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1. Deferasirox in the management of iron overload in patients with myelofibrosis treated with ruxolitinib: The multicentre retrospective RUX-IOL study

Author

Elli, E, Di Veroli, A, Bartoletti, D, Iurlo, A, Carmosino, I, Benevolo, G, Abruzzese, E, Bonifacio, M, Bergamaschi, M, Polverelli, N, Caramella, M, Cilloni, D, Tiribelli, M, Pugliese, N, Caocci, G, Crisa, E, Porrini, R, Markovic, U, Renso, R, Auteri, G, Cattaneo, D, Trawinska, M, Scaffidi, L, Biale, L, Bucelli, C, Breccia, M, Gambacorti Passerini, C, Palumbo, G, Latagliata, R, Palandri, F, Elli E. M., Di Veroli A., Bartoletti D., Iurlo A., Carmosino I., Benevolo G., Abruzzese E., Bonifacio M., Bergamaschi M., Polverelli N., Caramella M., Cilloni D., Tiribelli M., Pugliese N., Caocci G., Crisa E., Porrini R., Markovic U., Renso R., Auteri G., Cattaneo D., Trawinska M. M., Scaffidi L., Biale L., Bucelli C., Breccia M., Gambacorti Passerini C., Palumbo G. A., Latagliata R., Palandri F., Elli, E, Di Veroli, A, Bartoletti, D, Iurlo, A, Carmosino, I, Benevolo, G, Abruzzese, E, Bonifacio, M, Bergamaschi, M, Polverelli, N, Caramella, M, Cilloni, D, Tiribelli, M, Pugliese, N, Caocci, G, Crisa, E, Porrini, R, Markovic, U, Renso, R, Auteri, G, Cattaneo, D, Trawinska, M, Scaffidi, L, Biale, L, Bucelli, C, Breccia, M, Gambacorti Passerini, C, Palumbo, G, Latagliata, R, Palandri, F, Elli E. M., Di Veroli A., Bartoletti D., Iurlo A., Carmosino I., Benevolo G., Abruzzese E., Bonifacio M., Bergamaschi M., Polverelli N., Caramella M., Cilloni D., Tiribelli M., Pugliese N., Caocci G., Crisa E., Porrini R., Markovic U., Renso R., Auteri G., Cattaneo D., Trawinska M. M., Scaffidi L., Biale L., Bucelli C., Breccia M., Gambacorti Passerini C., Palumbo G. A., Latagliata R., and Palandri F.

Abstract

Deferasirox (DFX) is used for the management of iron overload (IOL) in many haematological malignancies including myelofibrosis (MF). The ‘RUX-IOL’ study retrospectively collected 69 MF patients treated with ruxolitinib (RUX) and DFX for IOL to assess: safety, efficacy in term of iron chelation response (ICR) and erythroid response (ER), and impact on overall survival of the combination therapy. The RUX–DFX therapy was administered for a median time of 12.4 months (interquartile range 3.1–71.2). During treatment, 36 (52.2%) and 34 (49.3%) patients required RUX and DFX dose reductions, while eight (11.6%) and nine (13.1%) patients discontinued due to RUX- or DFX-related adverse events; no unexpected toxicity was reported. ICR and ER were achieved by 33 (47.8%) and 32 patients (46.4%) respectively. Thirteen (18.9%) patients became transfusion-independent. Median time to ICR and ER was 6.2 and 2 months respectively. Patients achieving an ER were more likely to obtain an ICR also (p = 0.04). In multivariable analysis, the absence of leukocytosis at baseline (p = 0.02) and achievement of an ICR at any time (p = 0.02) predicted improved survival. In many MF patients, the RUX–DFX combination provided ICR and ER responses that correlated with improved outcome in the absence of unexpected toxicities. This strategy deserves further clinical investigation.

Published
2022

2. SETD2 and histone H3 lysine 36 methylation deficiency in advanced systemic mastocytosis

Author

Martinelli, G, Mancini, M, De Benedittis, C, Rondoni, M, Papayannidis, C, Manfrini, M, Meggendorfer, M, Calogero, R, Guadagnuolo, V, Fontana, M C, Bavaro, L, Padella, A, Zago, E, Pagano, L, Zanotti, R, Scaffidi, L, Specchia, G, Albano, F, Merante, S, Elena, C, Savini, P, Gangemi, D, Tosi, P, Ciceri, F, Poletti, G, Riccioni, L, Morigi, F, Delledonne, M, Haferlach, T, Cavo, M, Valent, P, and Soverini, S

Published
2018
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3. P1010: RUXOLITINIB IN MYELODEPLETIVE MYELOFIBROSIS: RESPONSE, TOXICITY, AND OUTCOME

Author

Palandri, F., primary, Bartoletti, D., additional, Breccia, M., additional, Auteri, G., additional, Elli, E. M., additional, Trawinska, M. M., additional, Polverelli, N., additional, Tiribelli, M., additional, Benevolo, G., additional, Iurlo, A., additional, Tieghi, A., additional, Heidel, F. H., additional, Caocci, G., additional, Beggiato, E., additional, Binotto, G., additional, Cavazzini, F., additional, Miglino, M., additional, Bosi, C., additional, Crugnola, M., additional, Bocchia, M., additional, Martino, B., additional, Pugliese, N., additional, Romagnoli, A. D., additional, Mazzoni, C., additional, Scaffidi, L., additional, Isidori, A., additional, Cattaneo, D., additional, Krampera, M., additional, Pane, F., additional, Cilloni, D., additional, Semenzato, G., additional, Lemoli, R. M., additional, Cuneo, A., additional, Abruzzese, E., additional, Vianelli, N., additional, Cavo, M., additional, Bonifacio, M., additional, and Palumbo, G. A., additional

Published
2022
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4. P993: SETD2 IS A BONA FIDE TUMOR SUPPRESSOR IN SYSTEMIC MASTOCYTOSIS

Author

Mancini, M., primary, Monaldi, C., additional, De Santis, S., additional, Papayannidis, C., additional, Rondoni, M., additional, Sartor, C., additional, Bruno, S., additional, Curti, A., additional, Zanotti, R., additional, Bonifacio, M., additional, Scaffidi, L., additional, Pagano, L., additional, Criscuolo, M., additional, Ciceri, F., additional, Elena, C., additional, Tosi, P., additional, Valent, P., additional, Cavo, M., additional, and Soverini, S., additional

Published
2022
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5. Carnevali storici della Campania e itinerari degli eventi rituali: analisi e rappresentazione in ambiente GIS

Author

Acierno A., De Toro P., Fierro N., Pistone I., Scaffidi L., Cardone B., Di Martino F., Acierno, A., De Toro, P., Fierro, N., Pistone, I., and Scaffidi, L.

