Finizio, O., Ali, N., Pinczes, L. I., Lavilla-Rubira, E., Romano, A., Merelli, M., Delia, M., Calbacho, M., Meletiadis, J., Antic, D., Hernandez-Rivas, J. -A., Marques de Almeida, J., Al-Khabori, M., Hoenigl, M., Tisi, M. C., Khanna, N., Barac, A., Eisa, N., Di Blasi, R., Lievin, R., Miranda-Castillo, C., Bahr, N. C., Lamure, S., Papa, M. V., Yahya, A., Aujayeb, A., Novak, J., Erben, N., Fernandez-Galan, M., Ribera-Santa Susana, J. -M., Rinaldi, I., Fazzi, R., Piedimonte, M., Dulery, R., Gonzaga, Y., Soto-Silva, A., Sapienza, G., Serris, A., Drgona, Groh, A., Serrano, L., Gavriilaki, E., Tragiannidis, A., Prattes, J., Coppola, N., Otasevic, V., Mladenovic, M., Mitrovic, M., Miskovic, B., Jindra, P., Zompi, S., Sacchi, M. V., Krekeler, C., Infante, M. S., Garcia-Bordallo, D., Colak, G. M., Mayer, J., Nygaard, M., Hanakova, M., Racil, Z., Bonanni, Matteo, Koehler, P., Rahimli, L., Cornely, O. A., Pagano, Livio, Martin-Vallejo, F. J., Zdziarski, P., Zarrinfer, H., Wittig, J., Win, S., Wai-Man, V., Visek, B., Vinh, D. C., Vehreschild, M., Varricchio, G., Tsirigotis, P., Torres-Tienza, A., Tanase, A. D., Tafuri, A., Stamouli, M., Sramek, J., Soussain, C., Shirinova, A., Schubert, J., Schalk, E., Salehi, M. R., Saleh, M., Rosati, G., Roldan, E., Reizine, F., Rego, M., Regalado-Artamendi, I., Popova, M., Pinto, F., Philippe, L., Orth, H. M., Ommen, H. -B., Obr, A., Nunez-Martin-Buitrago, L., Noel, N., Neuhann, J., Nadali, G., Nacov, J. A., Munhoz Alburquerque, A. M., Mitra, M. E., Mikulska, M., Mellinghoff, S., Mechtel, B., Martin-Gonzalez, J. -A., Malak, S., Loureiro-Amigo, J., Lorenzo De La Pena, L., Liberti, G., Landau, M., Lacej, I., Kolditz, M., Kho, C. S., Khedr, R. A., Karthaus, M., Karlsson, L. K., Jimenez-Lorenzo, M. -J., Izuzquiza, M., Hoell-Neugebauer, B., Herbrecht, R., Heath, C. H., Guolo, F., Grothe, J., Giordano, A., Gerasymchuk, S., Garcia-Sanz, R., Garcia-Pouton, N., Funke, V. A. M., Fung, M., Flasshove, C., Fianchi, Luana, Essame, J., Egger, M., Drenou, B., Dragonetti, G., Desole, M., Della Pepa, R., Deau Fischer, B., De Kort, E., De Cabo, E., Danion, F., Daguindau, E., Cushion, T., Cremer, L., Criscuolo, Marianna, Cordini, G., Cingolani, Antonella, Ciceri, F., Chowdhury, F. R., Chelysheva, E., Chauchet, A., Chai, L. Y. A., Ceesay, M. M., Busch, E., Brehon, M., Borducchi, D. M. M., Booth, S., Bologna, S., Berg Venemyr, C., Bailen-Almorox, R., Antoniadou, A., Anastasopoulou, A. N., Altuntas, F., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Fianchi L., Criscuolo M., and Cingolani A. (ORCID:0000-0002-3793-2755)
Abstract: Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe
Published: 2024

4. Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry

Author: Musto, P., Salmanton-Garcia, J., Sgherza, N., Bergantim, R., Farina, F., Glenthoj, A., Cengiz Seval, G., Weinbergerova, B., Bonuomo, V., Bilgin, Y. M., van Doesum, J., Jaksic, O., Visek, B., Falces-Romero, I., Marchetti, M., Davila-Valls, J., Martin-Perez, S., Nucci, M., Lopez-Garcia, A., Itri, F., Buquicchio, C., Verga, L., Piukovics, K., Navratil, M., Collins, G. P., Jimenez, M., Fracchiolla, N. S., Labrador, J., Prezioso, L., Rossi, E., Colovic, N., Meers, S., Kulasekararaj, A., Cuccaro, A., Blennow, O., Valkovic, T., Sili, U., Ledoux, M. -P., Batinic, J., Passamonti, F., Machado, M., Duarte, R. F., Poulsen, C. B., Mendez, G. -A., Espigado, I., Demirkan, F., Cernan, M., Cattaneo, C., Petzer, V., Magliano, G., Garcia-Vidal, C., El-Ashwah, S., Gomes-Da-Silva, M., Vena, A., Ormazabal-Velez, I., van Praet, J., Dargenio, M., De-Ramon, C., Del Principe, M. I., Marques-De-Almeida, J., Wolf, D., Szotkowski, T., Obr, A., Colak, G. M., Nordlander, A., Izuzquiza, M., Cabirta, A., Zambrotta, G. P. M., Cordoba, R., Zak, P., Ammatuna, E., Mayer, J., Ilhan, O., Garcia-Sanz, R., Quattrone, Martina, Arellano, E., Nunes-Rodrigues, R., Emarah, Z., Aiello, T. F., Hanakova, M., Racil, Z., Bavastro, M., Limongelli, A., Rahimli, L., Marchesi, F., Cornely, O. A., Pagano, Livio, Quattrone M., Pagano L. (ORCID:0000-0001-8287-928X), Musto, P., Salmanton-Garcia, J., Sgherza, N., Bergantim, R., Farina, F., Glenthoj, A., Cengiz Seval, G., Weinbergerova, B., Bonuomo, V., Bilgin, Y. M., van Doesum, J., Jaksic, O., Visek, B., Falces-Romero, I., Marchetti, M., Davila-Valls, J., Martin-Perez, S., Nucci, M., Lopez-Garcia, A., Itri, F., Buquicchio, C., Verga, L., Piukovics, K., Navratil, M., Collins, G. P., Jimenez, M., Fracchiolla, N. S., Labrador, J., Prezioso, L., Rossi, E., Colovic, N., Meers, S., Kulasekararaj, A., Cuccaro, A., Blennow, O., Valkovic, T., Sili, U., Ledoux, M. -P., Batinic, J., Passamonti, F., Machado, M., Duarte, R. F., Poulsen, C. B., Mendez, G. -A., Espigado, I., Demirkan, F., Cernan, M., Cattaneo, C., Petzer, V., Magliano, G., Garcia-Vidal, C., El-Ashwah, S., Gomes-Da-Silva, M., Vena, A., Ormazabal-Velez, I., van Praet, J., Dargenio, M., De-Ramon, C., Del Principe, M. I., Marques-De-Almeida, J., Wolf, D., Szotkowski, T., Obr, A., Colak, G. M., Nordlander, A., Izuzquiza, M., Cabirta, A., Zambrotta, G. P. M., Cordoba, R., Zak, P., Ammatuna, E., Mayer, J., Ilhan, O., Garcia-Sanz, R., Quattrone, Martina, Arellano, E., Nunes-Rodrigues, R., Emarah, Z., Aiello, T. F., Hanakova, M., Racil, Z., Bavastro, M., Limongelli, A., Rahimli, L., Marchesi, F., Cornely, O. A., Pagano, Livio, Quattrone M., and Pagano L. (ORCID:0000-0001-8287-928X)
Abstract: Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109/L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.
Published: 2024

5. Report of Consensus Panel 4 from the 11th International Workshop on Waldenstrom's Macroglobulinemia on Diagnostic and Response Criteria

Author: Treon, SP, primary, Tedeschi, A, additional, San-Miguel, J, additional, Garcia-Sanz, R, additional, Anderson, KC, additional, Kimby, E, additional, Minnema, MC, additional, Benevolo, G, additional, Qiu, L, additional, Yi, S, additional, Terpos, E, additional, Tam, CS, additional, Castillo, JJ, additional, Morel, P, additional, Dimopoulos, M, additional, and Owen, RG, additional
Published: 2023
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6. Report of Consensus Panel 3 from the 11th International Workshop on Waldenström's Macroglobulinemia: Recommendations for Molecular Diagnosis in Waldenström's Macroglobulinemia

Author: Garcia-Sanz, R, primary, Varettoni, M, additional, Jiménez, C, additional, Ferrero, S, additional, Poulain, S, additional, San-Miguel, JF, additional, Guerrera, ML, additional, Drandi, D, additional, Bagratuni, T, additional, McMaster, M, additional, Roccaro, AM, additional, Roos-Weil, D, additional, Leiba, M, additional, Li, Y, additional, Qiu, L, additional, Hou, J, additional, De Larrea, C Fernandez, additional, Castillo, JJ, additional, Dimopoulos, M, additional, Owen, RG, additional, Treon, SP, additional, and Hunter, ZR, additional
Published: 2023
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7. Impact of SARS-CoV-2 vaccination and monoclonal antibodies on outcome post–CD19-directed CAR T-cell therapy: an EPICOVIDEHA survey

Author: van Doesum, J. A., Salmanton-Garcia, J., Marchesi, F., Blasi, R. D., Falces-Romero, I., Cabirta, A., Farina, F., Besson, C., Weinbergerova, B., Van Praet, J., Schonlein, M., Lopez-Garcia, A., Lamure, S., Guidetti, A., De Ramon-Sanchez, C., Batinic, J., Gavriilaki, E., Tragiannidis, A., Tisi, M. C., Plantefeve, G., Petzer, V., Ormazabal-Velez, I., Almeida, J. M. D., Marchetti, M., Maertens, J., Machado, M., Kulasekararaj, A., Hernandez-Rivas, J. -A., Silva, M. G. D., Fernandez, N., Espigado, I., Drgona, L., Dragonetti, Giulia, Metafuni, Elisabetta, Calbacho, M., Blennow, O., Wolf, D., van Anrooij, B., Rodrigues, R. N., Nordlander, A., Martin-Gonzalez, J. -A., Lievin, R., Jimenez, M., Grafe, S. K., Garcia-Sanz, R., Cordoba, R., Rahimli, L., van Meerten, T., Cornely, O. A., Pagano, Livio, Dragonetti G., Metafuni E., Pagano L. (ORCID:0000-0001-8287-928X), van Doesum, J. A., Salmanton-Garcia, J., Marchesi, F., Blasi, R. D., Falces-Romero, I., Cabirta, A., Farina, F., Besson, C., Weinbergerova, B., Van Praet, J., Schonlein, M., Lopez-Garcia, A., Lamure, S., Guidetti, A., De Ramon-Sanchez, C., Batinic, J., Gavriilaki, E., Tragiannidis, A., Tisi, M. C., Plantefeve, G., Petzer, V., Ormazabal-Velez, I., Almeida, J. M. D., Marchetti, M., Maertens, J., Machado, M., Kulasekararaj, A., Hernandez-Rivas, J. -A., Silva, M. G. D., Fernandez, N., Espigado, I., Drgona, L., Dragonetti, Giulia, Metafuni, Elisabetta, Calbacho, M., Blennow, O., Wolf, D., van Anrooij, B., Rodrigues, R. N., Nordlander, A., Martin-Gonzalez, J. -A., Lievin, R., Jimenez, M., Grafe, S. K., Garcia-Sanz, R., Cordoba, R., Rahimli, L., van Meerten, T., Cornely, O. A., Pagano, Livio, Dragonetti G., Metafuni E., and Pagano L. (ORCID:0000-0001-8287-928X)
Abstract: Patients with previous CD19-directed chimeric antigen receptor (CAR) T-cell therapy have a prolonged vulnerability to viral infections. Coronavirus disease 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real-world data on the impact of vaccination and treatment on patients with COVID-19 after CD19-directed CAR T-cell therapy are lacking. Therefore, this multicenter, retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared with patients infected with previous variants (7% vs 58% [P = .012]). Twenty-six patients were vaccinated at the time of the COVID-19 diagnosis. Two vaccinations showed a marked but unsignificant reduction in the risk of COVID-19–caused mortality (33.3% vs 14.2% [P = .379]). In addition, the course of the disease appears milder with less frequent intensive care unit admissions (39% vs 14% [P = .054]) and a shorter duration of hospitalization (7 vs 27.5 days [P = .022]). Of the available treatment options, only monoclonal antibodies seemed to be effective at reducing mortality from 32% to 0% (P = .036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death. This trial was registered at www.clinicaltrials.gov as #NCT04733729.
Published: 2023

8. Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings

Author: Rossi, G., Salmanton-Garcia, J., Cattaneo, C., Marchesi, F., Davila-Valls, J., Martin-Perez, S., Itri, F., Lopez-Garcia, A., Glenthoj, A., Da Silva, M. G., Besson, C., Marchetti, M., Weinbergerova, B., Jaksic, O., Jimenez, M., Bilgin, Y. M., Van Doesum, J., Farina, F., Ak, P., Verga, L., Collins, G. P., Bonuomo, V., Praet, J. V., Nucci, M., Meers, S., Espigado, I., Fracchiolla, N. S., Valkovic, T., Poulsen, C. B., Colovic, N., Dragonetti, Giulia, Ledoux, M. -P., Tascini, C., Buquicchio, C., Blennow, O., Passamonti, F., Machado, M., Labrador, J., Duarte, R. F., Schonlein, M., Prezioso, L., Falces-Romero, I., Kulasekararaj, A., Garcia-Vidal, C., Fernandez, N., Abu-Zeinah, G., Ormazabal-Velez, I., Ad ic-Vukicevic, T., Piukovics, K., Stoma, I., Cuccaro, A., Magliano, G., Szotkowski, T., Gonzalez-Lopez, T. -J., El-Ashwah, S., Bergantim, R., Sili, U., Maertens, J., Demirkan, F., De Ramon, C., Petzer, V., Del Principe, M. I., Navratil, M., Dargenio, M., Seval, G. C., Samarkos, M., Racil, Z., Pinczes, L. I., Lahmer, T., Busca, A., Mendez, G. -A., Vena, A., Biernat, M. M., Merelli, M., Calbacho, M., Barac, A., Bavastro, M., Limongelli, A., Ilhan, O., Wolf, D., Colak, G. M., Garcia-Sanz, R., Emarah, Z., Mi kovic, B., Grafe, S. K., Mladenovic, M., Aiello, T. F., Nunez-Martin-Buitrago, L., Nordlander, A., Arellano, E., Zambrotta, G. P. M., Ammatuna, E., Cabirta, A., Sacchi, M. V., Rodrigues, R. N., Hersby, D. S., Hanakova, M., Rahimli, L., Cordoba, R., Cornely, O. A., Pagano, Livio, Marques De, Almeida, Hernandez-Rivas, Marques De Almeida, J., Hernandez-Rivas, J. A., Guidetti, A., Finizio, O., Stojanoski, Z., Cvetanoski, M., Meletiadis, J., De Jonge, N., Antic, D., Ali, N., Tisi, M. C., Serrano, L., Plantefeve, G., Khanna, N., Hoenigl, M., Cernan, M., Miranda-Castillo, C., Fernandez-Galan, M., Serris, A., Erben, N., Dulery, R., Aujayeb, A., Papa, M. V., Novak, J., Delia, M., Sapienza, G., Reizine, F., Omrani, A. S., Di Blasi, R., Lamure, S., Drgona, L., Coppola, N., Batinic, J., Al-Khabori, M., Ribera-Santa Susana, J. -M., Piedimonte, M., Loureiro-Amigo, J., Fouquet, G., Fazzi, R., Danion, F., Schubert, J., Hoell-Neugebauer, B., Bahr, N. C., Yahia, A. O., Torres-Atienza, A., Rinaldi, I., Popova, M., Ommen, H. -B., Mitra, M. E., Mikulska, M., Lacej, I., Khostelidi, S., Win, S., Vinh, D., Saleh, M., Prattes, J., Jindra, P., Guolo, F., Della Pepa, R., Chelysheva, E., Zdziarski, P., Wai-Man, V., Soto-Silva, A., Orth, H. M., Malak, S., Lorenzo De La Pena, L., Kolditz, M., Kho, C. S., Heath, C. H., Groh, A., Gavriilaki, E., Fung, M., Egger, M., De Kort, E., De Cabo, E., Cushion, T., Chowdhury, F. R., Ceesay, M. M., Brehon, M., Varricchio, G., Tafuri, A., Jimenez-Lorenzo, M. -J., Klimko, N., Tsirigotis, P., Antoniadou, A., Vehreschild, M., Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Rossi, G., Salmanton-Garcia, J., Cattaneo, C., Marchesi, F., Davila-Valls, J., Martin-Perez, S., Itri, F., Lopez-Garcia, A., Glenthoj, A., Da Silva, M. G., Besson, C., Marchetti, M., Weinbergerova, B., Jaksic, O., Jimenez, M., Bilgin, Y. M., Van Doesum, J., Farina, F., Ak, P., Verga, L., Collins, G. P., Bonuomo, V., Praet, J. V., Nucci, M., Meers, S., Espigado, I., Fracchiolla, N. S., Valkovic, T., Poulsen, C. B., Colovic, N., Dragonetti, Giulia, Ledoux, M. -P., Tascini, C., Buquicchio, C., Blennow, O., Passamonti, F., Machado, M., Labrador, J., Duarte, R. F., Schonlein, M., Prezioso, L., Falces-Romero, I., Kulasekararaj, A., Garcia-Vidal, C., Fernandez, N., Abu-Zeinah, G., Ormazabal-Velez, I., Ad ic-Vukicevic, T., Piukovics, K., Stoma, I., Cuccaro, A., Magliano, G., Szotkowski, T., Gonzalez-Lopez, T. -J., El-Ashwah, S., Bergantim, R., Sili, U., Maertens, J., Demirkan, F., De Ramon, C., Petzer, V., Del Principe, M. I., Navratil, M., Dargenio, M., Seval, G. C., Samarkos, M., Racil, Z., Pinczes, L. I., Lahmer, T., Busca, A., Mendez, G. -A., Vena, A., Biernat, M. M., Merelli, M., Calbacho, M., Barac, A., Bavastro, M., Limongelli, A., Ilhan, O., Wolf, D., Colak, G. M., Garcia-Sanz, R., Emarah, Z., Mi kovic, B., Grafe, S. K., Mladenovic, M., Aiello, T. F., Nunez-Martin-Buitrago, L., Nordlander, A., Arellano, E., Zambrotta, G. P. M., Ammatuna, E., Cabirta, A., Sacchi, M. V., Rodrigues, R. N., Hersby, D. S., Hanakova, M., Rahimli, L., Cordoba, R., Cornely, O. A., Pagano, Livio, Marques De, Almeida, Hernandez-Rivas, Marques De Almeida, J., Hernandez-Rivas, J. A., Guidetti, A., Finizio, O., Stojanoski, Z., Cvetanoski, M., Meletiadis, J., De Jonge, N., Antic, D., Ali, N., Tisi, M. C., Serrano, L., Plantefeve, G., Khanna, N., Hoenigl, M., Cernan, M., Miranda-Castillo, C., Fernandez-Galan, M., Serris, A., Erben, N., Dulery, R., Aujayeb, A., Papa, M. V., Novak, J., Delia, M., Sapienza, G., Reizine, F., Omrani, A. S., Di Blasi, R., Lamure, S., Drgona, L., Coppola, N., Batinic, J., Al-Khabori, M., Ribera-Santa Susana, J. -M., Piedimonte, M., Loureiro-Amigo, J., Fouquet, G., Fazzi, R., Danion, F., Schubert, J., Hoell-Neugebauer, B., Bahr, N. C., Yahia, A. O., Torres-Atienza, A., Rinaldi, I., Popova, M., Ommen, H. -B., Mitra, M. E., Mikulska, M., Lacej, I., Khostelidi, S., Win, S., Vinh, D., Saleh, M., Prattes, J., Jindra, P., Guolo, F., Della Pepa, R., Chelysheva, E., Zdziarski, P., Wai-Man, V., Soto-Silva, A., Orth, H. M., Malak, S., Lorenzo De La Pena, L., Kolditz, M., Kho, C. S., Heath, C. H., Groh, A., Gavriilaki, E., Fung, M., Egger, M., De Kort, E., De Cabo, E., Cushion, T., Chowdhury, F. R., Ceesay, M. M., Brehon, M., Varricchio, G., Tafuri, A., Jimenez-Lorenzo, M. -J., Klimko, N., Tsirigotis, P., Antoniadou, A., Vehreschild, M., Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)
Abstract: Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.
Published: 2023

9. Report of consensus panel 7 from the 11th international workshop on Waldenström macroglobulinemia on priorities for novel clinical trials

Author: Tam, CS, primary, Kapoor, P, additional, Castillo, JJ, additional, Buske, C, additional, Ansell, SM, additional, Branagan, AR, additional, Kimby, E, additional, Li, Y, additional, Palomba, ML, additional, Qiu, L, additional, Shadman, M, additional, Abeykoon, JP, additional, Sarosiek, S, additional, Vos, JMI, additional, Yi, S, additional, Stephens, D, additional, Roos-Weil, D, additional, Roccaro, AM, additional, Morel, P, additional, Munshi, NC, additional, Anderson, KC, additional, San-Miguel, J, additional, Garcia-Sanz, R, additional, Dimopoulos, MA, additional, Treon, SP, additional, and Kersten, MJ, additional
Published: 2023
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10. Report of consensus panel 2 from the 11th international workshop on Waldenström's macroglobulinemia on the management of relapsed or refractory WM patients

