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2. Secondary infections worsen the outcome of COVID-19 in patients with hematological malignancies: A report from the ITA-HEMA-COV

Author

Zappasodi, P, Cattaneo, C, Ferretti, V, Mina, R, Ferreri, A, Merli, F, Oberti, M, Krampera, M, Romano, A, Zerbi, C, Ferrari, J, Cavo, M, Marco Salvini, M, Bertù, L, Fracchiolla, N, Marchesi, F, Massaia, M, Marasco, V, Cairoli, R, Scattolin, A, Vannucchi, A, Gambacorti-Passerini, C, Musto, P, Gherlinzoni, F, Cuneo, A, Pinto, A, Trentin, L, Bocchia, M, Galimberti, Coviello, E, Mc, Morotti, A, Falini, B, Turrin, M, Tafuri, A, Billio, A, Gentile, M, Lemoli, M, 37, Venditti, A, Della Porta, M, Lanza, F, Rigacci, L, Tosi, P, Mohamed, S, Corso, A, Luppi, M, Giuliani, N, Busca, A, Pagano, L, Bruno, R, Grossi, P, Corradini, P, Passamonti, F, Arcaini, L, Zappasodi P, Cattaneo C, Ferretti V, Mina R, Ferreri AJ, Merli F, Oberti M, Krampera M, Romano A, Zerbi C, Ferrari J, Cavo M, Marco Salvini M, Bertù L, Fracchiolla N, Marchesi F, Massaia M, Marasco V, Cairoli R, Scattolin AM, Vannucchi AM, Gambacorti-Passerini C, Musto P, Gherlinzoni F, Cuneo A, Pinto A, Trentin L, Bocchia M, Coviello E, MC, Morotti A, Falini B, Turrin M, Tafuri A, Billio A, Gentile M, Lemoli M, Venditti A, Della Porta M, Lanza F, Rigacci L, Tosi P, Mohamed S, Corso A, Luppi M, Giuliani N, Busca A, Pagano L, Bruno R, Grossi P, Corradini P, Passamonti F, Arcaini L., Zappasodi, P, Cattaneo, C, Ferretti, V, Mina, R, Ferreri, A, Merli, F, Oberti, M, Krampera, M, Romano, A, Zerbi, C, Ferrari, J, Cavo, M, Marco Salvini, M, Bertù, L, Fracchiolla, N, Marchesi, F, Massaia, M, Marasco, V, Cairoli, R, Scattolin, A, Vannucchi, A, Gambacorti-Passerini, C, Musto, P, Gherlinzoni, F, Cuneo, A, Pinto, A, Trentin, L, Bocchia, M, Galimberti, Coviello, E, Mc, Morotti, A, Falini, B, Turrin, M, Tafuri, A, Billio, A, Gentile, M, Lemoli, M, 37, Venditti, A, Della Porta, M, Lanza, F, Rigacci, L, Tosi, P, Mohamed, S, Corso, A, Luppi, M, Giuliani, N, Busca, A, Pagano, L, Bruno, R, Grossi, P, Corradini, P, Passamonti, F, Arcaini, L, Zappasodi P, Cattaneo C, Ferretti V, Mina R, Ferreri AJ, Merli F, Oberti M, Krampera M, Romano A, Zerbi C, Ferrari J, Cavo M, Marco Salvini M, Bertù L, Fracchiolla N, Marchesi F, Massaia M, Marasco V, Cairoli R, Scattolin AM, Vannucchi AM, Gambacorti-Passerini C, Musto P, Gherlinzoni F, Cuneo A, Pinto A, Trentin L, Bocchia M, Coviello E, MC, Morotti A, Falini B, Turrin M, Tafuri A, Billio A, Gentile M, Lemoli M, Venditti A, Della Porta M, Lanza F, Rigacci L, Tosi P, Mohamed S, Corso A, Luppi M, Giuliani N, Busca A, Pagano L, Bruno R, Grossi P, Corradini P, Passamonti F, and Arcaini L.

Abstract

The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5–36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis.

Published
2022

4. P07 BORTEZOMIB-MELPHALAN-PREDNISONE (VMP) VS. LENALIDOMIDE-DEXAMETHASONE (RD) IN REAL-LIFE MULTIPLE MYELOMA PATIENTS INELIGIBLE FOR TRANSPLANT: UPDATED ANALYSIS OF THE RANDOMIZED PHASE IV REAL MM TRIAL

Author

Larocca, A., primary, D’Agostino, M., additional, Giuliani, N., additional, Antonioli, E., additional, Zambello, R., additional, Ronconi, S., additional, Vincelli, I. D., additional, Ciceri, F., additional, Falcone, A. P., additional, Michieli, M., additional, Cattel, F., additional, Capra, A., additional, Grasso, M., additional, Cafro, A. M., additional, Bonello, F., additional, Floris, R., additional, Offidani, M., additional, Sciorsi, E., additional, Pietrantuono, G., additional, Curci, P., additional, Patriarca, F., additional, Cavo, M., additional, Mangiacavalli, S., additional, Benevolo, G., additional, Evangelista, A., additional, Ciccone, G., additional, Boccadoro, M., additional, Bruno, B., additional, and Bringhen, S., additional

Published
2023
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9. Secondary infections worsen the outcome of COVID-19 in patients with hematological malignancies: A report from the ITA-HEMA-COV

Author

Zappasodi P, Cattaneo C, Ferretti V, Mina R, Ferreri AJ, Merli F, Oberti M, Krampera M, Romano A, Zerbi C, Ferrari J, Cavo M, Marco Salvini M, Bertù L, Fracchiolla N, Marchesi F, Massaia M, Marasco V, Cairoli R, Scattolin AM, Vannucchi AM, Gambacorti-Passerini C, Musto P, Gherlinzoni F, Cuneo A, Pinto A, Trentin L, Bocchia M, Galimberti, Coviello E, Morotti A, Falini B, Turrin M, Tafuri A, Billio A, Gentile M, Lemoli M, Venditti A, Della Porta M, Lanza F, Rigacci L, Tosi P, Mohamed S, Corso A, Luppi M, Giuliani N, Busca A, Pagano L, Bruno R, Grossi P, Corradini P, Passamonti F, Arcaini L., Zappasodi, P, Cattaneo, C, Ferretti, V, Mina, R, Ferreri, A, Merli, F, Oberti, M, Krampera, M, Romano, A, Zerbi, C, Ferrari, J, Cavo, M, Marco Salvini, M, Bertù, L, Fracchiolla, N, Marchesi, F, Massaia, M, Marasco, V, Cairoli, R, Scattolin, A, Vannucchi, A, Gambacorti-Passerini, C, Musto, P, Gherlinzoni, F, Cuneo, A, Pinto, A, Trentin, L, Bocchia, M, Galimberti, Coviello, E, Mc, Morotti, A, Falini, B, Turrin, M, Tafuri, A, Billio, A, Gentile, M, Lemoli, M, Venditti, A, Della Porta, M, Lanza, F, Rigacci, L, Tosi, P, Mohamed, S, Corso, A, Luppi, M, Giuliani, N, Busca, A, Pagano, L, Bruno, R, Grossi, P, Corradini, P, Passamonti, F, Arcaini, L, Zappasodi, Patrizia, Cattaneo, Chiara, Ferretti, Virginia Valeria, Mina, Roberto, Ferreri, Andrés José María, Merli, Francesco, Oberti, Margherita, Krampera, Mauro, Romano, Alessandra, Zerbi, Caterina, Ferrari, Jacqueline, Cavo, Michele, Salvini, Marco, Bertù, Lorenza, Fracchiolla, Nicola Stefano, Marchesi, Francesco, Massaia, Massimo, Marasco, Vincenzo, Cairoli, Roberto, Scattolin, Anna Maria, Vannucchi, Alessandro Maria, Gambacorti-Passerini, Carlo, Musto, Pellegrino, Gherlinzoni, Filippo, Cuneo, Antonio, Pinto, Antonello, Trentin, Livio, Bocchia, Monica, Galimberti, Sara, Coviello, Elisa, Tisi, Maria Chiara, Morotti, Alessandro, Falini, Brunangelo, Turrini, Mauro, Tafuri, Agostino, Billio, Atto, Gentile, Massimo, Lemoli, Roberto Massimo, Venditti, Adriano, Della Porta, Matteo Giovanni, Lanza, Francesco, Rigacci, Luigi, Tosi, Patrizia, Mohamed, Sara, Corso, Alessandro, Luppi, Mario, Giuliani, Nicola, Busca, Alessandro, Pagano, Livio, Bruno, Raffaele, Grossi, Paolo Antonio, Corradini, Paolo, Passamonti, Francesco, and Arcaini, Luca