Subjects
Aree interne, carnevali storici, spatial database, analisi geo-statistiche
Abstract

La Campania presenta un gran numero di carnevali storici, distribuiti nelle sue cinque provincie. Nell’ambito del Progetto di Ricerca dal titolo "Festività storiche dei carnevali della Campania. Gli itinerari urbani dei rituali storici: una proposta di candidatura UNESCO", sono stati studiati 104 festività. Il presente contributo si fonda sull’integrazione dei risultati ottenuti dal gruppo di ricerca, proponendo delle elaborazioni tematiche e utilizzando lo "spatial database" disponibile, nonché presentando nel dettaglio gli itinerari percorsi da alcuni carnevali. L’analisi spaziale ha riguardato, in particolare, analisi geo-statistiche elaborate in ambiente GIS in base ai temi riguardanti gli enti organizzatori, gli anni di origine, il rituale cerimoniale, le tipologie di rito, gli spazi collettivi coinvolti e il tipo di itinerario delle festività coinvolte dalla ricerca. Questo ha consentito di individuare la “concentrazione” di determinate tipologie di uso dello spazio urbano o di particolari riti tradizionali, nonché l’esistenza o meno di cluster tematici. Successivamente vengono descritte le caratteristiche degli itinerari dei carnevali, con il supporto di mappe geografiche che evidenziano le relazioni tra percorsi e luoghi. Le manifestazioni carnevalesche sono, infatti, intimamente legate ai luoghi in cui si svolgono, generando una significativa relazione tra lo spazio fisico e le rappresentazioni dei rituali storici, spesso riferiti alle aree interne della Campania.

Published
2021

7. Arterial thrombosis in Philadelphia-negative myeloproliferative neoplasms predicts second cancer: A case-control study

Author

De Stefano, V., Ghirardi, A., Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., Rossi, E., Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Finazzi, G., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., Elli, E. M., Palova, M., Rapezzi, D., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benevolo, G., Carli, G., Cacciola, R., McMullin, M. F., Tieghi, A., Recasens, V., Isfort, S., Marchetti, M., Griesshammer, M., Alvarez-Larran, A., Vannucchi, A. M., Rambaldi, A., Barbui, T., De Stefano V. (ORCID:0000-0002-5178-5827), Rossi E. (ORCID:0000-0002-7572-9379), De Stefano, V., Ghirardi, A., Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., Rossi, E., Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Finazzi, G., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., Elli, E. M., Palova, M., Rapezzi, D., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benevolo, G., Carli, G., Cacciola, R., McMullin, M. F., Tieghi, A., Recasens, V., Isfort, S., Marchetti, M., Griesshammer, M., Alvarez-Larran, A., Vannucchi, A. M., Rambaldi, A., Barbui, T., De Stefano V. (ORCID:0000-0002-5178-5827), and Rossi E. (ORCID:0000-0002-7572-9379)

Abstract

Patients with Philadelphia-negative myeloproliferative neoplasm (MPN) are prone to the development of second cancers, but the factors associated with these events have been poorly explored. In an international nested case-control study, we recruited 647 patients with carcinoma, nonmelanoma skin cancer, hematological second cancer, and melanoma diagnosed concurrently or after MPN diagnosis. Up to 3 control patients without a history of cancer and matched with each case for center, sex, age at MPN diagnosis, date of diagnosis, and MPN disease duration were included (n 5 1234). Cases were comparable to controls for MPN type, driver mutations and cardiovascular risk factors. The frequency of thrombosis preceding MPN was similar for cases and controls (P 5 .462). Thrombotic events after MPN and before second cancer were higher in cases than in controls (11.6% vs 8.1%; P 5 .013), because of a higher proportion of arterial thromboses (6.2% vs 3.7%; P 5 .015). After adjustment for confounders, the occurrence of arterial thrombosis remained independently associated with the risk of carcinoma (odds ratio, 1.97; 95% confidence interval, 1.14-3.41), suggesting that MPN patients experiencing arterial events after MPN diagnosis deserve careful clinical surveillance for early detection of carcinoma.

Published
2020

8. Reply to: Second primary malignancies in myeloproliferative neoplasms and the role of aspirin

Author

Barbui, T., Ghirardi, A., Vannucchi, A. M., Marchetti, M., De Stefano, Valerio, Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Finazzi, G., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., Elli, E. M., Palova, M., Bertolotti, L., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benevolo, G., Carli, G., Cacciola, R., Mcmullin, M. F., Tieghi, A., Recasens, V., Isfort, S., Griesshammer, M., Alvarez-Larran, A., Rambaldi, A., De Stefano V. (ORCID:0000-0002-5178-5827), Barbui, T., Ghirardi, A., Vannucchi, A. M., Marchetti, M., De Stefano, Valerio, Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Finazzi, G., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., Elli, E. M., Palova, M., Bertolotti, L., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benevolo, G., Carli, G., Cacciola, R., Mcmullin, M. F., Tieghi, A., Recasens, V., Isfort, S., Griesshammer, M., Alvarez-Larran, A., Rambaldi, A., and De Stefano V. (ORCID:0000-0002-5178-5827)

Abstract

N/A

Published
2020

9. Second cancers in MPN: Survival analysis from an international study

Author

Marchetti, M., Ghirardi, A., Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., Rossi, Elena, Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Finazzi, G., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., Elli, E. M., Palova, M., Rapezzi, D., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benevolo, G., Carli, G., Cacciola, R., Mcmullin, M. F., Tieghi, A., Recasens, V., Isfort, S., Pane, F., De Stefano, Valerio, Griesshammer, M., Alvarez-Larran, A., Vannucchi, A. M., Rambaldi, A., Barbui, T., Rossi E. (ORCID:0000-0002-7572-9379), De Stefano V. (ORCID:0000-0002-5178-5827), Marchetti, M., Ghirardi, A., Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., Rossi, Elena, Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Finazzi, G., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., Elli, E. M., Palova, M., Rapezzi, D., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benevolo, G., Carli, G., Cacciola, R., Mcmullin, M. F., Tieghi, A., Recasens, V., Isfort, S., Pane, F., De Stefano, Valerio, Griesshammer, M., Alvarez-Larran, A., Vannucchi, A. M., Rambaldi, A., Barbui, T., Rossi E. (ORCID:0000-0002-7572-9379), and De Stefano V. (ORCID:0000-0002-5178-5827)

Abstract

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A “poor prognosis” SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a “non-poor prognosis” SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.

Published
2020

10. Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study

Author

Barbui, T., Ghirardi, A., Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., De Stefano, Valerio, Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Delaini, F., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., Elli, E. M., Palova, M., Bertolotti, L., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benevolo, G., Carli, G., Cacciola, R., Mcmullin, M. F., Tieghi, A., Recasens, V., Marchetti, M., Griesshammer, M., Alvarez-Larran, A., Vannucchi, A. M., Finazzi, G., De Stefano V. (ORCID:0000-0002-5178-5827), Barbui, T., Ghirardi, A., Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., De Stefano, Valerio, Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Delaini, F., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., Elli, E. M., Palova, M., Bertolotti, L., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benevolo, G., Carli, G., Cacciola, R., Mcmullin, M. F., Tieghi, A., Recasens, V., Marchetti, M., Griesshammer, M., Alvarez-Larran, A., Vannucchi, A. M., Finazzi, G., and De Stefano V. (ORCID:0000-0002-5178-5827)

Abstract

We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82–1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15–4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00–14.01), ruxolitinib (OR = 3.87, 95% CI 1.18–12.75), and for drug combination (OR = 3.47, 95% CI 1.55–7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.