Author: D'Sa, S, primary, Matous, JV, additional, Advani, R, additional, Buske, C, additional, Castillo, JJ, additional, Gatt, M, additional, Kapoor, P, additional, Kersten, MJ, additional, Leblond, V, additional, Leiba, M, additional, Palomba, ML, additional, Paludo, J, additional, Qiu, L, additional, Sarosiek, S, additional, Shadman, M, additional, Talaulikar, D, additional, Tam, CS, additional, Tedeschi, A, additional, Thomas, SK, additional, Tohidi-Esfahani, I, additional, Trotman, J, additional, Varettoni, M, additional, Vos, JMI, additional, Garcia-Sanz, R, additional, San-Miguel, J, additional, Dimopoulos, MA, additional, Treon, SP, additional, and Kastritis, E, additional
Published: 2023
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11. SARS-CoV-2 Infection in Patients with Waldenstrom's Macroglobulinemia: A Multicenter International Cohort Study

Author: Defrancesco, I., Ferretti, V. V., Morel, P., Kyriakou, C., Kastritis, E., Tohidi-Esfahani, I., Tedeschi, A., Buske, C., Garcia-Sanz, R., Vos, J. M. I., Peri, V., Margiotta Casaluci, G., Ferrari, A., Piazza, F., Oostvogels, R., Lovato, E., Montes, L., Fornecker, L. M., Grunenberg, A., Dimopoulos, M. A., Tam, C. S., D'Sa, S., Leblond, V., Trotman, J., Passamonti, F., Arcaini, L., and Varettoni, M.
Published: 2023

12. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey

Author: Pagano, Livio, Salmanton-Garcia, J., Marchesi, F., Blennow, O., Gomes da Silva, M., Glenthoj, A., van Doesum, J., Bilgin, Y. M., Lopez-Garcia, A., Itri, F., Nunes Rodrigues, R., Weinbergerova, B., Farina, F., Dragonetti, Giulia, Berg Venemyr, C., van Praet, J., Jaksic, O., Valkovic, T., Falces-Romero, I., Martin-Perez, S., Jimenez, M., Davila-Valls, J., Schonlein, M., Ammatuna, E., Meers, S., Delia, M., Stojanoski, Z., Nordlander, A., Lahmer, T., Imre Pinczes, L., Buquicchio, C., Piukovics, K., Ormazabal-Velez, I., Fracchiolla, N., Samarkos, M., Mendez, G. -A., Hernandez-Rivas, J. -A., Espigado, I., Cernan, M., Petzer, V., Lamure, S., di Blasi, R., Marques de Almedia, J., Dargenio, M., Biernat, M. M., Sciume, M., de Ramon, C., de Jonge, N., Batinic, J., Aujayeb, A., Marchetti, M., Fouquet, G., Fernandez, N., Zambrotta, G., Sacchi, M. V., Guidetti, A., Demirkan, F., Prezioso, L., Racil, Z., Nucci, M., Mladenovic, M., Lievin, R., Hanakova, M., Grafe, S., Sili, U., Machado, M., Cattaneo, C., Adzic-Vukicevic, T., Verga, L., Labrador, J., Rahimli, L., Bonanni, Matteo, Passamonti, F., Pagliuca, A., Corradini, P., Hoenigl, M., Koehler, P., Busca, A., Cornely, O. A., Serrano, L., Ribera-Santa Susana, J. -M., Meletiadis, J., Tsirigotis, P., Coppola, N., Mikulska, M., Erben, N., Besson, C., Merelli, M., Gonzalez-Lopez, T. -J., Loureiro-Amigo, J., Garcia-Vidal, C., Kort, E. D., Cuccaro, A., Zompi, S., Reizine, F., Finizio, O., Dulery, R., Calbacho, M., Abu-Zeinah, G., Malak, S., Zdziarski, P., Varrichio, G., Tragiannidis, A., Plantefeve, G., Duarte, R., Danion, F., Tisi, M. C., Sakellari, I., Karthaus, M., Groh, A., Fung, M., Emarah, Z., Coronel-Ayala, O. -F., Ann Chai, L. Y., Brehon, M., Bonuomo, V., Wolf, D., Wittig, J., Vehreschild, M., Papa, M. V., Neuhann, J., Jimenez-Lorenzo, M. -J., Grothe, J., Gavriilaki, E., Garcia-Sanz, R., Garcia-Pouton, N., El-Ashwah, S. S., Eggerer, M., Cordoba, R., Colak, G. M., Arellano, E., Hematology, Pagano L., Salmanton-García J., Marchesi F., Blennow O., Gomes da Silva M., Glenthøj A., van Doesum J., Bilgin Y. M. , López-García A., Itri F., et al., and Gilead Sciences
Subjects: Internal Diseases, Clinical Trials and Observations, CELL BIOLOGY, Cardiorespiratory Medicine and Haematology, Sağlık Bilimleri, Fundamental Medical Sciences, Biochemistry, İç Hastalıkları, Clinical Medicine (MED), COVID-19 Testing, BİYOKİMYA VE MOLEKÜLER BİYOLOJİ, Biyokimya, Monoclonal, Klinik Tıp (MED), 03.02. Klinikai orvostan, Viral, Lung, Cancer, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, Lymphoid Neoplasia, Myeloid Neoplasia, Klinik Tıp, Hücre Biyolojisi, Temel Bilimler, HEMATOLOJİ, Life Sciences, HÜCRE BİYOLOJİSİ, Tıp, MOLECULAR BIOLOGY & GENETICS, Infectious Diseases, Hematologic Neoplasms, Medicine, Natural Sciences, Infection, BIOCHEMISTRY & MOLECULAR BIOLOGY, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Sitogenetik, Biotechnology, Adult, Clinical Sciences, Immunology, Temel Tıp Bilimleri, Histoloji-Embriyoloji, Life Sciences (LIFE), Molecular Biology and Genetics, Antiviral Agents, Antibodies, Vaccine Related, Paediatrics and Reproductive Medicine, HEMATOLOGY, Biodefense, Yaşam Bilimleri, Health Sciences, Humans, CVOID19, Cytogenetic, Free Research Articles, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, Moleküler Biyoloji ve Genetik, Internal Medicine Sciences, İmmünoloji, SARS-CoV-2, Histology and Embryology, Prevention, COVID-19, Dahili Tıp Bilimleri, CLINICAL MEDICINE, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15 - MALATTIE DEL SANGUE, Emerging Infectious Diseases, Good Health and Well Being, Yaşam Bilimleri (LIFE), Hematoloji, Immunization
Abstract: Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals., EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).
Published: 2022
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13. ASPEN: Results of a phase 3 randomized trial of zanubrutinib versus ibrutinib for patients with Waldenstrom Macroglobulinemia (WM).

Author: Buske C., Dimopoulos M., Opat S., D'Sa S., Jurczak W., Lee H.-P., Cull G., Owen R.G., Marlton P., Wahlin B.E., Garcia Sanz R., McCarthy H., Mulligan S., Tedeschi A., Castillo J., Czyz J., Fernandez De Larrea C., Belada D., Libby E., Matous J., Motta M., Siddiqi T., Tani M., Trneny M., Minnema M., Leblond V., Chan W.Y., Schneider J., Cohen A., Huang J., Tam C.S., Buske C., Dimopoulos M., Opat S., D'Sa S., Jurczak W., Lee H.-P., Cull G., Owen R.G., Marlton P., Wahlin B.E., Garcia Sanz R., McCarthy H., Mulligan S., Tedeschi A., Castillo J., Czyz J., Fernandez De Larrea C., Belada D., Libby E., Matous J., Motta M., Siddiqi T., Tani M., Trneny M., Minnema M., Leblond V., Chan W.Y., Schneider J., Cohen A., Huang J., and Tam C.S.
Abstract: Introduction: Bruton's tyrosine kinase (BTK) inhibition is an emerging standard of care for WM. The ASPEN trial (NCT03053440) is a randomized phase 3 study comparing zanubrutinib, a potent and selective BTK inhibitor, versus ibrutinib, a first generation BTK inhibitor, in patients with WM. Method(s): Patients with MYD88 mutation-positive (MYD88mut+) WM were randomly assigned 1:1 to receive zanubrutinib (160 mg twice daily) or ibrutinib (420 mg once daily). Patients without MYD88 mutations were assigned to a separate cohort, received zanubrutinib, and are reported separately. Randomization was stratified by CXCR4 mutational status and the number of lines of prior therapy (0 vs 1-3 vs >3). The primary end point was the proportion of patients achieving a complete response or very good partial response (CR+VGPR). Sample size was calculated to provide 81% power to detect a difference in CR+VGPR rate of 35% vs 15% in the subset of patients with relapsed or refractory WM. Primary analysis was planned to occur at ~12 months after the last patient enrolled. Result(s): In total, 201 patients were randomized from Jan 2017 to Jul 2018. The treatment groups were well balanced for important baseline factors, with the exception of more elderly patients (aged >75 years, 33.3% vs 22.2%) and more anemia (hemoglobin <=110 g/L, 65.7% vs 53.5%) in the zanubrutinib arm. At a median follow-up of 19.4 months, the rate of VGPR (no CRs were observed) was 28.4% vs 19.2% with zanubrutinib vs ibrutinib, respectively (2-sided P=0.09). Rates of atrial fibrillation, contusion, diarrhea, edema peripheral, hemorrhage, muscle spasms, pneumonia, and adverse events leading to discontinuation or death were lower with zanubrutinib. The rate of neutropenia was higher with zanubrutinib (Table), but grade >=3 infection rates were similar (17.8% vs 19.4%). Conclusion(s): ASPEN is the largest phase 3 trial of BTK inhibitors in WM and the first head-to-head comparison of BTK inhibitors in any disease. Although
Published: 2022

14. Updated results of the aspen trial from a cohort of patients with wild-type myd88 waldenstrom macroglobulinemia (myd88wt wm).

Author: Buske C., Dimopoulos M., Garcia Sanz R., Lee H.-P., Trneny M., Varettoni M., Opat S., D'Sa S., Owen R.G., Cull G., Mulligan S., Czyz J., Castillo J., Motta M., Siddiqi T., Gironella Mesa M., Granell Gorrochategui M., Talaulikar D., Zinzani P.L., Askari E., Grosicki S., Oriol A., Kloczko J., Tedeschi A., Leblond V., Chan W.Y., Schneider J., Cohen A., Huang J., Tam C.S., Buske C., Dimopoulos M., Garcia Sanz R., Lee H.-P., Trneny M., Varettoni M., Opat S., D'Sa S., Owen R.G., Cull G., Mulligan S., Czyz J., Castillo J., Motta M., Siddiqi T., Gironella Mesa M., Granell Gorrochategui M., Talaulikar D., Zinzani P.L., Askari E., Grosicki S., Oriol A., Kloczko J., Tedeschi A., Leblond V., Chan W.Y., Schneider J., Cohen A., Huang J., and Tam C.S.
Abstract: Introduction: Inhibitors of Bruton's tyrosine kinase (BTK) have shown significant activity in patients with MYD88 mutation-positive (MYD-88mut+) WM. However, lower response rates and shorter progression-free survival have been reported in patients with WM who lack such mutations (N Engl J Med. 2015;372:1430). The ASPEN trial (NCT03053440) evaluated zanubrutinib, a potent and selective BTK inhibitor, in patients with MYD88WT WM. Here, we present the safety and efficacy of zanubrutinib in these patients. Method(s): At study entry, bone marrow MYD88 mutations were assessed by a central laboratory (NeoGenomics). Based on these results, patients were assigned to cohort 1 (MYD88mut+) or cohort 2 (MYD88WT or unknown mutation status). Patients received zanubrutinib 160 mg twice daily until disease progression. Result(s): In total, 28 patients were enrolled in cohort 2, of which 26 were centrally confirmed as MYD88WT. Median age of patients was 72 years; five patients were treatment-naive and 23 patients had relapsed/refractory (>=1 prior therapy) WM. Most patients had intermediate-risk (39.3%) or high-risk (42.9%) disease, as defined by the International Prognostic Scoring System for WM. At median follow-up of 17.9 months, two patients discontinued zanubrutinib due to adverse events (AEs), and six experienced disease progression; there were no cases of disease transformation. In patients with confirmed MYD88WT, the overall response rate by independent review was 80.8%, with a major response rate of 50.0%, including a very good partial response rate of 26.9%. The progression-free survival event-free rate at 12 months was 72.4%. The most frequently reported AEs were diarrhea, anemia, contusion, pyrexia, and upper respiratory tract infection. Major hemorrhage was reported in two patients, and atrial fibrillation was reported in one patient. There were no fatal AEs. Conclusion(s): Zanubrutinib showed clinically meaningful antitumor activity, including achieving major responses
Published: 2022