Subjects
Cancer Research, Lymphoma, Coinfection, COVID-19, Hematology, General Medicine, Settore MED/15, hematological malignancie, secondary infections, Settore MED/15 - MALATTIE DEL SANGUE, COVID-19 Testing, Oncology, Hematologic Neoplasms, secondary infection, outcome, Humans, hematological malignancies, Aged
Abstract

The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5-36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis.

Published
2022

11. P850: THE HUMORAL AND CELLULAR RESPONSE TO SARS-COV-2 MRNA VACCINATION IN PATIENTS WITH MULTIPLE MYELOMA AND PRE-MALIGNANT MONOCLONAL GAMMOPATHIES: IMPACT OF OMICRON VARIANT

Author

Storti, P., primary, Marchica, V., additional, Vescovini, R., additional, Franceschi, V., additional, Russo, L., additional, Raimondi, V., additional, Toscani, D., additional, Burroughs Garcia, J., additional, Iannozzi, N. T., additional, Dalla Palma, B., additional, Giaimo, M. T., additional, Notarfranchi, L., additional, Donofrio, G., additional, and Giuliani, N., additional

Published
2022
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12. PB1984: ELOTUZUMAB PLUS LENALIDOMIDE AND DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: EXTENDED 3-YEAR FOLLOW-UP OF AN ITALIAN, MULTICENTER, EXPERIENCE OUTSIDE OF CONTROLLED CLINICAL TRIALS

Author

Bruzzese, A., primary, Derudas, D., additional, Galli, M., additional, Martino, E. A., additional, Rocco, S., additional, Conticello, C., additional, Califano, C., additional, Giuliani, N., additional, Mangicavalli, S., additional, Farina, G., additional, Lombardo, A., additional, Brunori, M., additional, Rossi, E., additional, Antonioli, E., additional, Ria, R., additional, Zambello, R., additional, Di Renzo, N., additional, Mele, G., additional, Marcacci, G., additional, Pietrantuono, G., additional, Palumbo, G., additional, Cascavilla, N., additional, Cerchione, C., additional, Belotti, A., additional, Criscuolo, C., additional, Uccello, G., additional, Curci, P., additional, Vigna, E., additional, Mendicino, F., additional, Iaccino, E., additional, Mimmi, S., additional, Botta, C., additional, Vincelli, D., additional, Sgherza, N., additional, Bonalumi, A., additional, Cupelli, L., additional, Stocchi, R., additional, Martino, M., additional, Ballanti, S., additional, Gangemi, D., additional, Gagliardi, A., additional, Gamberi, B., additional, Pompa, A., additional, Tripepi, G., additional, Frigeri, F., additional, Consoli, U., additional, Bringhen, S., additional, Zamagni, E., additional, Patriarca, F., additional, De Stefano, V., additional, Di Raimondo, F., additional, Palmieri, S., additional, Petrucci, M. T., additional, Offidani, M., additional, Musto, P., additional, Boccadoro, M., additional, Cavo, M., additional, Neri, A., additional, Morabito, F., additional, and Gentile, M., additional

Published
2022
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13. Secondary infections worsen the outcome of COVID-19 in patients with hematological malignancies: A report from the ITA-HEMA-COV

Author

Zappasodi, P., Cattaneo, C., Valeria Ferretti, V., Mina, R., Jose Maria Ferreri, A., Merli, F., Oberti, M., Krampera, M., Romano, A., Zerbi, C., Ferrari, J., Cavo, M., Salvini, M., Bertu, L., Stefano Fracchiolla, N., Marchesi, F., Massaia, M., Marasco, V., Cairoli, R., Maria Scattolin, A., Maria Vannucchi, A., Gambacorti-Passerini, C., Musto, P., Gherlinzoni, F., Cuneo, A., Pinto, A., Trentin, L., Bocchia, M., Galimberti, S., Coviello, E., Chiara Tisi, M., Morotti, A., Falini, B., Turrini, M., Tafuri, A., Billio, A., Gentile, M., Massimo Lemoli, R., Venditti, A., Giovanni Della Porta, M., Lanza, F., Rigacci, L., Tosi, P., Mohamed, S., Corso, A., Luppi, M., Giuliani, N., Busca, A., Pagano, Livio, Bruno, R., Antonio Grossi, P., Corradini, P., Passamonti, F., Arcaini, L., Pagano L. (ORCID:0000-0001-8287-928X), Zappasodi, P., Cattaneo, C., Valeria Ferretti, V., Mina, R., Jose Maria Ferreri, A., Merli, F., Oberti, M., Krampera, M., Romano, A., Zerbi, C., Ferrari, J., Cavo, M., Salvini, M., Bertu, L., Stefano Fracchiolla, N., Marchesi, F., Massaia, M., Marasco, V., Cairoli, R., Maria Scattolin, A., Maria Vannucchi, A., Gambacorti-Passerini, C., Musto, P., Gherlinzoni, F., Cuneo, A., Pinto, A., Trentin, L., Bocchia, M., Galimberti, S., Coviello, E., Chiara Tisi, M., Morotti, A., Falini, B., Turrini, M., Tafuri, A., Billio, A., Gentile, M., Massimo Lemoli, R., Venditti, A., Giovanni Della Porta, M., Lanza, F., Rigacci, L., Tosi, P., Mohamed, S., Corso, A., Luppi, M., Giuliani, N., Busca, A., Pagano, Livio, Bruno, R., Antonio Grossi, P., Corradini, P., Passamonti, F., Arcaini, L., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5–36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis.