Published
2019

11. Risk factors for secondary cancer in a case-control study on 1,881 patients with myeloproliferative neoplasms (ELN Study)

Author

Barbui, T., Ghirardi, A., Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., Destefano, V., Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Delaini, F., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Stephensom, C., Guglielmelli, P., Elli, E. M., Miroslava, P., Bertolotti, L., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benelovo, G., Carli, G., Cacciola, R., Mcmullin, M. F., Tieghi, A., Rcasens Flores, V., Marchetti, M., Griesshammer, M., Alvarez-Larran, A., Vannucchi, A., and Finazzi, G.

Published
2018

12. Reply to: Second primary malignancies in myeloproliferative neoplasms and the role of aspirin

Author

Barbui, T., Ghirardi, A., Vannucchi, A. M., Marchetti, M., De Stefano, Valerio, Masciulli, A., Carobbio, A., Palandri, F., Vianelli, N., Betti, S., Di Veroli, A., Iurlo, A., Cattaneo, D., Finazzi, G., Bonifacio, M., Scaffidi, L., Patriarca, A., Rumi, E., Casetti, I. C., Stephenson, C., Guglielmelli, P., Elli, E. M., Palova, M., Bertolotti, L., Erez, D., Gomez, M., Wille, K., Perez-Encinas, M., Lunghi, F., Angona, A., Fox, M. L., Beggiato, E., Benevolo, G., Carli, G., Cacciola, R., Mcmullin, M. F., Tieghi, A., Recasens, V., Isfort, S., Griesshammer, M., Alvarez-Larran, A., and Rambaldi, A.

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Aspirin, business.industry, Hematology, Second primary cancer, Settore MED/15 - MALATTIE DEL SANGUE, Internal medicine, medicine, business, Myelopriferative neoplasms, medicine.drug
Published
2019

13. PF674 OUTCOME OF PATIENTS WITH MYELOFIBROSIS AFTER RUXOLITINIB DISCONTINUATION: ROLE OF DISEASE STATUS AND TREATMENT STRATEGIES IN 218 PATIENTS

Author

Palandri, F., primary, Breccia, M., additional, Bonifacio, M., additional, Polverelli, N., additional, Elli, E.M., additional, Benevolo, G., additional, Tiribelli, M., additional, Abruzzese, E., additional, Iurlo, A., additional, Heidel, F., additional, Bergamaschi, M., additional, Tieghi, A., additional, Crugnola, M., additional, Cavazzini, F., additional, Binotto, G., additional, Isidori, A., additional, Sgherza, N., additional, Bosi, C., additional, Martino, B., additional, Latagliata, R., additional, Auteri, G., additional, Scaffidi, L., additional, Griguolo, D., additional, Trawinska, M., additional, Cattaneo, D., additional, Catani, L., additional, Krampera, M., additional, Vitolo, U., additional, Lemoli, R.M., additional, Cuneo, A., additional, Semenzato, G., additional, Foà, R., additional, Raimondo, F. Di, additional, Bartoletti, D., additional, Cavo, M., additional, Palumbo, G.A., additional, and Vianelli, N., additional

Published
2019
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14. PS1468 IMPACT OF CYTOREDUCTIVE DRUGS ON SECOND CANCER IN MYELOPROLIFERATIVE NEOPLASMS

Author

Barbui, T., primary, Ghirardi, A., additional, Masciulli, A., additional, Carobbio, A., additional, Palandri, F., additional, Vianelli, N., additional, De Stefano, V., additional, Betti, S., additional, Di Veroli, A., additional, Iurlo, A., additional, Cattaneo, D., additional, Delaini, F., additional, Bonifacio, M., additional, Scaffidi, L., additional, Patriarca, A., additional, Rumi, E., additional, Stephenson, C., additional, Guglielmelli, P., additional, Elli, E.M., additional, Miroslava, P., additional, Bertolotti, L., additional, Erez, D., additional, Gomez, M., additional, Wille, K., additional, Perez-Encinas, M., additional, Lunghi, F., additional, Angona, A., additional, Fox, M.L., additional, Beggiato, E., additional, Benevolo, G., additional, Carli, G., additional, Cacciola, R., additional, McMullin, M.F., additional, Tieghi, A., additional, Recasens, V., additional, Marchetti, M., additional, Griesshammer, M., additional, Alvarez-Larran, A., additional, Vannucchi, A., additional, and Finazzi, G., additional

Published
2019
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15. PB1930 CORRELATION BETWEEN LEVELS OF EARLY MOLECULAR RESPONSE AND BCR-ABL TRANSCRIPT TYPE IN STABLE DMR ATTAINMENT IN CML PATIENTS TREATED WITH IMATINIB

Author

Tiribelli, M., primary, Bonifacio, M., additional, Binotto, G., additional, Griguolo, D., additional, Scaffidi, L., additional, Frison, L., additional, Miggiano, M.C., additional, Calistri, E., additional, Stulle, M., additional, De Biasi, E., additional, Sartori, R., additional, Stella, R., additional, Tanasi, I., additional, Ruggeri, M., additional, Damiani, D., additional, Semenzato, G., additional, Krampera, M., additional, and Fanin, R., additional

Published
2019
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16. PS1461 FAMILIAL OCCURRENCE OF SYSTEMIC AND CUTANEOUS MASTOCYTOSIS IN AN ADULT MULTICENTER SERIES: A REPORT OF 22 CLUSTERED CASES

Author

Tanasi, I., primary, Bonifacio, M., additional, Pizzolato, M., additional, Grifoni, F.I., additional, Sciumè, M., additional, Elena, C., additional, Benvenuti, P., additional, Mannelli, F., additional, Parente, R., additional, Schena, D., additional, Scaffidi, L., additional, Bonadonna, P., additional, Papayannidis, C., additional, Rondoni, M., additional, Criscuolo, M., additional, Vannucchi, A.M., additional, Triggiani, M., additional, Martinelli, G., additional, Krampera, M., additional, and Zanotti, R., additional

Published
2019
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17. Short and Long-Term Risk of Major Cardiovascular Events after Ischemic Stroke or Transient Ischemic Attack in Myeloproliferative Neoplasms

Author

Barbui, T, De Stefano, V, Carobbio, A, Di Lazzaro, V, Guglielmelli, P, Iurlo, A, Finazzi, M, Rumi, E, Cervantes, F, Elli, E, Randi, Ml, Griesshammer, M, Palandri, F, Bonifacio, M, Hernandez, E, Cacciola, Rossella Rosaria, Cacciola, E, Palova, M, Carli, G, Beggiato, E, Martinelli, E, Musolino, C, Gaidano, G, Tieghi, A, Lunghi, F, Loscocco, G, Cattaneo, D, Cortelezzi, A, Betti, S, Rossi, E, Finazzi, G, Censori, B, Cazzola, M, Bellini, M, Arellano, V, Bertozzi, I, Sadiadian, P, Vianelli, N, and Scaffidi, L.