15. A strategic reflection for the management and implementation of CAR-T therapy in Spain : an expert consensus paper

Author: Zozaya, Néboa, Villaseca Carmena, Javier, Abdalla, Fernando, Calleja Hernández, Miguel Ángel, Díez-Martín, José Luis, Estévez, J., Garcia-Sanz, R., Martínez-López, Joaquín, Sierra, Jorge, Vera, Ruth, Hidalgo, Álvaro, Universitat Autònoma de Barcelona, Zozaya, Néboa, Villaseca Carmena, Javier, Abdalla, Fernando, Calleja Hernández, Miguel Ángel, Díez-Martín, José Luis, Estévez, J., Garcia-Sanz, R., Martínez-López, Joaquín, Sierra, Jorge, Vera, Ruth, Hidalgo, Álvaro, and Universitat Autònoma de Barcelona
Abstract: CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.
Published: 2022

16. ASPEN: Long-term follow-up results of a phase 3 randomized trial of zanubrutinib (ZANU) versus ibrutinib (IBR) in patients with Waldenstrom macroglobulinemia (WM).

Author: Tam C.S.L., Garcia-Sanz R., Opat S., D'Sa S., Jurczak W., Lee H.-P., Cull G., Owen R.G., Marlton P., Wahlin B.E., Tedeschi A., Castillo J.J., Siddiqi T., Buske C., Leblond V., Chan W.Y., Schneider J., Cohen A., Huang J., Dimopoulos M.A., Tam C.S.L., Garcia-Sanz R., Opat S., D'Sa S., Jurczak W., Lee H.-P., Cull G., Owen R.G., Marlton P., Wahlin B.E., Tedeschi A., Castillo J.J., Siddiqi T., Buske C., Leblond V., Chan W.Y., Schneider J., Cohen A., Huang J., and Dimopoulos M.A.
Abstract: Background: ASPEN is a randomized, open-label, phase 3 study comparing ZANU, a potent and selective Bruton tyrosine kinase inhibitor (BTKi), with the first-generation BTKi IBR in patients with WM. We present data with a median follow-up of 43 months. Method(s): Patients with MYD88 mutations were assigned to cohort 1 and randomized 1:1 to receive ZANU 160 mg twice daily or IBR 420 mg once daily. Randomization was stratified by CXCR4 mutational status and lines of prior therapy (0 vs 1-3 vs > 3). Patients without MYD88 mutations were assigned to cohort 2 and received ZANU 160 mg twice daily. The primary endpoint was proportion of patients achieving complete response or very good partial response (CR+VGPR). Result(s): A total of 201 patients (ZANU arm, n = 102; IBR arm, n = 99) were enrolled in cohort 1 and 28 patients were enrolled in cohort 2. A larger proportion of patients in the ZANU arm of cohort 1 vs IBR had CXCR4 mutations by next-generation sequencing (32% vs 20%, or 33 of 98 vs 20 of 92 with data available) and were aged > 75 years (33% vs 22%). Median duration of treatment was 42 months (ZANU) and 41 months (IBR), with 67% and 58% remaining on treatment, respectively. The CR+VGPR rate by investigator was 36% with ZANU vs 22% with IBR (p= 0.02) in cohort 1, and 31% in cohort 2. One patient achieved CR (cohort 2). In patients with wild type or mutant CXCR4 from cohort 1, CR+VGPR rates with ZANU vs IBR were 45% vs 28% (p= 0.04) and 21% vs 5% (p= 0.15), respectively. Median progression-free survival and overall survival were not yet reached. Rates of atrial fibrillation, diarrhea, hypertension, localized infection, hemorrhage, muscle spasms, pneumonia, and adverse events leading to discontinuation or death were lower with ZANU vs IBR (Table). Exposure-adjusted incidence rates of atrial fibrillation/flutter and hypertension were lower with ZANU vs IBR (0.2 vs 0.8 and 0.5 vs 1.0 persons per 100 person-months, respectively; p< 0.05). Rate of neutropenia was higher
Published: 2022

17. Aspen: long-term follow-up results of a phase 3 randomized trial of zanubrutinib (zanu) vs ibrutinib (ibr) in patients (pts) with waldenstrom macroglobulinemia (wm).

Author: Dimopoulos M., Opat S., D'Sa S., Jurczak W., Lee H.-P., Cull G., Owen R.G., Marlton P., Wahlin B.E., Garcia-Sanz R., McCarthy H., Mulligan S., Tedeschi A., Castillo J.J., Czyz J., De Larrea Rodriguez C.F., Belada D., Libby E., Matous J., Motta M., Siddiqi T., Tani M., Trneny M., Minnema M., Buske C., Leblond V., Treon S.P., Trotman J., Chan W.Y., Schneider J., Allewelt H., Cohen A., Huang J., Tam C.S., Dimopoulos M., Opat S., D'Sa S., Jurczak W., Lee H.-P., Cull G., Owen R.G., Marlton P., Wahlin B.E., Garcia-Sanz R., McCarthy H., Mulligan S., Tedeschi A., Castillo J.J., Czyz J., De Larrea Rodriguez C.F., Belada D., Libby E., Matous J., Motta M., Siddiqi T., Tani M., Trneny M., Minnema M., Buske C., Leblond V., Treon S.P., Trotman J., Chan W.Y., Schneider J., Allewelt H., Cohen A., Huang J., and Tam C.S.
Abstract: Background: ZANU is a potent and selective next-generation Bruton tyrosine kinase inhibitor (BTKi) designed to have greater affinity to BTK while minimizing off-target inhibition of TEC-and EGFR-family kinases. ASPEN (NCT03053440) is a randomized, open-label, phase 3 study comparing ZANU with the first-generation BTKi IBR in pts with WM. We present data with a median follow-up of 43 months. Aim(s): To compare the efficacy and safety of ZANU vs IBR in pts with MYD88 mutant (MYD88mut) WM and ZANU in pts with wild-type MYD88 (MYD88wt) WM. Method(s): Pts with MYD88mut WM were assigned to cohort 1 and randomized 1:1 to receive ZANU 160 mg twice daily or IBR 420 mg once daily. Pts with MYD88wt were assigned to cohort 2 and received ZANU 160 mg twice daily until disease progression. Randomization was stratified by CXCR4 mutational status by Sanger sequencing and lines of prior therapy (0, 1-3, or >3). All pts gave informed consent. The primary endpoint was proportion of pts achieving very good partial response or better (VGPR + complete response [CR]). Primary analysis occurred at 19 months median follow-up, and final analysis is planned to occur ~4 years after the first pt enrolled. Result(s): A total of 201 pts (102 ZANU; 99 IBR) were enrolled in cohort 1 and 28 pts in cohort 2. Baseline characteristics in cohort 1 differed between pts treated with ZANU vs IBR in CXCR4 mutations by next-generation sequencing (32% vs 20%, or 33 of 98 vs 20 of 92 available samples, respectively) and pts aged >75 years (33% vs 22%, respectively). Median duration of treatment was 42 months (ZANU) and 41 months (IBR), with 67% and 58% remaining on treatment, respectively. The VGPR+CR rate by investigator was 36% with ZANU vs 22% with IBR (descriptive p = 0.02) in cohort 1, and 31% in cohort 2. One pt in cohort 2 obtained a CR. In pts with wild-type (65 ZANU; 72 IBR) or mutant CXCR4 (33 ZANU; 20 IBR) from cohort 1, VGPR+CR rates with ZANU vs IBR were 45% vs 28% (p = 0.04) and 21% vs 5% (p = 0.
Published: 2022

18. Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenstrom's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study

Author: Buske, C, Tedeschi, A, Trotman, J, Garcia-Sanz, R, MacDonald, D, Leblond, V, Mahe, B, Herbaux, C, Matous, JV, Tam, CS, Heffner, LT, Varettoni, M, Palomba, ML, Shustik, C, Kastritis, E, Treon, SP, Ping, J, Hauns, B, Arango-Hisijara, I, Dimopoulos, MA, Buske, C, Tedeschi, A, Trotman, J, Garcia-Sanz, R, MacDonald, D, Leblond, V, Mahe, B, Herbaux, C, Matous, JV, Tam, CS, Heffner, LT, Varettoni, M, Palomba, ML, Shustik, C, Kastritis, E, Treon, SP, Ping, J, Hauns, B, Arango-Hisijara, I, and Dimopoulos, MA
Abstract: PURPOSE The double-blind, randomized, placebo-controlled phase III iNNOVATE study showed sustained efficacy of ibrutinib-rituximab in Waldenström’s macroglobulinemia (WM). Here, we present the final analysis from iNNOVATE. METHODS Patients had confirmed symptomatic WM, either previously untreated or previously treated; patients with prior rituximab had at least a minor response to their last rituximab-based regimen. Patients were randomly assigned to once-daily ibrutinib 420 mg plus rituximab or placebo plus rituximab (n = 75 per arm). The primary end point was progression-free survival (PFS). Secondary end points included response rate, time to next treatment, hemoglobin improvement, overall survival, and safety. RESULTS With a median follow-up of 50 (range, 0.5-63) months, median (95% CI) PFS was not reached (57.7 months to not evaluable) with ibrutinib-rituximab versus 20.3 months (13.0 to 27.6) with placebo-rituximab (hazard ratio, 0.250; P < .0001). PFS benefit was regardless of prior treatment status, MYD88 and CXCR4 mutation status, or key patient characteristics. Higher response rates (partial response or better) were observed with ibrutinib-rituximab (76% v 31% with placebo-rituximab; P < .0001) and were sustained over time. Median time to next treatment was not reached with ibrutinib-rituximab versus 18 months with placebo-rituximab. More patients receiving ibrutinib-rituximab versus placebo-rituximab had sustained hemoglobin improvement (77% v 43%; P < .0001). Median overall survival was not reached in either arm. Ibrutinib-rituximab maintained a manageable safety profile; the prevalence of grade $ 3 adverse events of clinical interest generally decreased over time. CONCLUSION In the final analysis of iNNOVATE with a median follow-up of 50 months, ibrutinib-rituximab showed ongoing superiority across clinical outcomes in patients with WM regardless of MYD88 or CXCR4 mutation status, prior treatment, and key patient characteristics.
Published: 2022

19. Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies

Author: Tam, CS, Dimopoulos, M, Garcia-Sanz, R, Trotman, J, Opat, S, Roberts, AW, Owen, R, Song, Y, Xu, W, Zhu, J, Li, J, Qiu, L, D'Sa, S, Jurczak, W, Cull, G, Marlton, P, Gottlieb, D, Munoz, J, Phillips, T, Du, C, Ji, M, Zhou, L, Guo, H, Zhu, H, Chan, WY, Cohen, A, Novotny, W, Huang, J, Tedeschi, A, Tam, CS, Dimopoulos, M, Garcia-Sanz, R, Trotman, J, Opat, S, Roberts, AW, Owen, R, Song, Y, Xu, W, Zhu, J, Li, J, Qiu, L, D'Sa, S, Jurczak, W, Cull, G, Marlton, P, Gottlieb, D, Munoz, J, Phillips, T, Du, C, Ji, M, Zhou, L, Guo, H, Zhu, H, Chan, WY, Cohen, A, Novotny, W, Huang, J, and Tedeschi, A
Abstract: Zanubrutinib is a selective Bruton tyrosine kinase (BTK) inhibitor evaluated in multiple B-cell malignancy studies. We constructed a pooled safety analysis to better understand zanubrutinib-associated treatment-emergent adverse events (TEAEs) and identify treatment-limiting toxicities. Data were pooled from 6 studies (N = 779). Assessments included type, incidence, severity, and outcome of TEAEs. Median age was 65 years; 20% were ≥75 years old. Most patients had Waldenström macroglobulinemia (33%), chronic lymphocytic leukemia/small lymphocytic lymphoma (29%), or mantle-cell lymphoma (19%). Median treatment duration was 26 months (range, 0.1-65); 16% of patients were treated for ≥3 years. Common nonhematologic TEAEs were upper respiratory tract infection (URI, 39%), rash (27%), bruising (25%), musculoskeletal pain (24%), diarrhea (23%), cough (21%), pneumonia (21%), urinary tract infection (UTI), and fatigue (15% each). Most common grade ≥3 TEAEs were pneumonia (11%), hypertension (5%), URI, UTI, sepsis, diarrhea, and musculoskeletal pain (2% each). Atrial fibrillation and major hemorrhage occurred in 3% and 4% of patients, respectively. Atrial fibrillation, hypertension, and diarrhea occurred at lower rates than those reported historically for ibrutinib. Grade ≥3 adverse events included neutropenia (23%), thrombocytopenia (8%), and anemia (8%). Serious TEAEs included pneumonia (11%), sepsis (2%), and pyrexia (2%).Treatment discontinuations and dose reductions for adverse events occurred in 10% and 8% of patients, respectively. Thirty-nine patients (4%) had fatal TEAEs, including pneumonia (n = 9), sepsis (n = 4), unspecified cause (n = 4), and multiple organ dysfunction syndrome (n = 5). This analysis demonstrates that zanubrutinib is generally well tolerated with a safety profile consistent with known BTK inhibitor toxicities; these were manageable and mostly reversible.
Published: 2022

20. Outcome of infection with omicron SARS-CoV-2 variant in patients with hematological malignancies: An EPICOVIDEHA survey report

Author: Blennow, O., Salmanton-Garcia, J., Nowak, P., Itri, F., Van Doesum, J., Lopez-Garcia, A., Farina, F., Jaksic, O., Pinczes, L. I., Bilgin, Y. M., Falces-Romero, I., Jimenez, M., Ormazabal-Velez, I., Weinbergerova, B., Dulery, R., Stojanoski, Z., Lahmer, T., Fernandez, N., Hernandez-Rivas, J. -A., Petzer, V., De Jonge, N., Glenthoj, A., De Ramon, C., Biernat, M. M., Fracchiolla, N., Aujayeb, A., Van Praet, J., Schonlein, M., Mendez, G. -A., Cattaneo, C., Guidetti, A., Sciume, M., Ammatuna, E., Cordoba, R., Garcia-Pouton, N., Grafe, S., Cabirta, A., Wolf, D., Nordlander, A., Garcia-Sanz, R., Delia, M., Berg Venemyr, C., Brones, C., Di Blasi, R., De Kort, E., Meers, S., Lamure, S., Serrano, L., Merelli, M., Coppola, N., Bergantim, R., Besson, C., Kohn, M., Petiti, J., Garcia-Vidal, C., Dargenio, M., Danion, F., Machado, M., Bailen-Almorox, R., Hoenigl, M., Dragonetti, Giulia, Chai, L. Y. A., Kho, C. S., Bonanni, Matteo, Lievin, R., Marchesi, F., Cornely, O. A., Pagano, Livio, Dragonetti G., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Blennow, O., Salmanton-Garcia, J., Nowak, P., Itri, F., Van Doesum, J., Lopez-Garcia, A., Farina, F., Jaksic, O., Pinczes, L. I., Bilgin, Y. M., Falces-Romero, I., Jimenez, M., Ormazabal-Velez, I., Weinbergerova, B., Dulery, R., Stojanoski, Z., Lahmer, T., Fernandez, N., Hernandez-Rivas, J. -A., Petzer, V., De Jonge, N., Glenthoj, A., De Ramon, C., Biernat, M. M., Fracchiolla, N., Aujayeb, A., Van Praet, J., Schonlein, M., Mendez, G. -A., Cattaneo, C., Guidetti, A., Sciume, M., Ammatuna, E., Cordoba, R., Garcia-Pouton, N., Grafe, S., Cabirta, A., Wolf, D., Nordlander, A., Garcia-Sanz, R., Delia, M., Berg Venemyr, C., Brones, C., Di Blasi, R., De Kort, E., Meers, S., Lamure, S., Serrano, L., Merelli, M., Coppola, N., Bergantim, R., Besson, C., Kohn, M., Petiti, J., Garcia-Vidal, C., Dargenio, M., Danion, F., Machado, M., Bailen-Almorox, R., Hoenigl, M., Dragonetti, Giulia, Chai, L. Y. A., Kho, C. S., Bonanni, Matteo, Lievin, R., Marchesi, F., Cornely, O. A., Pagano, Livio, Dragonetti G., Bonanni M., and Pagano L. (ORCID:0000-0001-8287-928X)
Abstract: nr
Published: 2022

21. P1115: A MULTICENTER PHASE 1/2 TRIAL OF EO2463, A MICROBIAL-DERIVED PEPTIDE THERAPEUTIC VACCINE, AS MONOTHERAPY AND IN COMBINATION WITH LENALIDOMIDE AND RITUXIMAB, FOR TREATMENT OF PATIENTS WITH INDOLENT NHL

Author: Zinzani, P. L., primary, Ansell, S. M., additional, Bosch, F., additional, Friedberg, J. W., additional, Marolleau, J. P., additional, Arcaini, L., additional, Garcia-Sanz, R., additional, Gopal, A. K., additional, Grande, C., additional, Merryman, R., additional, Pinto, A., additional, Smith, S. D., additional, Villasboas, J. C., additional, Wallace, D., additional, Fagerberg, J., additional, Magalhaes, J. G., additional, and Armand, P., additional
Published: 2022
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22. P1083: BRENTUXIMAB VEDOTIN, ETOPOSIDE, SOLUMEDROL, HIGH DOSE ARA-C & PLATINUM FOLLOWED BY HDT & APBSCT FOR REFRACTORY/RELAPSED HODGKIN LYMPHOMA PATIENTS: LONG-TERM RESULTS OF THE GELTAMO GROUP BRESHAP STUDY

Author: Garcia-Sanz, R., primary, Martínez, C., additional, De la Cruz, F., additional, González, A. P., additional, Rodríguez, A., additional, Sánchez-González, B., additional, Domingo-Domenech, E., additional, Moreno, M., additional, López, J., additional, Piñana, J. L., additional, Bastos, M., additional, Canales, M., additional, Gutiérrez, A., additional, Rodríguez-Salazar, M. J., additional, Navarro, A., additional, and Sureda, A., additional
Published: 2022
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23. P1161: ASPEN: LONG-TERM FOLLOW-UP RESULTS OF A PHASE 3 RANDOMIZED TRIAL OF ZANUBRUTINIB (ZANU) VS IBRUTINIB (IBR) IN PATIENTS (PTS) WITH WALDENSTRÖM MACROGLOBULINEMIA (WM)

Author: Dimopoulos, M., primary, Opat, S., additional, D’Sa, S., additional, Jurczak, W., additional, Lee, H.-P., additional, Cull, G., additional, Owen, R. G., additional, Marlton, P., additional, Wahlin, B. E., additional, Garcia-Sanz, R., additional, McCarthy, H., additional, Mulligan, S., additional, Tedeschi, A., additional, Castillo, J. J., additional, Czyz, J., additional, Fernandez De Larrea Rodriguez, C., additional, Belada, D., additional, Libby, E., additional, Matous, J., additional, Motta, M., additional, Siddiqi, T., additional, Tani, M., additional, Trneny, M., additional, Minnema, M., additional, Buske, C., additional, Leblond, V., additional, Treon, S. P., additional, Trotman, J., additional, Chan, W. Y., additional, Schneider, J., additional, Allewelt, H., additional, Cohen, A., additional, Huang, J., additional, and Tam, C. S., additional
Published: 2022
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24. Booster effect after SARS-CoV-2 vaccination in immunocompromised hematology patients with prior COVID-19

Author: Pinana J, Garcia-Sanz R, Martino R, Garcia-Rao M, Martin-Martin G, Risco-Galvez I, Tormo M, Martinez-Barranco P, Marcos-Corrales S, Calabuig M, Conesa V, Teruel A, Ruiz-Perez S, Solano C, Navarro D, Cedillo A, Sureda A, and Infectious Complications Subc
Published: 2022

25. Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies

Author: Tam, C.S. Dimopoulos, M. Garcia-Sanz, R. Trotman, J. Opat, S. Roberts, A.W. Owen, R. Song, Y. Xu, W. Zhu, J. Li, J. Qiu, L. D’Sa, S. Jurczak, W. Cull, G. Marlton, P. Gottlieb, D. Munoz, J. Phillips, T. Du, C. Ji, M. Zhou, L. Guo, H. Zhu, H. Chan, W.Y. Cohen, A. Novotny, W. Huang, J. Tedeschi, A.
Abstract: Zanubrutinib is a selective Bruton tyrosine kinase (BTK) inhibitor evaluated in multiple B-cell malignancy studies. We constructed a pooled safety analysis to better understand zanubrutinib-associated treatment-emergent adverse events (TEAEs) and identify treatment-limiting toxicities. Data were pooled from 6 studies (N 5 779). Assessments included type, incidence, severity, and outcome of TEAEs. Median age was 65 years; 20% were $75 years old. Most patients had Waldenstrom € macroglobulinemia (33%), chronic lymphocytic leukemia/small lymphocytic lymphoma (29%), or mantle-cell lymphoma (19%). Median treatment duration was 26 months (range, 0.1-65); 16% of patients were treated for $3 years. Common nonhematologic TEAEs were upper respiratory tract infection (URI, 39%), rash (27%), bruising (25%), musculoskeletal pain (24%), diarrhea (23%), cough (21%), pneumonia (21%), urinary tract infection (UTI), and fatigue (15% each). Most common grade $3 TEAEs were pneumonia (11%), hypertension (5%), URI, UTI, sepsis, diarrhea, and musculoskeletal pain (2% each). Atrial fibrillation and major hemorrhage occurred in 3% and 4% of patients, respectively. Atrial fibrillation, hypertension, and diarrhea occurred at lower rates than those reported historically for ibrutinib. Grade $3 adverse events included neutropenia (23%), thrombocytopenia (8%), and anemia (8%). Serious TEAEs included pneumonia (11%), sepsis (2%), and pyrexia (2%).Treatment discontinuations and dose reductions for adverse events occurred in 10% and 8% of patients, respectively. Thirty-nine patients (4%) had fatal TEAEs, including pneumonia (n 5 9), sepsis (n 5 4), unspecified cause (n 5 4), and multiple organ dysfunction syndrome (n 5 5). This analysis demonstrates that zanubrutinib is generally well tolerated with a safety profile consistent with known BTK inhibitor toxicities; these were manageable and mostly reversible. © 2022 by The American Society of Hematology.
Published: 2022