Published
2022

15. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

Author

Passamonti, F, Cattaneo, C, Arcaini, L, Bruna, R, Cavo, M, Merli, F, Angelucci, E, Krampera, M, Cairoli, R, Della Porta, M, Fracchiolla, N, Ladetto, M, Gambacorti Passerini, C, Salvini, M, Marchetti, M, Lemoli, R, Molteni, A, Busca, A, Cuneo, A, Romano, A, Giuliani, N, Galimberti, S, Corso, A, Morotti, A, Falini, B, Billio, A, Gherlinzoni, F, Visani, G, Tisi, M, Tafuri, A, Tosi, P, Lanza, F, Massaia, M, Turrini, M, Ferrara, F, Gurrieri, C, Vallisa, D, Martelli, M, Derenzini, E, Guarini, A, Conconi, A, Cuccaro, A, Cudillo, L, Russo, D, Ciambelli, F, Scattolin, A, Luppi, M, Selleri, C, Ortu La Barbera, E, Ferrandina, C, Di Renzo, N, Olivieri, A, Bocchia, M, Gentile, M, Marchesi, F, Musto, P, Federici, A, Candoni, A, Venditti, A, Fava, C, Pinto, A, Galieni, P, Rigacci, L, Armiento, D, Pane, F, Oberti, M, Zappasodi, P, Visco, C, Franchi, M, Grossi, P, Bertu, L, Corrao, G, Pagano, L, Corradini, P, Passamonti F., Cattaneo C., Arcaini L., Bruna R., Cavo M., Merli F., Angelucci E., Krampera M., Cairoli R., Della Porta M. G., Fracchiolla N., Ladetto M., Gambacorti Passerini C., Salvini M., Marchetti M., Lemoli R., Molteni A., Busca A., Cuneo A., Romano A., Giuliani N., Galimberti S., Corso A., Morotti A., Falini B., Billio A., Gherlinzoni F., Visani G., Tisi M. C., Tafuri A., Tosi P., Lanza F., Massaia M., Turrini M., Ferrara F., Gurrieri C., Vallisa D., Martelli M., Derenzini E., Guarini A., Conconi A., Cuccaro A., Cudillo L., Russo D., Ciambelli F., Scattolin A. M., Luppi M., Selleri C., Ortu La Barbera E., Ferrandina C., Di Renzo N., Olivieri A., Bocchia M., Gentile M., Marchesi F., Musto P., Federici A. B., Candoni A., Venditti A., Fava C., Pinto A., Galieni P., Rigacci L., Armiento D., Pane F., Oberti M., Zappasodi P., Visco C., Franchi M., Grossi P. A., Bertu L., Corrao G., Pagano L., Corradini P., Passamonti, F, Cattaneo, C, Arcaini, L, Bruna, R, Cavo, M, Merli, F, Angelucci, E, Krampera, M, Cairoli, R, Della Porta, M, Fracchiolla, N, Ladetto, M, Gambacorti Passerini, C, Salvini, M, Marchetti, M, Lemoli, R, Molteni, A, Busca, A, Cuneo, A, Romano, A, Giuliani, N, Galimberti, S, Corso, A, Morotti, A, Falini, B, Billio, A, Gherlinzoni, F, Visani, G, Tisi, M, Tafuri, A, Tosi, P, Lanza, F, Massaia, M, Turrini, M, Ferrara, F, Gurrieri, C, Vallisa, D, Martelli, M, Derenzini, E, Guarini, A, Conconi, A, Cuccaro, A, Cudillo, L, Russo, D, Ciambelli, F, Scattolin, A, Luppi, M, Selleri, C, Ortu La Barbera, E, Ferrandina, C, Di Renzo, N, Olivieri, A, Bocchia, M, Gentile, M, Marchesi, F, Musto, P, Federici, A, Candoni, A, Venditti, A, Fava, C, Pinto, A, Galieni, P, Rigacci, L, Armiento, D, Pane, F, Oberti, M, Zappasodi, P, Visco, C, Franchi, M, Grossi, P, Bertu, L, Corrao, G, Pagano, L, Corradini, P, Passamonti F., Cattaneo C., Arcaini L., Bruna R., Cavo M., Merli F., Angelucci E., Krampera M., Cairoli R., Della Porta M. G., Fracchiolla N., Ladetto M., Gambacorti Passerini C., Salvini M., Marchetti M., Lemoli R., Molteni A., Busca A., Cuneo A., Romano A., Giuliani N., Galimberti S., Corso A., Morotti A., Falini B., Billio A., Gherlinzoni F., Visani G., Tisi M. C., Tafuri A., Tosi P., Lanza F., Massaia M., Turrini M., Ferrara F., Gurrieri C., Vallisa D., Martelli M., Derenzini E., Guarini A., Conconi A., Cuccaro A., Cudillo L., Russo D., Ciambelli F., Scattolin A. M., Luppi M., Selleri C., Ortu La Barbera E., Ferrandina C., Di Renzo N., Olivieri A., Bocchia M., Gentile M., Marchesi F., Musto P., Federici A. B., Candoni A., Venditti A., Fava C., Pinto A., Galieni P., Rigacci L., Armiento D., Pane F., Oberti M., Zappasodi P., Visco C., Franchi M., Grossi P. A., Bertu L., Corrao G., Pagano L., and Corradini P.

Abstract

Background: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19. Methods: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing. Findings: We enrolled 536 patients with a median follow-up of 20 days (IQR 10–34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77–2·34) in our whole study cohort and 3·72 (2·86–4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1–44·9). Older age (hazard ratio 1·03, 95% CI 1·01–1·05); progressive disease status (2·10, 1·41–3·12); diagnosis of

Published
2020

23. [18F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma

Author

Valtorta, S, Toscani, D, Chiu, M, Sartori, A, Coliva, A, Brevi, A, Taurino, G, Grioni, M, Ruffini, L, Vacondio, F, Zanardi, F, Bellone, M, Moresco, R, Bussolati, O, Giuliani, N, Valtorta, Silvia, Toscani, Denise, Chiu, Martina, Sartori, Andrea, Coliva, Angela, Brevi, Arianna, Taurino, Giuseppe, Grioni, Matteo, Ruffini, Livia, Vacondio, Federica, Zanardi, Franca, Bellone, Matteo, Moresco, Rosa Maria, Bussolati, Ovidio, Giuliani, Nicola, Valtorta, S, Toscani, D, Chiu, M, Sartori, A, Coliva, A, Brevi, A, Taurino, G, Grioni, M, Ruffini, L, Vacondio, F, Zanardi, F, Bellone, M, Moresco, R, Bussolati, O, Giuliani, N, Valtorta, Silvia, Toscani, Denise, Chiu, Martina, Sartori, Andrea, Coliva, Angela, Brevi, Arianna, Taurino, Giuseppe, Grioni, Matteo, Ruffini, Livia, Vacondio, Federica, Zanardi, Franca, Bellone, Matteo, Moresco, Rosa Maria, Bussolati, Ovidio, and Giuliani, Nicola