Published
2017

18. SETD2 and histone H3 lysine 36 methylation deficiency in advanced systemic mastocytosis

Author

Martinelli, G, primary, Mancini, M, additional, De Benedittis, C, additional, Rondoni, M, additional, Papayannidis, C, additional, Manfrini, M, additional, Meggendorfer, M, additional, Calogero, R, additional, Guadagnuolo, V, additional, Fontana, M C, additional, Bavaro, L, additional, Padella, A, additional, Zago, E, additional, Pagano, L, additional, Zanotti, R, additional, Scaffidi, L, additional, Specchia, G, additional, Albano, F, additional, Merante, S, additional, Elena, C, additional, Savini, P, additional, Gangemi, D, additional, Tosi, P, additional, Ciceri, F, additional, Poletti, G, additional, Riccioni, L, additional, Morigi, F, additional, Delledonne, M, additional, Haferlach, T, additional, Cavo, M, additional, Valent, P, additional, and Soverini, S, additional

Published
2017
Full Text
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21. Imatinib-treated Chronic Myeloid Leukemia patients with discordant response between cytogenetic and molecular tests at 3 and 6 month time-points have a reduced probability of subsequent optimal response

Author

Bonifacio, M., primary, Binotto, G., additional, Maino, E., additional, Calistri, E., additional, Marin, L., additional, Scaffidi, L., additional, Frison, L., additional, De Marchi, F., additional, Krampera, M., additional, Semenzato, G., additional, Fanin, R., additional, Ambrosetti, A., additional, and Tiribelli, M., additional

Published
2015
Full Text
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26. COMORBIDITIES AND BODY MASS INDEX IMPACT ON SURVIVAL IN PATIENTS WITH MYELOFIBROSIS TREATED WITH RUXOLITINIB

Author

Breccia, M., Tiribelli, M., Bonifacio, M., Palumbo, G. A., Alessia Tieghi, Polverelli, N., Bergamaschi, M., Cavazzini, F., Isidori, A., Binotto, G., Cimino, G., D Adda, M., Crugnola, M., Bosi, C., Sgherza, N., Spinsanti, M., Molica, M., Fama, A., Cerqui, E., Lazzaro, A., Scaffidi, L., Colafigli, G., Latagliata, R., Fanin, R., Russo, D., Aversa, F., Cuneo, A., Cavo, M., Vianelli, N., Foa, R., and Palandri, F.

27. SECOND PRIMARY MALIGNANCY IN MYELOFIBROSIS PATIENTS TREATED WITH RUXOLITINIB

Author

Polverelli, N., Elli, E., Abruzzese, E., Palumbo, G. A., Benevolo, G., Breccia, M., Tiribelli, M., Bonifacio, M., Tieghi, A., Martino, B., Sgherza, N., D Adda, M., Bergamaschi, M., Crugnola, M., Cavazzini, F., Bosi, C., Binotto, G., Isidori, A., Bartoletti, D., Auteri, G., Latagliata, R., Gandolfi, L., Scaffidi, L., Cattaneo, D., Codeluppi, K., Trawinska, M., Griguolo, D., Cuneo, A., Krampera, M., Semenzato, G., Di Raimondo, F., Lemoli, R. M., Cavo, M., Vianelli, N., Russo, D., Iurlo, A., and FRANCESCA PALANDRI

28. IMPACT OF COMORBIDITIES AND BODY MASS INDEX ON SURVIVAL IN PATIENTS WITH MYELOFIBROSIS TREATED WITH RUXOLITINIB

Author

Palandri, F., Tiribelli, M., Bonifacio, M., Palumbo, G. A., Tieghi, A., Nicola Polverelli, Bergamaschi, M., Cavazzini, F., Isidori, A., Binotto, G., Cimino, G., D Adda, M., Crugnola, M., Bosi, C., Sgherza, N., Spinsanti, M., Molica, M., Fama, A., Andriani, A., Cerqui, E., Lazzaro, A., Scaffidi, L., Massaro, F., Latagliata, R., Fanin, R., Russo, D., Aversa, F., Cuneo, A., Cavo, M., Vianelli, N., and Breccia, M.

29. PREDICTORS FOR RESPONSE TO RUXOLITINIB IN REAL-LIFE: AN OBSERVATIONAL INDEPENDENT STUDY ON 266 PATIENTS WITH MYELOFIBROSIS

Author

Polverelli, N., Benevolo, G., Palumbo, G. A., Bonifacio, M., Tiribelli, M., Martino, B., Alessia Tieghi, Breccia, M., Ibatici, A., Crugnola, M., Bosi, C., Catani, L., Scaffidi, L., Marchi, F., Lazzaro, A., Aversa, F., Di Raimondo, F., Vallisa, D., Vitolo, U., Merli, F., Fanin, R., Alimena, G., Martinelli, G., Cavo, M., Vianelli, N., and Palandri, F.

Subjects
ruxolitinib, predictors of outcome, myelofibrosis, ruxolitinib, myelofibrosis, predictors of outcome

31. Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial

Author

Alberto Ferrari, Cristina Bucelli, Elisa Rumi, Barbara Mora, Alessandra Carobbio, Fabrizio Pane, Tiziano Barbui, Gianni Tognoni, Andrea Patriarca, Francesca Palandri, Giuseppe Carli, Nicola Cascavilla, Elena Rossi, Sergio Siragusa, Alessandra Iurlo, Giuseppe Gaetano Loscocco, Fabio Ciceri, Maria Chiara Finazzi, Alessandro M. Vannucchi, Davide Rapezzi, Carmela Mannarelli, Giulia Benevolo, Arianna Masciulli, Marianna Caramella, Luigi Scaffidi, Arianna Ghirardi, Nicola Vianelli, Silvia Betti, Massimiliano Bonifacio, Alessandro Rambaldi, Valerio De Stefano, Marta Bellini, Paola Guglielmelli, Francesca Lunghi, Emma Cacciola, Alessandra Ricco, Caterina Musolino, Barbui T., Vannucchi A.M., De Stefano V., Masciulli A., Carobbio A., Ferrari A., Ghirardi A., Rossi E., Ciceri F., Bonifacio M., Iurlo A., Palandri F., Benevolo G., Pane F., Ricco A., Carli G., Caramella M., Rapezzi D., Musolino C., Siragusa S., Rumi E., Patriarca A., Cascavilla N., Mora B., Cacciola E., Mannarelli C., Loscocco G.G., Guglielmelli P., Betti S., Lunghi F., Scaffidi L., Bucelli C., Vianelli N., Bellini M., Finazzi M.C., Tognoni G., Rambaldi A., Barbui, T., Vannucchi, A. M., De Stefano, V., Masciulli, A., Carobbio, A., Ferrari, A., Ghirardi, A., Rossi, E., Ciceri, F., Bonifacio, M., Iurlo, A., Palandri, F., Benevolo, G., Pane, F., Ricco, A., Carli, G., Caramella, M., Rapezzi, D., Musolino, C., Siragusa, S., Rumi, E., Patriarca, A., Cascavilla, N., Mora, B., Cacciola, E., Mannarelli, C., Loscocco, G. G., Guglielmelli, P., Betti, S., Lunghi, F., Scaffidi, L., Bucelli, C., Vianelli, N., Bellini, M., Finazzi, M. C., Tognoni, G., and Rambaldi, A.