26. Spanish Society of Hematology and Hemotherapy expert consensus opinion for SARS-CoV-2 vaccination in onco-hematological patients

Author: Pinana, JL, Vazquez, L, Martino, R, de la Camara, R, Sureda, A, Rodriguez-Veiga, R, Garrido, A, Sierra, J, Ribera, JM, Torrent, A, Mateos, MV, de la Rubia, J, Tormo, M, Diez-Campelo, M, Garcia-Gutierrez, V, Alvarez-Larran, A, Sancho, JM, MartinGarcia-Sancho, A, Yanez, L, Simon, JAP, Barba, P, Abrisqueta, P, Alvarez-Twose, I, Bonanad, S, Lecumberri, R, Ruiz-Camps, I, Navarro, D, Hernandez-Rivas, JA, Cedillo, A, Garcia-Sanz, R, and Bosch, F
Subjects: vaccination consensus, onco-hematology, allogeneic stem cell transplantation, SARS-CoV-2 vaccine, myeloproliferative neoplasm, COVID-19, lymphoma, myelodisplastic syndrome, acute leukemia, stem cell transplantation
Abstract: In the midst of the COVID-19 pandemic, different vaccines in front of SARS-CoV-2 have been approved and administered in different vulnerable populations. As patients with cancer were excluded from pivotal trials of vaccination, little is known on their immunogenic response to these vaccines, particularly in patients with severely impaired immune system. In response to that uncertainty, the Spanish Society of Hematology and Hemotherapy launched an initiative aimed to provide recommendations for vaccination of the main hematological conditions. This document is based on the available information on COVID-19 outcomes, prior knowledge on vaccination in hematological patients, recent published data on serological response in oncohematological patients and expert opinions. New information about SARS-CoV-2 vaccination will be gathered in the near future, providing new scientific grounds to delineate the most adequate management of vaccination in patients with hematological diseases. The current limited data on SARS-CoV-2 vaccines in hematological patients represents a major limitation of this expert consensus opinion. In fact, the speed in which this field evolves may reduce their validity in the near future.
Published: 2022

27. A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper

Author: Zozaya, N, Villaseca, J, Abdalla, F, Calleja, MA, Diez-Martin, JL, Estevez, J, Garcia-Sanz, R, Martinez-Lopez, J, Sierra, J, Vera, R, and Hidalgo-Vega, A
Subjects: Spain, Advanced therapies, CAR-T therapy, National health system
Abstract: CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.
Published: 2022

28. Report of Consensus Panel 4 from the 11thInternational Workshop on Waldenstrom's Macroglobulinemia on Diagnostic and Response Criteria

Author: Treon, SP, Tedeschi, A, San-Miguel, J, Garcia-Sanz, R, Anderson, KC, Kimby, E, Minnema, MC, Benevolo, G, Qiu, L, Yi, S, Terpos, E, Tam, CS, Castillo, JJ, Morel, P, Dimopoulos, M, and Owen, RG
Abstract: Consensus Panel 4 (CP4) of the 11thInternational Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) was tasked with reviewing the current criteria for diagnosis and response assessment. Since the initial consensus reports of the 2ndInternational Workshop, there have been updates in the understanding of the mutational landscape of IgM related diseases, including the discovery and prevalence of MYD88 and CXCR4 mutations; an improved recognition of disease related morbidities attributed to monoclonal IgM and tumor infiltration; and a better understanding of response assessment based on multiple, prospective trials that have evaluated diverse agents in WM. The key recommendations from IWWM-11 CP4 included: i) re-affirmation of IWWM-2 consensus panel recommendations that arbitrary values for laboratory parameters such as minimal IgM level or BM infiltration should not be used to distinguish WM from IgM MGUS; ii) delineation of IgM MGUS into two subclasses including a subtype characterized by clonal plasma cells and MYD88 wild-type, and the other by presence of monotypic or monoclonal B cells which may carry the MYD88 mutation; and iii) recognition of “simplified” response assessments that use serum IgM only for determining partial and very good partial responses (simplified IWWM-6/new IWWM-11 response criteria). Guidance on response determination for suspected IgM flare and IgM rebound related to treatment, as well as extramedullary disease assessment was also updated and included in this report.
Published: 2023
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29. Report of Consensus Panel 3 from the 11thInternational Workshop on Waldenström's Macroglobulinemia: Recommendations for Molecular Diagnosis in Waldenström's Macroglobulinemia

Author: Garcia-Sanz, R, Varettoni, M, Jiménez, C, Ferrero, S, Poulain, S, San-Miguel, JF, Guerrera, ML, Drandi, D, Bagratuni, T, McMaster, M, Roccaro, AM, Roos-Weil, D, Leiba, M, Li, Y, Qiu, L, Hou, J, De Larrea, C Fernandez, Castillo, JJ, Dimopoulos, M, Owen, RG, Treon, SP, and Hunter, ZR
Abstract: Apart from the MYD88L265Pmutation, extensive information exists on the molecular mechanisms in Waldenström's Macroglobulinemia and its potential utility in the diagnosis and treatment tailoring. However, no consensus recommendations are yet available. Consensus Panel 3 (CP3) of the 11thInternational Workshop on Waldenström's Macroglobulinemia (IWWM-11) was tasked with reviewing the current molecular necessities and best way to access the minimum data required for a correct diagnosis and monitoring. Key recommendations from IWWM-11 CP3 included: 1) molecular studies are warranted for patients in whom therapy is going to be started; such studies should also be done in those whose bone marrow (BM) material is sampled based on clinical issues; 2) molecular studies considered essential for these situations are those that clarify the status of 6q and 17p chromosomes, and MYD88, CXCR4, and TP53genes. These tests in other situations, and/or other tests, are considered optional; 3) independently of the use of more sensitive and/or specific techniques, the minimum requirements are Allele Specific Polymerase Chain Reaction for MYD88L265Pand CXCR4S338Xusing whole BM, and Fluorescence in situ hybridization for 6q and 17p and sequencing for CXCR4and TP53using CD19+ enriched BM; 4) these requirements refer to all patients; therefore, sample should be sent to specialized centers.
Published: 2023
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30. Report of Consensus Panel 7 from the 11thInternational Workshop on Waldenström Macroglobulinemia on Priorities for Novel Clinical Trials.

Author: Tam, CS, Kapoor, P, Castillo, JJ, Buske, C, Ansell, SM, Branagan, AR, Kimby, E, Li, Y, Palomba, ML, Qiu, L, Shadman, M, Abeykoon, JP, Sarosiek, S, Vos, JMI, Yi, S, Stephens, D, Roos-Weil, D, Roccaro, AM, Morel, P, Munshi, NC, Anderson, KC, San-Miguel, J, Garcia-Sanz, R, Dimopoulos, MA, Treon, SP, and Kersten, MJ.
Abstract: Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have impacted the development of effective novel agents and improved our knowledge of how the genomic background of WM may influence selection of therapy. Consensus Panel 7 (CP7) of the 11thInternational Workshop on WM was convened to examine the current generation of completed and ongoing clinical trials involving novel agents, consider updated data on WM genomics, and make recommendations on the design and prioritization of future clinical trials. CP7 considers limited duration and novel-novel agent combinations to be the priority for the next generation of clinical trials. Evaluation of MYD88, CXCR4and TP53at baseline in the context of clinical trials is crucial. The common chemoimmunotherapy backbones, bendamustine-rituximab (BR) and dexamethasone, rituximab and cyclophosphamide (DRC), may be considered standard-of-care for the frontline comparative studies. Key unanswered questions include the definition of frailty in WM; the importance of attaining a very good partial response or better (≥VGPR), within stipulated time frame, in determining survival outcomes; and the optimal treatment of WM populations with special needs
Published: 2023
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31. Dexamethasone treatment for COVID-19 is related to increased mortality in hematologic malignancy patients: results from the EPICOVIDEHA registry.

Author: Aiello TF, Salmanton-Garcia J, Marchesi F, Weinbergerova B, Glenthoj A, Van Praet J, Farina F, Davila-Valls J, Martin-Perez S, El-Ashwah S, Schonlein M, Falces-Romero I, Labrador J, Sili U, Buquicchio C, Vena A, Plantefeve G, Petzer V, Biernat MM, Lahmer T, Espigado I, Van Doesum J, Blennow O, Piukovics K, Tascini C, Samarkos M, Bilgin YM, Fianchi L, Itri F, Valković T, Fracchiolla NS, Dargenio M, Jimenez M, Magyari F, Lopez-Garcia A, Prezioso L, Čolović N, Shumilov E, Abu-Zeinah G, Krekeler C, Lavilla-Rubira E, Papa MV, Gonzalez-Lopez TJ, Pinczes LI, Demirkan F, Ali N, Besson C, Fouquet G, Romano A, Hernandez-Rivas JA, Del Principe MI, Aujayeb A, Merelli M, Lamure S, De Almeida JM, Da Silva MG, Eisa N, Meletiadis J, Rinaldi I, Finizio O, Jaksic O, Delia M, Nizamuddin S, Marchetti M, Ijaz M, Machado M, Bailen-Almorox R, Čerňan M, Coppola N, Gavriilaki E, Cattaneo C, Groh A, Stojanoski Z, Erben N, Pantic N, Mendez GA, Di Blasi R, Meers S, De Ramon C, Bahr NC, Emarah Z, Varricchio G, Cvetanoski M, Garcia-Sanz R, Mitrovic M, Lievin R, Hanakova M, Račil Z, Vehreschild M, Tragiannidis A, Rodrigues RN, Garcia-Bordallo D, Cordoba R, Cabirta A, Nordlander A, Ammatuna E, Arellano E, Wolf D, Prin R, Limongelli A, Bavastro M, Colak GM, Grafe S, Hersby DS, Rahimli L, Cornely OA, Garcia-Vidal C, Pagano L, and Study Group E
Subjects: Humans, Male, Female, Aged, Middle Aged, Adult, Aged, 80 and over, Dexamethasone therapeutic use, Hematologic Neoplasms mortality, Hematologic Neoplasms drug therapy, Registries, COVID-19 mortality, COVID-19 complications, SARS-CoV-2 isolation & purification, COVID-19 Drug Treatment
Published: 2024
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32. Health-related quality of life in patients with Waldenström macroglobulinemia: results from the ASPEN trial.