Abstract

The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [18F]FDG-PET has some limitations and there is a portion of MM patients who are negative. Glutamine (Gln) addiction has been recently described as a typical metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed so far and is investigated in this study in preclinical models. Firstly, we have synthesized enantiopure (2S,4R)-4-fluoroglutamine (4-FGln) and validated it as a Gln transport analogue in human MM cell lines, comparing its uptake with that of 3H-labelled Gln. We then radiosynthesized [18F]4-FGln, tested its uptake in two different in vivo murine MM models, and checked the effect of Bortezomib, a proteasome inhibitor currently used in the treatment of MM. Both [18F]4-FGln and [18F]FDG clearly identified the spleen as site of MM cell colonization in C57BL/6 mice, challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice, subcutaneously injected with human MM JJN3 cells, showed high values of both [18F]4-FGln and [18F]FDG uptake. Bortezomib significantly reduced the uptake of both radiopharmaceuticals in comparison with vehicle at post treatment PET. However, a reduction of glutaminolytic, but not of glycolytic, tumor volume was evident in mice showing the highest response to Bortezomib. Our data indicate that [18F](2S,4R)-4-FGln is a new PET tracer in preclinical MM models, yielding a rationale to design studies in MM patients.

Published
2021

36. Bortezomib-dexamethasone as maintenance therapy or early retreatment at biochemical relapse versus observation in relapsed/refractory multiple myeloma patients: a randomized phase II study

Author

Mina, R. (Roberto), Belotti, A. (Angelo), Petrucci, M. (Maria), Zambello, R. (Renato), Capra, A. (Andrea), Di Lullo, G. (Giacomo), Ronconi, S. (Sonia), Pescosta, N. (Norbert), Grasso, M. (Mariella), Monaco, F. (Federico), Cellini, C. (Claudia), Gobbi, M. (Marco), Ballanti, S. (Stelvio), de Fabritiis, P. (Paolo), Mosca-Siez, M.L. (Maria Letizia), Marchetti, M. (Monia), Liberati, A.M., Offidani, M. (Massimo), Giuliani, N. (Nicola), Ria, R. (Roberto), Musto, P. (Pellegrino), Romano, A. (Alessandra), Sonneveld, P. (Pieter), Boccadoro, M. (Mario), Larocca, A. (Alessandra), Mina, R. (Roberto), Belotti, A. (Angelo), Petrucci, M. (Maria), Zambello, R. (Renato), Capra, A. (Andrea), Di Lullo, G. (Giacomo), Ronconi, S. (Sonia), Pescosta, N. (Norbert), Grasso, M. (Mariella), Monaco, F. (Federico), Cellini, C. (Claudia), Gobbi, M. (Marco), Ballanti, S. (Stelvio), de Fabritiis, P. (Paolo), Mosca-Siez, M.L. (Maria Letizia), Marchetti, M. (Monia), Liberati, A.M., Offidani, M. (Massimo), Giuliani, N. (Nicola), Ria, R. (Roberto), Musto, P. (Pellegrino), Romano, A. (Alessandra), Sonneveld, P. (Pieter), Boccadoro, M. (Mario), and Larocca, A. (Alessandra)

Published
2020
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37. Bortezomib-dexamethasone as maintenance therapy or early retreatment at biochemical relapse versus observation in relapsed/refractory multiple myeloma patients: a randomized phase II study

Author

Mina, R, Belotti, A, Petrucci, MT, Zambello, R, Capra, A, Di Lullo, G, Ronconi, S, Pescosta, N, Grasso, M, Monaco, F, Cellini, C, Gobbi, M, Ballanti, S, de Fabritiis, P, Mosca-Siez, ML, Marchetti, M, Liberati, AM, Offidani, M, Giuliani, N, Ria, R, Musto, P, Romano, A, Sonneveld, Pieter, Boccadoro, M, Larocca, A, Mina, R, Belotti, A, Petrucci, MT, Zambello, R, Capra, A, Di Lullo, G, Ronconi, S, Pescosta, N, Grasso, M, Monaco, F, Cellini, C, Gobbi, M, Ballanti, S, de Fabritiis, P, Mosca-Siez, ML, Marchetti, M, Liberati, AM, Offidani, M, Giuliani, N, Ria, R, Musto, P, Romano, A, Sonneveld, Pieter, Boccadoro, M, and Larocca, A

Published
2020

39. [18f]-(2S,4R)-4-Fluoroglutamine As a New Positron Emission Tomography Tracer in Multiple Myeloma

Author

Giuliani, N, Valtorta, S, Chiu, M, Toscani, D, Sartori, A, Coliva, A, Brevi, A, Battaglia, S, Vicario, E, Taurino, G, Grioni, M, Ferlenghi, F, Ruffini, L, Vacondio, F, Zanardi, F, Bellone, M, Moresco, R, Bussolati, O, Giuliani, Nicola, Valtorta, Silvia, Chiu, Martina, Toscani, Denise, Sartori, Andrea, Coliva, Angela, Brevi, Arianna, Battaglia, Stefania, Vicario, Emanuela, Taurino, Giuseppe, Grioni, Matteo, Ferlenghi, Francesca, Ruffini, Livia, Vacondio, Federica, Zanardi, Franca, Bellone, Matteo, Moresco, Rosa Maria, Bussolati, Ovidio, Giuliani, N, Valtorta, S, Chiu, M, Toscani, D, Sartori, A, Coliva, A, Brevi, A, Battaglia, S, Vicario, E, Taurino, G, Grioni, M, Ferlenghi, F, Ruffini, L, Vacondio, F, Zanardi, F, Bellone, M, Moresco, R, Bussolati, O, Giuliani, Nicola, Valtorta, Silvia, Chiu, Martina, Toscani, Denise, Sartori, Andrea, Coliva, Angela, Brevi, Arianna, Battaglia, Stefania, Vicario, Emanuela, Taurino, Giuseppe, Grioni, Matteo, Ferlenghi, Francesca, Ruffini, Livia, Vacondio, Federica, Zanardi, Franca, Bellone, Matteo, Moresco, Rosa Maria, and Bussolati, Ovidio