Subjects
Adult, Male, medicine.medical_specialty, Polycythaemia, Neutropenia, Adolescent, Policithemia vera, Interferon alpha-2, Polymorphism, Single Nucleotide, law.invention, Polyethylene Glycols, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Randomized controlled trial, Phlebotomy, law, Bone Marrow, Internal medicine, medicine, Clinical endpoint, Data monitoring committee, Humans, Polycythemia Vera, business.industry, Standard treatment, Interferon-alpha, Hematology, Janus Kinase 2, Middle Aged, Interim analysis, medicine.disease, Recombinant Proteins, Regimen, Treatment Outcome, 030220 oncology & carcinogenesis, Quality of Life, Female, business, 030215 immunology
Abstract

Summary Background There is no evidence that phlebotomy alone is sufficient to steadily maintain haematocrit on target level in low-risk patients with polycythaemia vera. This study aimed to compare the efficacy and safety of ropeginterferon alfa-2b on top of the standard phlebotomy regimen with phlebotomy alone. Methods In 2017, we launched the Low-PV study, a multicentre, open-label, two-arm, parallel-group, investigator-initiated, phase 2 randomised trial with a group-sequential adaptive design. The study involved 21 haematological centres across Italy. Participants were recruited in a consecutive order. Participants enrolled in the study were patients, aged 18–60 years, with a diagnosis of polycythaemia vera according to 2008–16 WHO criteria. Eligible patients were randomly allocated (1:1) to receive either phlebotomy and low-dose aspirin (standard group) or ropeginterferon alfa-2b on top of the standard treatment (experimental group). Randomisation sequence was generated using five blocks of variable sizes proportional to elements of Pascal's triangle. Allocation was stratified by age and time from diagnosis. No masking was done. Patients randomly allocated to the standard group were treated with phlebotomy (300 mL for each phlebotomy to maintain the haematocrit values of lower than 45%) and low-dose aspirin (100 mg daily), if not contraindicated. Patients randomly allocated to the experimental group received ropeginterferon alfa-2b subcutaneously every 2 weeks in a fixed dose of 100 μg on top of the phlebotomy-only regimen. The primary endpoint was treatment response, defined as maintenance of the median haematocrit values of 45% or lower without progressive disease during a 12-month period. Analyses were done by intention-to-treat principle. The study was powered assuming a higher percentage of responders in the experimental group (75%) than in the standard group (50%). Here we report results from the second planned interim analysis when 50 patients had been recruited to each group. The trial is ongoing, and registered with ClinicalTrials.gov , NCT03003325 . Findings Between Feb 2, 2017, and March 13, 2020, 146 patients were screened, and 127 patients were randomly assigned to the standard group (n=63) or the experimental group (n=64). The median follow-up period was 12·1 months (IQR 12·0–12·6). For the second pre-planned interim analysis, a higher response rate in the experimental group was seen (42 [84%] of 50 patients) than in the standard group (30 [60%] of 50 patients; absolute difference 24%, 95% CI 7–41%, p=0·0075). The observed z value (2·6001) crossed the critical bound of efficacy (2·5262), and the stagewise adjusted p value early showed superiority of experimental treatment. Thus, the data safety monitoring board decided to stop patient accrual for overwhelming efficacy and to continue the follow-up, as per protocol, for 2 years. Under the safety profile, no statistically significant difference between groups in frequency of adverse events of grade 3 or higher was observed; the most frequently reported adverse events were neutropenia (four [8%] of 50 patients) in the experimental group and skin symptoms (two [4%] of 50 patients) in the standard group. No grade 4 or 5 adverse events occurred. Interpretation Supplementing phlebotomy with ropeginterferon alfa-2b seems to be safe and effective in steadily maintaining haematocrit values on target in low-risk patients with polycythaemia vera. Findings from the current study might have implications for changing the current management of low-risk patients with polycythaemia vera. Funding AOP Orphan Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro

Published
2020

32. SETD2 and histone H3 lysine 36 methylation deficiency in advanced systemic mastocytosis

Author

T Haferlach, Livio Pagano, Massimo Delledonne, Simona Soverini, Antonella Padella, Fabio Ciceri, Patrizia Tosi, L Riccioni, Marco Manfrini, Giovanni Martinelli, Manja Meggendorfer, Serena Merante, F Morigi, C De Benedittis, Domenica Gangemi, Luana Bavaro, Michela Rondoni, Manuela Mancini, Roberta Zanotti, Paolo Savini, Viviana Guadagnuolo, Giovanni Poletti, Michele Cavo, Maria Chiara Fontana, Luigi Scaffidi, Chiara Elena, Giorgina Specchia, Francesco Albano, Elisa Zago, Peter Valent, Raffaele A. Calogero, Cristina Papayannidis, Martinelli, G., Mancini, M., De Benedittis, C., Rondoni, M., Papayannidis, C., Manfrini, M., Meggendorfer, M., Calogero, R., Guadagnuolo, V., Fontana, M. C., Bavaro, L., Padella, A., Zago, E., Pagano, L., Zanotti, R., Scaffidi, L., Specchia, G., Albano, F., Merante, S., Elena, C., Savini, P., Gangemi, D., Tosi, P., Ciceri, F., Poletti, G., Riccioni, L., Morigi, F., Delledonne, M., Haferlach, T., Cavo, M., Valent, P., Soverini, S., Martinelli, G, Mancini, M, De Benedittis, C, Rondoni, M, Papayannidis, C, Manfrini, M, Meggendorfer, M, Calogero, R, Guadagnuolo, V, Fontana, M. C, Bavaro, L, Padella, A, Zago, E, Pagano, L, Zanotti, R, Scaffidi, L, Specchia, G, Albano, F, Merante, S, Elena, C, Savini, P, Gangemi, D, Tosi, P, Ciceri, F, Poletti, G, Riccioni, L, Morigi, F, Delledonne, M, Haferlach, T, Cavo, M, and Valent, P

Subjects
0301 basic medicine, Adult, Male, Cancer Research, Proteasome Endopeptidase Complex, systemic mastocytosis, mast cell leukemia, SETD2, Apoptosis, Biology, Methylation, Histones, 03 medical and health sciences, chemistry.chemical_compound, Histone H3, Mastocytosis, Systemic, SETD2, Cell Line, Tumor, medicine, Humans, Midostaurin, Mast Cells, Systemic mastocytosis, Aged, Bortezomib, Lysine, leukemia, Hematology, Histone-Lysine N-Methyltransferase, Middle Aged, medicine.disease, Mast cell leukemia, Prognosis, Staurosporine, 3. Good health, Settore MED/15 - MALATTIE DEL SANGUE, 030104 developmental biology, Oncology, chemistry, Histone methyltransferase, Mutation, Cancer research, Female, Original Article, K562 Cells, Mastocytosis, medicine.drug
Abstract