Author: Tedeschi A, Tam CS, Owen RG, Buske C, Leblond V, Dimopoulos M, Garcia-Sanz R, Castillo JJ, Trotman J, Treon SP, Yang K, Tang B, Allewelt H, Patel S, Chan WY, Cohen A, Chen S, and Barnes G
Subjects: Humans, Male, Female, Aged, Middle Aged, Myeloid Differentiation Factor 88 genetics, Patient Reported Outcome Measures, Aged, 80 and over, Treatment Outcome, Mutation, Adult, Waldenstrom Macroglobulinemia drug therapy, Quality of Life, Piperidines therapeutic use, Pyrimidines therapeutic use, Pyrazoles therapeutic use, Adenine analogs & derivatives, Adenine therapeutic use
Abstract: Aim ASPEN is a randomized, open-label, Phase III study comparing zanubrutinib and ibrutinib in patients with Waldenström macroglobulinemia (WM). Materials & methods: Patient-reported outcomes were exploratory end points assessed using the EORTC QLQ-C30 and EQ-5D-5L VAS scores. Results: Overall, 201 patients (102 zanubrutinib; 99 ibrutinib) were enrolled. Clinically meaningful differences were observed in diarrhea and nausea/vomiting in both the intent-to-treat population and in patients attaining very good partial response (VGPR) in earlier cycles of treatment, as well as in long-term physical functioning and fatigue in patients achieving VGPR. Conclusion: Treatment with zanubrutinib was associated with greater improvements in health-related quality of life compared with ibrutinib in patients with WM and MYD88 mutations. Clinical Trial Registration: NCT03053440 (ClinicalTrials.gov).
Published: 2024
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33. Zanubrutinib Versus Ibrutinib in Symptomatic Waldenström Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study.

Author: Dimopoulos MA, Opat S, D'Sa S, Jurczak W, Lee HP, Cull G, Owen RG, Marlton P, Wahlin BE, Garcia-Sanz R, McCarthy H, Mulligan S, Tedeschi A, Castillo JJ, Czyz J, Fernández de Larrea C, Belada D, Libby E, Matous J, Motta M, Siddiqi T, Tani M, Trněný M, Minnema MC, Buske C, Leblond V, Treon SP, Trotman J, Chan WY, Schneider J, Allewelt H, Patel S, Cohen A, and Tam CS
Subjects: Humans, Piperidines therapeutic use, Pyrimidines adverse effects, Waldenstrom Macroglobulinemia drug therapy, Waldenstrom Macroglobulinemia genetics
Abstract: The phase III ASPEN study demonstrated the comparable efficacy and improved safety of zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia (WM). Here, we report long-term follow-up outcomes from ASPEN. The primary end point was the sum of very good partial response (VGPR) + complete response (CR) rates; secondary and exploratory end points were also reported. Cohort 1 comprised 201 patients (myeloid differentiation primary response 88-mutant WM: 102 receiving zanubrutinib; 99 receiving ibrutinib); cohort 2 comprised 28 patients (myeloid differentiation primary response 88 wild-type WM: 28 zanubrutinib; 26 efficacy evaluable). At 44.4-month median follow-up, VGPR + CR rates were 36.3% with zanubrutinib versus 25.3% with ibrutinib in cohort 1 and 30.8% with one CR in cohort 2. In patients with CXC motif chemokine receptor 4 mutation, VGPR + CR rates were 21.2% with zanubrutinib versus 10.0% with ibrutinib (cohort 1). Median progression-free survival and overall survival were not reached. Any-grade adverse events (AEs) of diarrhea (34.7% v 22.8%), muscle spasms (28.6% v 11.9%), hypertension (25.5% v 14.9%), atrial fibrillation/flutter (23.5% v 7.9%), and pneumonia (18.4% v 5.0%) were more common with ibrutinib versus zanubrutinib; neutropenia (20.4% v 34.7%) was less common with ibrutinib versus zanubrutinib (cohort 1). Zanubrutinib was associated with lower risk of AE-related treatment discontinuation. Overall, these findings confirm the long-term response quality and tolerability associated with zanubrutinib.
Published: 2023
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34. Molecular remission is an independent predictor of progression-free survival in patients with Waldenström macroglobulinemia treated with chemo-immunotherapy: Results from the FIL_BIOWM study.

Author: Varettoni M, Zibellini S, Merli M, Drandi D, Jiménez C, Furlan D, Ferretti VV, Fabbri N, Dogliotti I, Varraso C, Ferrante M, Cappello E, Peri V, Cavalloni C, Borriero M, Facchetti GV, Ferrero S, Arcaini L, and Garcia-Sanz R
Subjects: Humans, Progression-Free Survival, Mutation, Signal Transduction, Waldenstrom Macroglobulinemia drug therapy
Published: 2023
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35. Bortezomib-Dexamethasone, Rituximab, and Cyclophosphamide as First-Line Treatment for Waldenström's Macroglobulinemia: A Prospectively Randomized Trial of the European Consortium for Waldenström's Macroglobulinemia.

Author: Buske C, Dimopoulos MA, Grunenberg A, Kastritis E, Tomowiak C, Mahé B, Troussard X, Hajek R, Viardot A, Tournilhac O, Aurran T, Lepretre S, Zerazhi H, Hivert B, Leblond V, de Guibert S, Brandefors L, Garcia-Sanz R, Gomes da Silva M, Kimby E, Schmelzle B, Kaszynski D, Dreyhaupt J, Muche R, and Morel P
Subjects: Humans, Rituximab, Bortezomib adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cyclophosphamide, Dexamethasone, Waldenstrom Macroglobulinemia drug therapy
Abstract: Purpose: Rituximab/chemotherapy is a cornerstone of treatment for Waldenström's macroglobulinemia (WM). In addition, bortezomib has shown significant activity in WM. This study evaluated the efficacy and safety of dexamethasone, rituximab, and cyclophosphamide (DRC) as first-line treatment in WM., Methods: In this European study, treatment-naïve patients were randomly assigned to DRC or bortezomib-DRC B-DRC for six cycles. The primary end point was progression-free survival. Secondary end points included response rates, overall survival, and safety., Results: Two hundred four patients were registered. After a median follow-up of 27.5 months, the estimated 24-month progression-free survival was 80.6% (95% CI, 69.5 to 88.0) for B-DRC and 72.8% (95% CI, 61.3 to 81.3) for DRC ( P = .32). At the end of treatment, B-DRC and DRC induced major responses in 80.6% versus 69.9% and a complete response/very good partial response in 17.2% versus 9.6% of patients, respectively. The median time to first response was shorter for B-DRC with 3.0 (95% CI, 2.8 to 3.2) versus 5.5 (95% CI, 2.9 to 5.8) months for DRC. This resulted in higher major response rates (57.0% v 32.5%; P < .01) after three cycles of B-DRC compared with DRC. At best response, the complete response/very good partial response increased to 32.6% for B-DRC. Both treatments were well tolerated: grade ≥ 3 adverse events occurred in 49.2% of all patients (B-DRC, 49.5%; DRC, 49.0%). Peripheral sensory neuropathy grade 3 occurred in two patients treated with B-DRC and in none with DRC., Conclusion: This large randomized study illustrates that B-DRC is highly effective and well tolerated in WM. The data demonstrate that fixed duration immunochemotherapy remains an important pillar in the clinical management of WM.
Published: 2023
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36. Report of consensus panel 1 from the 11 th International Workshop on Waldenstrom's Macroglobulinemia on management of symptomatic, treatment-naïve patients.

Author: Buske C, Castillo JJ, Abeykoon JP, Advani R, Arulogun SO, Branagan AR, Cao X, D'Sa S, Hou J, Kapoor P, Kastritis E, Kersten MJ, LeBlond V, Leiba M, Matous JV, Paludo J, Qiu L, Tam CS, Tedeschi A, Thomas SK, Tohidi-Esfahani I, Varettoni M, Vos JM, Garcia-Sanz R, San-Miguel J, Dimopoulos MA, Treon SP, and Trotman J
Subjects: Humans, Rituximab therapeutic use, Consensus, Prospective Studies, Bendamustine Hydrochloride therapeutic use, Waldenstrom Macroglobulinemia drug therapy, Waldenstrom Macroglobulinemia genetics, Waldenstrom Macroglobulinemia diagnosis, Immunoglobulin Light-chain Amyloidosis
Abstract: Consensus Panel 1 (CP1) of the 11 th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) was tasked with updating guidelines for the management of symptomatic, treatment-naïve patients with WM. The panel reiterated that watchful waiting remains the gold standard for asymptomatic patients without critically elevated IgM or compromised hematopoietic function. For first-line treatment, chemoimmunotherapy (CIT) regimens such as dexamethasone, cyclophosphamide, rituximab (DRC), or bendamustine, rituximab (Benda-R) continue to play a central role in managing WM, as they are effective, of fixed duration, generally well-tolerated, and affordable. Covalent BTK inhibitors (cBTKi) offer a continuous, generally well-tolerated alternative for the primary treatment of WM patients, particularly those unsuitable for CIT. In a Phase III randomized trial updated at IWWM-11, the second-generation cBTKi, zanubrutinib, was less toxic than ibrutinib and induced deeper remissions, thus categorizing zanubrutinib as a suitable treatment option in WM. While the overall findings of a prospective, randomized trial updated at IWWM-11 did not show superiority of fixed duration rituximab maintenance over observation following attainment of a major response to Benda-R induction, a subset analysis showed benefit in patients >65 years and those with a high IPPSWM score. Whenever possible, the mutational status of MYD88 and CXCR4 should be determined before treatment initiation, as alterations in these 2 genes predict sensitivity towards cBTKi activity. Treatment approaches for WM-associated cryoglobulins, cold agglutinins, AL amyloidosis, Bing-Neel syndrome (BNS), peripheral neuropathy, and hyperviscosity syndrome follow the common principle of reducing tumor and abnormal protein burden rapidly and deeply to improve symptoms. In BNS, ibrutinib can be highly active and produce durable responses. In contrast, cBTKi are not recommended for treating AL amyloidosis. The panel emphasized that continuous improvement of treatment options for symptomatic, treatment-naïve WM patients critically depends on the participation of patients in clinical trials, whenever possible., (Copyright © 2023. Published by Elsevier Inc.)
Published: 2023
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37. Report of Consensus Panel 6 from the 11 th International Workshop on Waldenström's Macroglobulinemia on Management of Waldenström's Macroglobulinemia Related Amyloidosis.