Published
2019

40. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study

Author

Mohty, M. Terpos, E. Mateos, M.-V. Cavo, M. Lejniece, S. Beksac, M. Bekadja, M.A. Legiec, W. Dimopoulos, M. Stankovic, S. Durán, M.S. De Stefano, V. Corso, A. Kochkareva, Y. Laane, E. Berthou, C. Salwender, H. Masliak, Z. Pečeliūnas, V. Willenbacher, W. Silva, J. Louw, V. Nemet, D. Borbényi, Z. Abadi, U. Pedersen, R.S. Černelč, P. Potamianou, A. Couturier, C. Feys, C. Thoret-Bauchet, F. Boccadoro, M. Bekadja, M. Hamladji, R.-M. Ali, H.A. Hamdi, S. Touhami, H. Mansour, N.S. Linkesch, W. Abildgaard, N. Hein, M. Eveillard, J.R. Yamani, A.E. Moreau, P. Sanhes, L. Lepeu, G. Laribi, K. Jourdan, E. Fitoussi, O. Allangba, O. Fleury, J. Escoffre, M. Benramdane, R. Cartron, G. Dine, G. Legouffe, E. Harich, H.-D. Illmer, T. Dörfel, S. Hannig, C.V. Koenigsmann, M. Prange-Krex, G. Tamm, I. Zeller, W. Maasberg, M. Schlag, R. Klausmann, M. Uhlig, J. Alkemper, B. Schütz, S. Tessen, H.-W. Mohr, B. Schmidt, P. Heinrich, B. Hebart, H. Seipelt, G. Zoeller, T. Heits, F. Müller-Naendrup, C. Hansen, R. Repp, R. Von Weikersthal, L.F. Schmits, R. Heßling, J. Krammer-Steiner, B. Janzen, V. Schauer, M. Grüner, M.W. Kisro, J. Denzlinger, C. Freier, W. Junghanss, C. Görner, M. Laichinger, K. Ostermann, H. Dürk, H. Hess, G. Reich, G. Matsouka, P. Pouli, A. Anagnostopoulos, A. Masszi, T. Ivanyi, J. Szomor, A. Nagler, A. Magen, H. Avivi, I. Quitt, M. Palumbo, A. Za, T. Vallisa, D. Foa, R. Bosi, A. Vacca, A. Lanza, F. Palazzo, G. Avvisati, G. Ferrara, F. Consoli, U. Cantonetti, M. Angelucci, E. Califano, C. Di Raimondo, F. Guarini, A. Musso, M. Pizzuti, M. Giuliani, N. Ardizzoia, A. Di Renzo, N. Gaidano, G. Gozzetti, A. Pitini, V. Farina, G. Centurioni, R. De Fabritiis, P. Iuliano, F. La Nasa, G. La Verde, G. Pane, F. Recine, U. La Targia, M. Mineo, G. Cangialosi, C. Fagnani, D. Federici, A. Romano, A. Specchia, G. Storti, S. Bongarzoni, V. Bacigalupo, A. Gobbi, M. Latte, G. Mannina, D. Capalbo, S. Jurgutis, M. Woszczyk, D. Hołojda, J. Gornik, S. Pluta, A. Morawiec-Szymonik, E. Kyrcz-Krzemien, S. Homenda, W. Grosicki, S. Sulek, K. Lange, A. Kloczko, J. Starzak-Gwozdz, J. Hellmann, A. Komarnicki, M. Kuliczkowski, K. Viveiros, C. Gonçalves, C. Esefyeva, N. Kaplanov, K. Volodicheva, E. Laricheva, E. Dergacheva, V. Chukavina, M. Volchenko, N. Nazarova, I. Anchukova, L. Ovanesova, E. Salogub, G. Magomedova, L. Kuznetsova, I. Osyunikhina, S. Serdyuk, O. Karyagina, E. Ivanova, V. Černelč, S.P. Coetzee, C. Gunther, K. Moodley, D. Duran, S. Gutiérrez, A.E. De Oteyza, J.P. Capote, F.J. Casanova, M. Sanchez, J.M. Rios-Herranz, E. Ibañez-Garcia, J. Herranz, M.J. Hernandez, B. Sanchez, S.S. Escalante, F. Carnicero, F. Lleonart, J.B. Gironella, M. Martínez, R. De La Guia, A.L. Palomera, L. Iglesias, R. Ramos, F.S. De La Serna, J. Sanchez, P.G. Vidal, J.B. Morfa, M.D. Beksac, T.-M. Vural, F. Aydin, Y. Unal, A. Goker, H. Bilgir, O. Guvenc, B. Turgut, M. Ozet, G.G. Ali, R. Kyselyova, M. Glushko, N. Vybyrana, R. Skrypnyk, I. Tretyak, N. Kharchevska, T. Dyagil, I. Popovs'ka, T. Shimanskiy, V. Lysa, T. Oliynyk, H. Vilchevskaya, K. Kryachok, I. Popovych, Y. Romanyuk, N. Yushchenko, N. Kaplan, P. Rekhtman, G. Pylypenko, H. Kozlov, V. Drach, J. Harousseau, J.-L. Einsele, H. Goldschmidt, H. Facon, T. Michalet, M. Savchenko, V.G. De la Rubia, J. Cook, G. Mellqvist, U.-H. Ludwig, H. EMMOS Investigators

Abstract

Multiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits. © 2018 The Authors

Published
2018

42. Microvesicles released from multiple myeloma cells are equipped with ectoenzymes belonging to canonical and non-canonical adenosinergic pathways and produce adenosine from ATP and NAD+

Author

Morandi, F., primary, Marimpietri, D., additional, Horenstein, A. L., additional, Bolzoni, M., additional, Toscani, D., additional, Costa, F., additional, Castella, B., additional, Faini, A. C., additional, Massaia, M., additional, Pistoia, V., additional, Giuliani, N., additional, and Malavasi, F., additional

Published
2018
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43. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study