The molecular basis of advanced systemic mastocytosis (SM) is not fully understood and despite novel therapies the prognosis remains dismal. Exome sequencing of an index-patient with mast cell leukemia (MCL) uncovered biallelic loss-of-function mutations in the SETD2 histone methyltransferase gene. Copy-neutral loss-of-heterozygosity at 3p21.3 (where SETD2 maps) was subsequently found in SM patients and prompted us to undertake an in-depth analysis of SETD2 copy number, mutation status, transcript expression and methylation levels, as well as functional studies in the HMC-1 cell line and in a validation cohort of 57 additional cases with SM, including MCL, aggressive SM and indolent SM. Reduced or no SETD2 protein expression-and consequently, H3K36 trimethylation-was found in all cases and inversely correlated with disease aggressiveness. Proteasome inhibition rescued SETD2 expression and H3K36 trimethylation and resulted in marked accumulation of ubiquitinated SETD2 in SETD2-deficient patients but not in patients with near-normal SETD2 expression. Bortezomib and, to a lesser extent, AZD1775 alone or in combination with midostaurin induced apoptosis and reduced clonogenic growth of HMC-1 cells and of neoplastic mast cells from advanced SM patients. Our findings may have implications for prognostication of SM patients and for the development of improved treatment approaches in advanced SM.Leukemia advance online publication, 30 June 2017; doi:10.1038/leu.2017.183.

Published
2018

33. Deferasirox in the management of iron overload in patients with myelofibrosis treated with ruxolitinib: The multicentre retrospective RUX-IOL study

Author

Elena Maria Elli, Ambra Di Veroli, Daniela Bartoletti, Alessandra Iurlo, Ida Carmosino, Giulia Benevolo, Elisabetta Abruzzese, Massimiliano Bonifacio, Micaela Bergamaschi, Nicola Polverelli, Marianna Caramella, Daniela Cilloni, Mario Tiribelli, Novella Pugliese, Giovanni Caocci, Elena Crisà, Raffaele Porrini, Uros Markovic, Rossella Renso, Giuseppe Auteri, Daniele Cattaneo, Malgorzata Monika Trawinska, Luigi Scaffidi, Lucia Biale, Cristina Bucelli, Massimo Breccia, Carlo Gambacorti‐Passerini, Giuseppe Alberto Palumbo, Roberto Latagliata, Francesca Palandri, Elli, E, Di Veroli, A, Bartoletti, D, Iurlo, A, Carmosino, I, Benevolo, G, Abruzzese, E, Bonifacio, M, Bergamaschi, M, Polverelli, N, Caramella, M, Cilloni, D, Tiribelli, M, Pugliese, N, Caocci, G, Crisa, E, Porrini, R, Markovic, U, Renso, R, Auteri, G, Cattaneo, D, Trawinska, M, Scaffidi, L, Biale, L, Bucelli, C, Breccia, M, Gambacorti Passerini, C, Palumbo, G, Latagliata, R, and Palandri, F

Subjects
ruxolitinib, myelofibrosis, Hematology, Iron Chelating Agents, Benzoates, cancer, deferasirox, iron overload, Pyrimidines, myelofibrosi, MED/15 - MALATTIE DEL SANGUE, Primary Myelofibrosis, Nitriles, Humans, Pyrazoles, Retrospective Studies
Abstract

Deferasirox (DFX) is used for the management of iron overload (IOL) in many haematological malignancies including myelofibrosis (MF). The ‘RUX-IOL’ study retrospectively collected 69 MF patients treated with ruxolitinib (RUX) and DFX for IOL to assess: safety, efficacy in term of iron chelation response (ICR) and erythroid response (ER), and impact on overall survival of the combination therapy. The RUX–DFX therapy was administered for a median time of 12.4months (interquartile range 3.1–71.2). During treatment, 36 (52.2%) and 34 (49.3%) patients required RUX and DFX dose reductions, while eight (11.6%) and nine (13.1%) patients discontinued due to RUX- or DFX-related adverse events; no unexpected toxicity was reported. ICR and ER were achieved by 33 (47.8%) and 32 patients (46.4%) respectively. Thirteen (18.9%) patients became transfusion-independent. Median time to ICR and ER was 6.2 and 2months respectively. Patients achieving an ER were more likely to obtain an ICR also (p=0.04). In multivariable analysis, the absence of leukocytosis at baseline (p=0.02) and achievement of an ICR at any time (p=0.02) predicted improved survival. In many MF patients, the RUX–DFX combination provided ICR and ER responses that correlated with improved outcome in the absence of unexpected toxicities. This strategy deserves further clinical investigation.

Published
2022

34. Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis: Frequency, therapeutic effects, and impact on outcome

Author

Costanza Bosi, Nicola Vianelli, Fabrizio Pane, Giovanni Caocci, Massimiliano Bonifacio, Mario Tiribelli, Michele Cavo, Malgorzata Monika Trawinska, Daniela Bartoletti, Mauro Krampera, Giuseppe Auteri, Giulia Benevolo, Bruno Martino, Daniele Cattaneo, Roberto M. Lemoli, Giuseppe A. Palumbo, Nicola Polverelli, Massimo Breccia, Luigi Scaffidi, Monica Crugnola, Elisabetta Abruzzese, Antonio Cuneo, Florian H. Heidel, Elena Maria Elli, Elena Masselli, Francesca Palandri, Roberto Latagliata, Francesco Cavazzini, Alessandra Iurlo, Novella Pugliese, Rossella Stella, Giorgia Micucci, Alessia Tieghi, Gianpietro Semenzato, Gianni Binotto, Palandri F., Tiribelli M., Breccia M., Bartoletti D., Elli E.M., Benevolo G., Martino B., Cavazzini F., Tieghi A., Iurlo A., Abruzzese E., Pugliese N., Binotto G., Caocci G., Auteri G., Cattaneo D., Trawinska M.M., Stella R., Scaffidi L., Polverelli N., Micucci G., Masselli E., Crugnola M., Bosi C., Heidel F.H., Latagliata R., Pane F., Cuneo A., Krampera M., Semenzato G., Lemoli R.M., Cavo M., Vianelli N., Bonifacio M., and Palumbo G.A.