Author: Merlini G, Sarosiek S, Benevolo G, Cao X, Dimopoulos M, Garcia-Sanz R, Gatt ME, Fernandez de Larrea C, San-Miguel J, Treon SP, and Minnema MC
Subjects: Humans, Consensus, Waldenstrom Macroglobulinemia complications, Waldenstrom Macroglobulinemia diagnosis, Waldenstrom Macroglobulinemia therapy, Immunoglobulin Light-chain Amyloidosis complications, Immunoglobulin Light-chain Amyloidosis diagnosis, Immunoglobulin Light-chain Amyloidosis therapy, Amyloid Neuropathies, Familial complications
Abstract: Consensus Panel 6 (CP6) of the 11th International Workshop on Waldenström's Macroglobulinemia (IWWM-11) was tasked with reviewing the state of the art for diagnosis, prognosis, and therapy of AL amyloidosis associated with Waldenström macroglobulinemia (WM). Since significant advances have been made in the management of AL amyloidosis an update for this rare disease associated with WM was necessary. The key recommendations from IWWM-11 CP6 included: (1) The need to improve the diagnostic process by recognizing red flags and using biomarkers and imaging; (2) The essential tests for appropriate workup; (3) The diagnostic flowchart, including mandatory amyloid typing, that improves the differential diagnosis with transthyretin amyloidosis; (4) Criteria for therapy response assessment; (5) State of the art of the treatment including therapy of wild type transthyretin amyloidosis associated with WM., Competing Interests: Declaration of Competing Interest GM has no disclosures. MCM received research funding from Beigene, and consulting fees from BMS, GSK, Jansen Cilag, and CDR life. SRS received research funding and/or consulting fees from Beigene, Cellectar Biosciences, and ADC Therapeutics. GB declares participation on advisory boards and speakers bureau for Janssen-Cilag, Bristol Myers Squibb and Novartis. SPT received research funding, and/or consulting fees from Abbvie/Pharmacyclics Inc., Janssen Oncology Inc., Beigene Inc., Eli Lilly Pharmaceuticals, and Bristol Myers Squibb. CFL reports: consultancy: Janssen, BeiGene, BMS, Amgen, GSK; reserach grants: Janssen, Amgen, BMS; Advisory: BeiGene, Janssen, Amgen, BMS, GSK. JSM declares participation on advisory boards and consulting services, on behalf of my Institution, for Abbvie, Amgen, BMS, Celgene, GSK, Haemalogix, Janssen-Cilag, Karyopharm, MSD, Novartis, Pfizer, Takeda, Regeneron, Roche, Sanofi, and SecuraBio. MD received honoraria from Amgen, Bristol Myers Squibb, GSK, Janssen, Beigene Inc, Sanofi and Takeda. RGS declares honoraria from Amgen, Takeda, Janssen, Incyte, Astellas, BeiGene, AstraZeneca, Pfizer; and research funding from Novartis, Gilead, Astellas, Janssen; and participation in advisory boards for Amgen, Pharmacyclics, Takeda. XC reports no disclosures. MG reports no disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)
Published: 2023
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38. A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk.

Author: Dicanio M, Giaccherini M, Clay-Gilmour A, Macauda A, Sainz J, Machiela MJ, Rybicka-Ramos M, Norman AD, Tyczyńska A, Chanock SJ, Barington T, Kumar SK, Bhatti P, Cozen W, Brown EE, Suska A, Haastrup EK, Orlowski RZ, Dudziński M, Garcia-Sanz R, Kruszewski M, Martinez-Lopez J, Beider K, Iskierka-Jazdzewska E, Pelosini M, Berndt SI, Raźny M, Jamroziak K, Rajkumar SV, Jurczyszyn A, Vangsted AJ, Collado PG, Vogel U, Hofmann JN, Petrini M, Butrym A, Slager SL, Ziv E, Subocz E, Giles GG, Andersen NF, Mazur G, Watek M, Lesueur F, Hildebrandt MAT, Zawirska D, Ebbesen LH, Marques H, Gemignani F, Dumontet C, Várkonyi J, Buda G, Nagler A, Druzd-Sitek A, Wu X, Kadar K, Camp NJ, Grzasko N, Waller RG, Vachon C, Canzian F, and Campa D
Subjects: Humans, Oncogenes, Alleles, Phenotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Predisposition to Disease, HSP40 Heat-Shock Proteins genetics, DNA-Binding Proteins genetics, RNA-Binding Proteins, Multiple Myeloma epidemiology, Multiple Myeloma genetics
Abstract: Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10 -8 ) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13-1.32, P = 4.81 × 10 -7 ). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Published: 2023
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39. NGS-Based Molecular Karyotyping of Multiple Myeloma: Results from the GEM12 Clinical Trial.

Author: Rosa-Rosa JM, Cuenca I, Medina A, Vázquez I, Sánchez-delaCruz A, Buenache N, Sánchez R, Jiménez C, Rosiñol L, Gutiérrez NC, Ruiz-Heredia Y, Barrio S, Oriol A, Martin-Ramos ML, Blanchard MJ, Ayala R, Ríos-Tamayo R, Sureda A, Hernández MT, de la Rubia J, Alkorta-Aranburu G, Agirre X, Bladé J, Mateos MV, Lahuerta JJ, San-Miguel JF, Calasanz MJ, Garcia-Sanz R, and Martínez-Lopez J
Abstract: Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival ( p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes ( p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients.
Published: 2022
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40. Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients.

Author: Piñana JL, Rodríguez-Belenguer P, Caballero D, Martino R, Lopez-Corral L, Terol MJ, Vazquez L, Calabuig M, Sanz-Linares G, Marin-Jimenez F, Alonso C, Montoro J, Ferrer E, Facal A, Pascual MJ, Rodriguez-Fernandez A, Olave MT, Cascales-Hernandez A, Gago B, Hernández-Rivas JÁ, Villalon L, Corona M, Roldán-Pérez A, Ribes-Amoros J, González-Santillana C, Garcia-Sanz R, Navarro D, Serrano-López AJ, Cedillo Á, Soria-Olivas E, Sureda A, and Solano C
Subjects: Antibodies, Monoclonal, Antibodies, Viral, BNT162 Vaccine, COVID-19 Vaccines, Early Detection of Cancer, Humans, SARS-CoV-2, Vaccination, Antineoplastic Agents, COVID-19 diagnosis, COVID-19 prevention & control
Abstract: Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Published: 2022
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41. High frequency of central nervous system involvement in transformed Waldenström macroglobulinemia.

Author: Durot E, Kanagaratnam L, Zanwar S, Toussaint E, Kastritis E, D'Sa S, Alcoceba M, Tomowiak C, Hivert B, Protin C, Abeykoon JP, Vos JMI, Michallet AS, Rodier C, Dupuis J, Leprêtre S, Merabet F, Roussel X, Zini JM, Regny C, Patel A, Morel P, Roos-Weil D, Treon SP, Dimopoulos MA, Garcia-Sanz R, Kapoor P, Castillo JJ, and Delmer AJ
Subjects: Central Nervous System, Humans, Waldenstrom Macroglobulinemia
Published: 2022
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42. Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies.

Author: Tam CS, Dimopoulos M, Garcia-Sanz R, Trotman J, Opat S, Roberts AW, Owen R, Song Y, Xu W, Zhu J, Li J, Qiu L, D'Sa S, Jurczak W, Cull G, Marlton P, Gottlieb D, Munoz J, Phillips T, Du C, Ji M, Zhou L, Guo H, Zhu H, Chan WY, Cohen A, Novotny W, Huang J, and Tedeschi A
Subjects: Adult, Aged, Diarrhea chemically induced, Humans, Piperidines, Pyrazoles, Pyrimidines, Atrial Fibrillation, Hypertension, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Lymphoma, B-Cell, Lymphoma, Follicular, Musculoskeletal Pain, Pneumonia, Sepsis
Abstract: Zanubrutinib is a selective Bruton tyrosine kinase (BTK) inhibitor evaluated in multiple B-cell malignancy studies. We constructed a pooled safety analysis to better understand zanubrutinib-associated treatment-emergent adverse events (TEAEs) and identify treatment-limiting toxicities. Data were pooled from 6 studies (N = 779). Assessments included type, incidence, severity, and outcome of TEAEs. Median age was 65 years; 20% were ≥75 years old. Most patients had Waldenström macroglobulinemia (33%), chronic lymphocytic leukemia/small lymphocytic lymphoma (29%), or mantle-cell lymphoma (19%). Median treatment duration was 26 months (range, 0.1-65); 16% of patients were treated for ≥3 years. Common nonhematologic TEAEs were upper respiratory tract infection (URI, 39%), rash (27%), bruising (25%), musculoskeletal pain (24%), diarrhea (23%), cough (21%), pneumonia (21%), urinary tract infection (UTI), and fatigue (15% each). Most common grade ≥3 TEAEs were pneumonia (11%), hypertension (5%), URI, UTI, sepsis, diarrhea, and musculoskeletal pain (2% each). Atrial fibrillation and major hemorrhage occurred in 3% and 4% of patients, respectively. Atrial fibrillation, hypertension, and diarrhea occurred at lower rates than those reported historically for ibrutinib. Grade ≥3 adverse events included neutropenia (23%), thrombocytopenia (8%), and anemia (8%). Serious TEAEs included pneumonia (11%), sepsis (2%), and pyrexia (2%).Treatment discontinuations and dose reductions for adverse events occurred in 10% and 8% of patients, respectively. Thirty-nine patients (4%) had fatal TEAEs, including pneumonia (n = 9), sepsis (n = 4), unspecified cause (n = 4), and multiple organ dysfunction syndrome (n = 5). This analysis demonstrates that zanubrutinib is generally well tolerated with a safety profile consistent with known BTK inhibitor toxicities; these were manageable and mostly reversible., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Published: 2022
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43. Preneoplastic somatic mutations including MYD88 L265P in lymphoplasmacytic lymphoma.

Author: Rodriguez S, Celay J, Goicoechea I, Jimenez C, Botta C, Garcia-Barchino MJ, Garces JJ, Larrayoz M, Santos S, Alignani D, Vilas-Zornoza A, Perez C, Garate S, Sarvide S, Lopez A, Reinhardt HC, Carrasco YR, Sanchez-Garcia I, Larrayoz MJ, Calasanz MJ, Panizo C, Prosper F, Lamo-Espinosa JM, Motta M, Tucci A, Sacco A, Gentile M, Duarte S, Vitoria H, Geraldes C, Paiva A, Puig N, Garcia-Sanz R, Roccaro AM, Fuerte G, San Miguel JF, Martinez-Climent JA, and Paiva B
Subjects: Aged, Animals, Humans, Mice, Mutation, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 metabolism, Lymphoma, Lymphoma, B-Cell metabolism, Waldenstrom Macroglobulinemia diagnosis, Waldenstrom Macroglobulinemia genetics, Waldenstrom Macroglobulinemia pathology
Abstract: Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88 . We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88 L265P in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88 L265P is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas.
Published: 2022
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44. Booster effect after SARS-CoV-2 vaccination in immunocompromised hematology patients with prior COVID-19.

Author: Piñana JL, Garcia-Sanz R, Martino R, Garcia-Roa M, Martin-Martin GA, Risco-Gálvez I, Tormo M, Martinez-Barranco P, Marcos-Corrales S, Calabuig M, Conesa V, Teruel A, Ruiz-Pérez S, Solano C, Navarro D, Cedillo Á, and Sureda A
Subjects: COVID-19 Vaccines, Humans, SARS-CoV-2, Vaccination, COVID-19, Hematology
Published: 2022
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