Author

Mohty, M., Terpos, E., Mateos, M. -V., Cavo, M., Lejniece, S., Beksac, M., Bekadja, M. A., Legiec, W., Dimopoulos, M., Stankovic, S., Duran, M. S., De Stefano, Valerio, Corso, A., Kochkareva, Y., Laane, E., Berthou, C., Salwender, H., Masliak, Z., Peceliunas, V., Willenbacher, W., Silva, J., Louw, V., Nemet, D., Borbenyi, Z., Abadi, U., Pedersen, R. S., Cernelc, P., Potamianou, A., Couturier, C., Feys, C., Thoret-Bauchet, F., Boccadoro, M., Bekadja, M., Hamladji, R. -M., Ali, H. A., Hamdi, S., Touhami, H., Mansour, N. S., Linkesch, W., Abildgaard, N., Hein, M., Eveillard, J. R., Yamani, A. E., Moreau, P., Sanhes, L., Lepeu, G., Laribi, K., Jourdan, E., Fitoussi, O., Allangba, O., Fleury, J., Escoffre, M., Benramdane, R., Cartron, G., Dine, G., Legouffe, E., Harich, H. -D., Illmer, T., Dorfel, S., Hannig, C. V., Koenigsmann, M., Prange-Krex, G., Tamm, I., Zeller, W., Maasberg, M., Schlag, R., Klausmann, M., Uhlig, J., Alkemper, B., Schutz, S., Tessen, H. -W., Mohr, B., Schmidt, P., Heinrich, B., Hebart, H., Seipelt, G., Zoeller, T., Heits, F., Muller-Naendrup, C., Hansen, R., Repp, R., Von Weikersthal, L. F., Schmits, R., Hessling, J., Krammer-Steiner, B., Janzen, V., Schauer, M., Gruner, M. W., Kisro, J., Denzlinger, C., Freier, W., Junghanss, C., Gorner, M., Laichinger, K., Ostermann, H., Durk, H., Hess, G., Reich, G., Matsouka, P., Pouli, A., Anagnostopoulos, A., Masszi, T., Ivanyi, J., Szomor, A., Nagler, A., Magen, H., Avivi, I., Quitt, M., Palumbo, A., Za, Tommaso, Vallisa, D., Foa, R., Bosi, A., Vacca, A., Lanza, F., Palazzo, G., Avvisati, G., Ferrara, F., Consoli, U., Cantonetti, M., Angelucci, E., Califano, C., Di Raimondo, F., Guarini, A., Musso, M., Pizzuti, M., Giuliani, N., Ardizzoia, A., Di Renzo, N., Gaidano, G., Gozzetti, A., Pitini, V., Farina, G., Centurioni, R., De Fabritiis, P., Iuliano, F., La Nasa, G., La Verde, G., Pane, F., Recine, U., La Targia, M., Mineo, G., Cangialosi, C., Fagnani, D., Federici, A., Romano, A., Specchia, G., Storti, Sergio, Bongarzoni, V., Bacigalupo, Andrea, Gobbi, M., Latte, G., Mannina, D., Capalbo, S., Jurgutis, M., Woszczyk, D., Holojda, J., Gornik, S., Pluta, A., Morawiec-Szymonik, E., Kyrcz-Krzemien, S., Homenda, W., Grosicki, S., Sulek, K., Lange, A., Kloczko, J., Starzak-Gwozdz, J., Hellmann, A., Komarnicki, M., Kuliczkowski, K., Viveiros, C., Goncalves, C., Esefyeva, N., Kaplanov, K., Volodicheva, E., Laricheva, E., Dergacheva, V., Chukavina, M., Volchenko, N., Nazarova, I., Anchukova, L., Ovanesova, E., Salogub, G., Magomedova, L., Kuznetsova, I., Osyunikhina, S., Serdyuk, O., Karyagina, E., Ivanova, V., Cernelc, S. P., Coetzee, C., Gunther, K., Moodley, D., Duran, S., Gutierrez, A. E., De Oteyza, J. P., Capote, F. J., Casanova, M., Sanchez, J. M., Rios-Herranz, E., Ibanez-Garcia, J., Herranz, M. J., Hernandez, B., Sanchez, S. S., Escalante, F., Carnicero, F., Lleonart, J. B., Gironella, M., Martinez, R., De La Guia, A. L., Palomera, L., Iglesias, R., Ramos, F. S., De La Serna, J., Sanchez, P. G., Vidal, J. B., Morfa, M. D., Beksac, T. -M., Vural, F., Aydin, Y., Unal, A., Goker, H., Bilgir, O., Guvenc, B., Turgut, M., Ozet, G. G., Ali, R., Kyselyova, M., Glushko, N., Vybyrana, R., Skrypnyk, I., Tretyak, N., Kharchevska, T., Dyagil, I., Popovs'Ka, T., Shimanskiy, V., Lysa, T., Oliynyk, H., Vilchevskaya, K., Kryachok, I., Popovych, Y., Romanyuk, N., Yushchenko, N., Kaplan, P., Rekhtman, G., Pylypenko, H., Kozlov, V., Drach, J., Harousseau, J. -L., Einsele, H., Goldschmidt, H., Facon, T., Michalet, M., Savchenko, V. G., De la Rubia, J., Cook, G., Mellqvist, U. -H., Ludwig, H., De Stefano V. (ORCID:0000-0002-5178-5827), Za T., Storti S. (ORCID:0000-0002-4374-3985), Bacigalupo A. (ORCID:0000-0002-9119-567X), Mohty, M., Terpos, E., Mateos, M. -V., Cavo, M., Lejniece, S., Beksac, M., Bekadja, M. A., Legiec, W., Dimopoulos, M., Stankovic, S., Duran, M. S., De Stefano, Valerio, Corso, A., Kochkareva, Y., Laane, E., Berthou, C., Salwender, H., Masliak, Z., Peceliunas, V., Willenbacher, W., Silva, J., Louw, V., Nemet, D., Borbenyi, Z., Abadi, U., Pedersen, R. S., Cernelc, P., Potamianou, A., Couturier, C., Feys, C., Thoret-Bauchet, F., Boccadoro, M., Bekadja, M., Hamladji, R. -M., Ali, H. A., Hamdi, S., Touhami, H., Mansour, N. S., Linkesch, W., Abildgaard, N., Hein, M., Eveillard, J. R., Yamani, A. E., Moreau, P., Sanhes, L., Lepeu, G., Laribi, K., Jourdan, E., Fitoussi, O., Allangba, O., Fleury, J., Escoffre, M., Benramdane, R., Cartron, G., Dine, G., Legouffe, E., Harich, H. -D., Illmer, T., Dorfel, S., Hannig, C. V., Koenigsmann, M., Prange-Krex, G., Tamm, I., Zeller, W., Maasberg, M., Schlag, R., Klausmann, M., Uhlig, J., Alkemper, B., Schutz, S., Tessen, H. -W., Mohr, B., Schmidt, P., Heinrich, B., Hebart, H., Seipelt, G., Zoeller, T., Heits, F., Muller-Naendrup, C., Hansen, R., Repp, R., Von Weikersthal, L. F., Schmits, R., Hessling, J., Krammer-Steiner, B., Janzen, V., Schauer, M., Gruner, M. W., Kisro, J., Denzlinger, C., Freier, W., Junghanss, C., Gorner, M., Laichinger, K., Ostermann, H., Durk, H., Hess, G., Reich, G., Matsouka, P., Pouli, A., Anagnostopoulos, A., Masszi, T., Ivanyi, J., Szomor, A., Nagler, A., Magen, H., Avivi, I., Quitt, M., Palumbo, A., Za, Tommaso, Vallisa, D., Foa, R., Bosi, A., Vacca, A., Lanza, F., Palazzo, G., Avvisati, G., Ferrara, F., Consoli, U., Cantonetti, M., Angelucci, E., Califano, C., Di Raimondo, F., Guarini, A., Musso, M., Pizzuti, M., Giuliani, N., Ardizzoia, A., Di Renzo, N., Gaidano, G., Gozzetti, A., Pitini, V., Farina, G., Centurioni, R., De Fabritiis, P., Iuliano, F., La Nasa, G., La Verde, G., Pane, F., Recine, U., La Targia, M., Mineo, G., Cangialosi, C., Fagnani, D., Federici, A., Romano, A., Specchia, G., Storti, Sergio, Bongarzoni, V., Bacigalupo, Andrea, Gobbi, M., Latte, G., Mannina, D., Capalbo, S., Jurgutis, M., Woszczyk, D., Holojda, J., Gornik, S., Pluta, A., Morawiec-Szymonik, E., Kyrcz-Krzemien, S., Homenda, W., Grosicki, S., Sulek, K., Lange, A., Kloczko, J., Starzak-Gwozdz, J., Hellmann, A., Komarnicki, M., Kuliczkowski, K., Viveiros, C., Goncalves, C., Esefyeva, N., Kaplanov, K., Volodicheva, E., Laricheva, E., Dergacheva, V., Chukavina, M., Volchenko, N., Nazarova, I., Anchukova, L., Ovanesova, E., Salogub, G., Magomedova, L., Kuznetsova, I., Osyunikhina, S., Serdyuk, O., Karyagina, E., Ivanova, V., Cernelc, S. P., Coetzee, C., Gunther, K., Moodley, D., Duran, S., Gutierrez, A. E., De Oteyza, J. P., Capote, F. J., Casanova, M., Sanchez, J. M., Rios-Herranz, E., Ibanez-Garcia, J., Herranz, M. J., Hernandez, B., Sanchez, S. S., Escalante, F., Carnicero, F., Lleonart, J. B., Gironella, M., Martinez, R., De La Guia, A. L., Palomera, L., Iglesias, R., Ramos, F. S., De La Serna, J., Sanchez, P. G., Vidal, J. B., Morfa, M. D., Beksac, T. -M., Vural, F., Aydin, Y., Unal, A., Goker, H., Bilgir, O., Guvenc, B., Turgut, M., Ozet, G. G., Ali, R., Kyselyova, M., Glushko, N., Vybyrana, R., Skrypnyk, I., Tretyak, N., Kharchevska, T., Dyagil, I., Popovs'Ka, T., Shimanskiy, V., Lysa, T., Oliynyk, H., Vilchevskaya, K., Kryachok, I., Popovych, Y., Romanyuk, N., Yushchenko, N., Kaplan, P., Rekhtman, G., Pylypenko, H., Kozlov, V., Drach, J., Harousseau, J. -L., Einsele, H., Goldschmidt, H., Facon, T., Michalet, M., Savchenko, V. G., De la Rubia, J., Cook, G., Mellqvist, U. -H., Ludwig, H., De Stefano V. (ORCID:0000-0002-5178-5827), Za T., Storti S. (ORCID:0000-0002-4374-3985), and Bacigalupo A. (ORCID:0000-0002-9119-567X)