Subjects
Cancer Research, medicine.medical_specialty, Disease status, Ruxolitinib, ruxolitinib, rechallenge, myelofibrosis, NO, 03 medical and health sciences, 0302 clinical medicine, myelofibrosi, Internal medicine, Nitriles, Overall survival, Medicine, cancer, Humans, In patient, 030212 general & internal medicine, Myelofibrosis, Retrospective Studies, outcome, business.industry, Therapeutic effect, Retrospective cohort study, medicine.disease, Discontinuation, Pyrimidines, Treatment Outcome, Oncology, Primary Myelofibrosis, 030220 oncology & carcinogenesis, Pyrazoles, business, medicine.drug
Abstract

BACKGROUND: After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities. METHODS: The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival. RESULTS: A total of 219 patients (31.2%) discontinued ruxolitinib for ≥14 days and survived for ≥30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for ≥14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P =.004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P 10 mg twice daily predicted better spleen (P =.05) and symptom improvements (P =.02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P =.004). CONCLUSIONS: Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.

Published
2021

35. Low-density lipoprotein (LDL) levels and risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib

Author

Fabio Stagno, Patrizia Pregno, Giovanni Caocci, Gianni Binotto, Robin Foà, Anna Sicuranza, Emilia Scalzulli, Francesca Pirillo, Mario Tiribelli, Isabella Capodanno, Antonella Gozzini, Massimiliano Bonifacio, Rossella Stella, Elisabetta Abruzzese, Massimo Breccia, Claudio Fozza, Gabriele Gugliotta, Giorgio La Nasa, Luigiana Luciano, Olga Mulas, Maria Pina Simula, Daniele Cattaneo, Mario Annunziata, Francesco Albano, Luigi Scaffidi, Fiorenza De Gregorio, Debora Luzi, Claudia Baratè, Malgorzata Monika Trawinska, Immacolata Attolico, Fabio Efficace, Sara Galimberti, Fausto Castagnetti, Monica Bocchia, Bruno Martino, Alessandra Iurlo, Caocci G., Mulas O., Capodanno I., Bonifacio M., Annunziata M., Galimberti S., Luciano L., Tiribelli M., Martino B., Castagnetti F., Binotto G., Pregno P., Stagno F., Abruzzese E., Bocchia M., Gozzini A., Albano F., Fozza C., Luzi D., Efficace F., Simula M.P., Scaffidi L., Barate C., De Gregorio F., Stella R., Gugliotta G., Pirillo F., Trawinska M.M., Sicuranza A., Cattaneo D., Attolico I., Scalzulli E., Iurlo A., Foa R., Breccia M., and La Nasa G.

Subjects
Male, Arterial Occlusive Disease, Triglyceride, Gastroenterology, Antineoplastic Agent, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, 80 and over, Cumulative incidence, Chronic, Aged, 80 and over, Leukemia, Incidence (epidemiology), Chronic myeloid leukemia, Hematology, General Medicine, Middle Aged, Lipoproteins, LDL, Cholesterol, 030220 oncology & carcinogenesis, Low-density lipoprotein, Female, Human, medicine.drug, Adult, medicine.medical_specialty, Lipoproteins, Arterial occlusive event, Antineoplastic Agents, Arterial Occlusive Diseases, Lower risk, High cholesterol, LDL, 03 medical and health sciences, Young Adult, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Triglycerides, Aged, Dyslipidemias, business.industry, Risk Factor, Nilotinib, medicine.disease, Pyrimidines, Dyslipidemia, Pyrimidine, chemistry, BCR-ABL Positive, business, 030215 immunology, Myelogenous
Abstract

Recommendations for dyslipidemia management aimed at reducing arterial occlusive events (AOEs) have been recently published. So far, no data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib. We investigated 369 CML adult patients, stratified according to the new Systematic Coronary Risk Evaluation (SCORE) scoring system. Plasma levels of cholesterol, HDL, LDL, and triglycerides were measured prior to the start of nilotinib and after 3, 6, and 12months. The 5-year cumulative incidence of AOEs was 15.9%. Patients with cholesterol levels > 200mg/dL and LDL > 70mg/dL 3months after treatment showed a significantly higher incidence of AOEs (21.9 ± 4.6% vs 6.2 ± 2.5, P= 0.003). Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (34.4 ± 6% vs 10 ± 2.1%, P< 0.001). In multivariate analysis, both high cholesterol and LDL levels and a high and very high SCORE risk remained significantly associated with the risk of AOEs (P= 0.008; HR = 3.5; 95% CI = 1.4–8.7 and P < 0.001; HR = 4.4; 95% CI = 2–9.8, respectively). Overall, 78 patients (21.1%) presented dyslipidemia at the time of CML diagnosis and 88 (23.3%) after starting nilotinib, but only 26 of them (29.5%) were treated with statins. Low LDL and cholesterol plasma levels are associated with a significant lower risk of AOEs in CML patients treated with nilotinib in the real life.

Published
2020

36. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis

Author

Bruno Martino, Daniele Cattaneo, Florian H. Heidel, Elisabetta Abruzzese, Gianni Binotto, Rossella Stella, Giulia Benevolo, Michele Cavo, Micaela Bergamaschi, Roberto Latagliata, Francesco Cavazzini, Novella Pugliese, Massimo Breccia, Alessandro Isidori, Gianpietro Semenzato, Daniela Bartoletti, Mauro Krampera, Malgorzata Monica Trawinska, Costanza Bosi, Giovanni Caocci, Fabrizio Pane, Alessia Tieghi, Francesca Palandri, Roberto M. Lemoli, Elena Maria Elli, Antonio Cuneo, Fiorella Ciantia, Alessandra Iurlo, Monica Crugnola, Giuseppe Auteri, Mario Tiribelli, Massimiliano Bonifacio, Nicola Vianelli, Luigi Scaffidi, Giuseppe A. Palumbo, Nicola Polverelli, Palandri F., Palumbo G.A., Elli E.M., Polverelli N., Benevolo G., Martino B., Abruzzese E., Tiribelli M., Tieghi A., Latagliata R., Cavazzini F., Bergamaschi M., Binotto G., Crugnola M., Isidori A., Caocci G., Heidel F., Pugliese N., Bosi C., Bartoletti D., Auteri G., Cattaneo D., Scaffidi L., Trawinska M.M., Stella R., Ciantia F., Pane F., Cuneo A., Krampera M., Semenzato G., Lemoli R.M., Iurlo A., Vianelli N., Cavo M., Breccia M., and Bonifacio M.