Abstract

Multiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and

Published
2018

46. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma

Author

Cavo, M, Pantani, L, Petrucci, M, Patriarca, F, Zamagni, E, Donnarumma, D, Crippa, C, Boccadoro, M, Perrone, G, Falcone, A, Nozzoli, C, Zambello, R, Masini, L, Furlan, A, Brioli, A, Derudas, D, Ballanti, S, Dessanti, M, De Stefano, V, Carella, A, Marcatti, M, Nozza, A, Ferrara, F, Callea, V, Califano, C, Pezzi, A, Baraldi, A, Grasso, M, Musto, P, Palumbo, A, Tosi, P, Motta, M, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, F, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, M, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, A, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, M, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, Quartarone, E, Tosi P, Motta MR, Rizzi S, Fanin R, Buttignol S, Foà R, Levi A, Calabrese E, Rambaldi A, Galli M, Rossi G, Ferrari S, Bringhen S, Leoni P, Offidani M, Polloni C, Corradini P, Montefusco V, Torelli G, Narni F, Fioritoni G, Spadano A, Cortelazzo S, Pescosta N, Billio A, Lambertenghi Deliliers G, Baldini L, Onida F, Annaloro C, La Nasa G, Ledda A, Zaccaria A, Cellini C, De Fabritiis P, Caravita T, Siniscalchi A, Cascavilla N, Bosi A, Semenzato G, Gugliotta L, Merli F, Gherlinzoni F, Angelucci E, Martelli M, Petti MC, Pisani F, Leone G, Rossi E, Za T, Fianchi L, Catania G, Spriano M, Ciceri F, Peccatori J, Girlanda S, Santoro A, Castagna L, Palmieri S, Nobile F, D'Arco AM, Levis A, Primon V, Tamiazzo S, Guardigni L, Pasini S, Gallamini A, Pietrantuono G, Martorelli MC, Fattori P, Pasquini E, Galieni P, Ruggieri M, Morandi S, Tajana M, Amadori D, Ronconi S, Cangini D, Ceccolini M, Gobbi M, Ballerini F, Pane F, Catalano L, Cangialosi C, Vallisa D, Lazzaro A, Paladini G, De Sabbata G, Mozzana R, Ciambelli F, Pinotti G, Rodeghiero F, Elice F, Cantore N, Volpe S, Pavone V, Mele A, POGLIANI, ENRICO MARIA, Rossini F, Liberati A, Majolino I, De Rosa L, Amadori S, Rizzo M, Lauria F, Gozzetti A, Aglietta M, Capaldi A, Quarta G, Mele G, Storti S, Fraticelli V, Morabito F, Gentile C, Capalbo S, Gianni A, Magni M, Mettivier V, Nunziata G, Rizzoli V, Giuliani N, Crugnola M, Bernasconi C, Fregoni V, Visani G, Olivieri A, Pizzuti M, La Verde G, Moscetti A, Avvisati G, Tirindelli M, Longinotti M, Podda L, Gallo E, Pregno P, Dammacco F, Perosa F, Russo D, Roccaro A, Bacigalupo A, Dominietto A, Musolino C, Quartarone E., Cavo, M, Pantani, L, Petrucci, M, Patriarca, F, Zamagni, E, Donnarumma, D, Crippa, C, Boccadoro, M, Perrone, G, Falcone, A, Nozzoli, C, Zambello, R, Masini, L, Furlan, A, Brioli, A, Derudas, D, Ballanti, S, Dessanti, M, De Stefano, V, Carella, A, Marcatti, M, Nozza, A, Ferrara, F, Callea, V, Califano, C, Pezzi, A, Baraldi, A, Grasso, M, Musto, P, Palumbo, A, Tosi, P, Motta, M, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, F, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, M, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, A, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, M, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, Quartarone, E, Tosi P, Motta MR, Rizzi S, Fanin R, Buttignol S, Foà R, Levi A, Calabrese E, Rambaldi A, Galli M, Rossi G, Ferrari S, Bringhen S, Leoni P, Offidani M, Polloni C, Corradini P, Montefusco V, Torelli G, Narni F, Fioritoni G, Spadano A, Cortelazzo S, Pescosta N, Billio A, Lambertenghi Deliliers G, Baldini L, Onida F, Annaloro C, La Nasa G, Ledda A, Zaccaria A, Cellini C, De Fabritiis P, Caravita T, Siniscalchi A, Cascavilla N, Bosi A, Semenzato G, Gugliotta L, Merli F, Gherlinzoni F, Angelucci E, Martelli M, Petti MC, Pisani F, Leone G, Rossi E, Za T, Fianchi L, Catania G, Spriano M, Ciceri F, Peccatori J, Girlanda S, Santoro A, Castagna L, Palmieri S, Nobile F, D'Arco AM, Levis A, Primon V, Tamiazzo S, Guardigni L, Pasini S, Gallamini A, Pietrantuono G, Martorelli MC, Fattori P, Pasquini E, Galieni P, Ruggieri M, Morandi S, Tajana M, Amadori D, Ronconi S, Cangini D, Ceccolini M, Gobbi M, Ballerini F, Pane F, Catalano L, Cangialosi C, Vallisa D, Lazzaro A, Paladini G, De Sabbata G, Mozzana R, Ciambelli F, Pinotti G, Rodeghiero F, Elice F, Cantore N, Volpe S, Pavone V, Mele A, POGLIANI, ENRICO MARIA, Rossini F, Liberati A, Majolino I, De Rosa L, Amadori S, Rizzo M, Lauria F, Gozzetti A, Aglietta M, Capaldi A, Quarta G, Mele G, Storti S, Fraticelli V, Morabito F, Gentile C, Capalbo S, Gianni A, Magni M, Mettivier V, Nunziata G, Rizzoli V, Giuliani N, Crugnola M, Bernasconi C, Fregoni V, Visani G, Olivieri A, Pizzuti M, La Verde G, Moscetti A, Avvisati G, Tirindelli M, Longinotti M, Podda L, Gallo E, Pregno P, Dammacco F, Perosa F, Russo D, Roccaro A, Bacigalupo A, Dominietto A, Musolino C, and Quartarone E.

Abstract

In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.

Published
2012

47. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma

Author

Cavo, Michele, Pantani, Lucia, Petrucci, Maria Teresa, Patriarca, Francesca, Zamagni, Elena, Donnarumma, Daniela, Crippa, Claudia, Boccadoro, Mario, Perrone, Giulia, Falcone, Antonietta, Nozzoli, Chiara, Zambello, Renato, Masini, Luciano, Furlan, Anna, Brioli, Annamaria, Derudas, Daniele, Ballanti, Stelvio, Dessanti, Maria Laura, De Stefano, Valerio, Carella, Angelo Michele, Marcatti, Magda, Nozza, Andrea, Ferrara, Felicetto, Callea, Vincenzo, Califano, Catello, Pezzi, Annalisa, Baraldi, Anna, Grasso, Mariella, Musto, Pellegrino, Palumbo, Antonio COLLABORATORI: Tosi, P, Motta, Mr, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, Franco, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, Mc, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, Am, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, Mc, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, Quartarone, E., Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A., Cavo, Michele, Pantani, Lucia, Petrucci, Maria Teresa, Patriarca, Francesca, Zamagni, Elena, Donnarumma, Daniela, Crippa, Claudia, Boccadoro, Mario, Perrone, Giulia, Falcone, Antonietta, Nozzoli, Chiara, Zambello, Renato, Masini, Luciano, Furlan, Anna, Brioli, Annamaria, Derudas, Daniele, Ballanti, Stelvio, Dessanti, Maria Laura, De Stefano, Valerio, Carella, Angelo Michele, Marcatti, Magda, Nozza, Andrea, Ferrara, Felicetto, Callea, Vincenzo, Califano, Catello, Pezzi, Annalisa, Baraldi, Anna, Grasso, Mariella, Musto, Pellegrino, Palumbo, Antonio, Cavo, M, Pantani, L, Petrucci, M, Patriarca, F, Zamagni, E, Donnarumma, D, Crippa, C, Boccadoro, M, Perrone, G, Falcone, A, Nozzoli, C, Zambello, R, Masini, L, Furlan, A, Brioli, A, Derudas, D, Ballanti, S, Dessanti, M, De Stefano, V, Carella, A, Marcatti, M, Nozza, A, Ferrara, F, Callea, V, Califano, C, Pezzi, A, Baraldi, A, Grasso, M, Musto, P, Palumbo, A, Tosi, P, Motta, M, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, F, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, M, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, A, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, M, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, and Quartarone, E

Subjects
Male, Boronic Acid, medicine.medical_treatment, PLUS DEXAMETHASONE, Phases of clinical research, Kaplan-Meier Estimate, Hematopoietic stem cell transplantation, Biochemistry, Antineoplastic Agent, Bortezomib-thalidomide-dexamethasone, Bortezomib, Immunosuppressive Agent, Autologous stem-cell transplantation, MULTIPLE MYELOMA, Antineoplastic Combined Chemotherapy Protocols, thalidomide-dexamethasone, Multiple myeloma, RANDOMIZED PHASE-3, LENALIDOMIDE, STEM CELL TRANSPLANTATION, Hematopoietic Stem Cell Transplantation, PHASE-III TRIAL, Hematology, Middle Aged, CHEMOTHERAPY, Prognosis, Boronic Acids, Combined Modality Therapy, Thalidomide, Transplantation, Autologou, Pyrazines, HIGH-DOSE MELPHALAN, INDUCTION TREATMENT, Female, Autologous, Immunosuppressive Agents, Pyrazine, Human, medicine.drug, MAINTENANCE THERAPY, medicine.medical_specialty, DOXORUBICIN, Antineoplastic Agents, Hormonal, Prognosi, Immunology, Urology, Antineoplastic Agents, dexamethasone, Transplantation, Autologous, Disease-Free Survival, Dexamethasone, Humans, Multiple Myeloma, Cell Biology, medicine, Autologous transplantation, METAANALYSIS, Transplantation, Antineoplastic Combined Chemotherapy Protocol, Hormonal, business.industry, medicine.disease, Surgery, business, Settore MED/15 - Malattie del Sangue
Abstract

In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.

Published
2012

48. The balance of proteasome load vs. capacity determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition

Author

BIANCHI G, OLIVA O, PAOLO CASCIO P, PENGO N, FONTANA F, CERRUTI F, ORSI A, PASQUALETTO E, MEZGHRANI A, CALBI V, PALLADINI G, GIULIANI N, ANDERSON KC, SITIA R, CENCI S, Bianchi, G, Oliva, O, PAOLO CASCIO, P, Pengo, N, Fontana, F, Cerruti, F, Orsi, A, Pasqualetto, E, Mezghrani, A, Calbi, V, Palladini, G, Giuliani, N, Anderson, Kc, Sitia, R, and Cenci, S

Subjects
PROTEOSTASIS, MYELOMA, PROTEASOME INHIBITORS
Abstract

Proteasome inhibitors (PIs) are effective against multiple myeloma (MM), but the mechanisms of action and bases of individual susceptibility remain unclear. Recent work linked PI sensitivity to protein synthesis and proteasome activity, raising the question whether different levels of proteasome expression and workload underlie PI sensitivity inMMcells (MMCs). Exploiting human MM lines characterized by differential PI sensitivity, we reportthat highly sensitive MMCs express lower proteasome levels and higher proteasomal workload than relatively PI-resistant MMCs, resulting in the accumulation of polyubiquitinated proteins at the expense of free ubiquitin (proteasome stress). Manipulating proteasome expression or workload alters apoptotic sensitivity to PI, demonstrating a cause-effect relationship between proteasome stress and apoptotic responses in MMCs. Intracellular immunostaining in primary, patient-derived MMCs reveals that polyubiquitinated proteins hallmark neoplastic plasmacells, in positive correlation with immunoglobulin (Ig) content, both intra- and interpatient. Moreover, overall proteasome activity of primary MMCs inversely correlates with apoptotic sensitivity to PI. Altogether,our data indicate that the balance between proteasome workload and degradative capacity represents a critical determinant of apoptotic sensitivity of MMCs to PI, potentially providing a framework for identifying indicators of responsiveness and designing novel combination therapies. (Blood. 2009;113:3040-3049)

Published
2009

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