Subjects
Ruxolitinib, medicine.medical_specialty, Humans, Janus Kinases, Multivariate Analysis, Primary Myelofibrosis, Protein Kinase Inhibitors, Pyrazoles, Risk Factors, Treatment Outcome, medicine.medical_treatment, Splenectomy, lcsh:RC254-282, Nitriles, Pyrimidines, Ruxolitinib discontinuation syndrome, risk factors, myelofibrosis, NO, Myeloproliferative disease, Internal medicine, Correspondence, medicine, Risk factor, Bone pain, Myelofibrosis, Respiratory distress, business.industry, Incidence (epidemiology), Hematology, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Discontinuation, Oncology, medicine.symptom, business, Haematological diseases, medicine.drug
Abstract

No abstract available

Published
2020

37. Renin angiotensin system inhibitors reduce the incidence of arterial thrombotic events in patients with hypertension and chronic myeloid leukemia treated with second- or third-generation tyrosine kinase inhibitors

Author

Chiara Elena, Alessandra Iurlo, Antonella Gozzini, Giorgio La Nasa, Claudia Baratè, Gabriele Gugliotta, Bruno Martino, Francesca Pirillo, Fiorenza De Gregorio, Fabio Efficace, Monica Bocchia, Massimo Breccia, Claudio Fozza, Elisabetta Abruzzese, Mario Annunziata, Sara Galimberti, Gianni Binotto, Fabio Stagno, Isabella Capodanno, Malgorzata Monika Trawinska, Anna Sicuranza, Maria Pina Simula, Robin Foà, Debora Luzi, Patrizia Pregno, Rossella Stella, Imma Attolico, Luigiana Luciano, Francesco Albano, Giovanni Caocci, Ester Orlandi, Daniele Cattaneo, Olga Mulas, Nicola Sgherza, Luigi Scaffidi, Massimiliano Bonifacio, Emilia Scalzulli, Mario Tiribelli, Fausto Castagnetti, Mulas O., Caocci G., Stagno F., Bonifacio M., Annunziata M., Luciano L., Orlandi E.M., Abruzzese E., Sgherza N., Martino B., Albano F., Galimberti S., Pregno P., Bocchia M., Castagnetti F., Tiribelli M., Binotto G., Gozzini A., Capodanno I., Fozza C., Luzi D., Efficace F., Simula M.P., Scaffidi L., De Gregorio F., Elena C., Trawinska M.M., Cattaneo D., Attolico I., Barate C., Pirillo F., Sicuranza A., Gugliotta G., Stella R., Scalzulli E., Iurlo A., Foa R., Breccia M., and La Nasa G.

Subjects
Male, Myeloid, Angiotensin-Converting Enzyme Inhibitors, Gastroenterology, Cohort Studies, Renin-Angiotensin System, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, 80 and over, Cumulative incidence, Chronic, Aged, 80 and over, Leukemia, Arterial occlusive events, Incidence, Ponatinib, Angiotensin Receptor Antagonist, Chronic myeloid leukemia, Myeloid leukemia, Hematology, General Medicine, Middle Aged, TKI, Dasatinib, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Combination, Hypertension, Drug Therapy, Combination, Female, Survival Analysi, medicine.drug, Human, Renin angiotensin system inhibitors, Adult, medicine.medical_specialty, Arterial occlusive event, Protein Kinase Inhibitor, 03 medical and health sciences, Angiotensin Receptor Antagonists, Drug Therapy, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Artery occlusion, Protein Kinase Inhibitors, Aged, business.industry, Risk Factor, Angiotensin-Converting Enzyme Inhibitor, Thrombosis, Renin angiotensin system inhibitor, Survival Analysis, Blood pressure, chemistry, Nilotinib, BCR-ABL Positive, Cohort Studie, business, 030215 immunology, Myelogenous
Abstract

Hypertension is a commonly reported comorbidity in patients diagnosed with chronic myeloid leukemia (CML), and its management represents a challenge in patients treated with 2nd- or 3rd-generation tyrosine kinase inhibitors (TKIs), considering their additional cardiovascular (CV) toxicity. The renin angiotensin system (RAS) contributes to hypertension genesis and plays an important role in atherosclerosis development, proliferation, and differentiation of myeloid hematopoietic cells. We analyzed a cohort of 192 patients with hypertension at CML diagnosis, who were treated with 2nd- or 3rd-generation TKIs, and evaluated the efficacy of RAS inhibitors (angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs)) in the prevention of arterial occlusive events (AOEs), as compared with other drug classes. The 5-year cumulative incidence of AOEs was 32.7 ± 4.2%. Patients with SCORE ≥ 5% (high-very-high) showed a significantly higher incidence of AOEs (33.7 ± 7.6% vs 13.6 ± 4.8%, p = 0.006). The AOE incidence was significantly lower in patients treated with RAS inhibitors (14.8 ± 4.2% vs 44 ± 1%, p < 0.001, HR = 0.283). The difference in the low and intermediate Sokal risk group was confirmed but not in the high-risk group, where a lower RAS expression has been reported. Our data suggest that RAS inhibitors may represent an optimal treatment in patients with hypertension and CML, treated with 2nd or 3rdG TKIs.

Published
2020

38. Favorable outcome of chronic myeloid leukemia co-expressing e13a2 and e14a2 transcripts, treated with nilotinib

Author

Sara Galimberti, Giovanni Caocci, Ester Orlandi, Mario Annunziata, Gabriele Gugliotta, Emilia Scalzulli, Alessandra Iurlo, Chiara Elena, Elisabetta Abruzzese, Daniele Cattaneo, Bruno Martino, Malgorzata Monika Trawinska, Giorgio La Nasa, Luigi Scaffidi, Francesca Pirillo, Anna Sicuranza, Luigiana Luciano, Fausto Castagnetti, Patrizia Pregno, Monica Bocchia, Nicola Sgherza, Francesco Albano, Robin Foà, Massimo Breccia, Fiorenza De Gregorio, Antonella Gozzini, Massimiliano Bonifacio, Claudia Baratè, Imma Attolico, Maria Pina Simula, Gianni Binotto, Claudio Fozza, Olga Mulas, Mulas O., Caocci G., Annunziata M., Martino B., Luciano L., Castagnetti F., Pregno P., Galimberti S., Albano F., Orlandi E.M., Sgherza N., Iurlo A., Bonifacio M., Binotto G., Gozzini A., Bocchia M., Abruzzese E., Fozza C., Simula M.P., De Gregorio F., Gugliotta G., Pirillo F., Barate C., Attolico I., Elena C., Cattaneo D., Scaffidi L., Sicuranza A., Trawinska M.M., Scalzulli E., Foa R., Breccia M., and La Nasa G.

Subjects
Oncology, Male, Cancer Research, Chromosomes, Human, Pair 22, bcr-abl, Messenger, Fusion Proteins, bcr-abl, Translocation, Genetic, 80 and over, Favorable outcome, RNA, Neoplasm, Chronic, Aged, 80 and over, Leukemia, Follow up studies, Myeloid leukemia, molecular response, Hematology, General Medicine, Middle Aged, Survival Rate, outcome, Female, Chromosomes, Human, Pair 9, medicine.drug, Human, Pair 9, Adult, medicine.medical_specialty, Disease free survival, transcript type, MEDLINE, Translocation, Disease-Free Survival, Chromosomes, Follow-Up Studie, Text mining, Genetic, chronic myeloid leukemia, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, RNA, Messenger, Survival rate, nilotinib, Aged, Follow-Up Studies, Pyrimidines, business.industry, chronic myeloid leukemia, nilotinib, transcript type, molecular response, outcome, Fusion Proteins, Nilotinib, Pyrimidine, RNA, Neoplasm, BCR-ABL Positive, Pair 22, business, Myelogenous
Abstract

No abstract available.

Published
2020

39. La valorizzazione dei carnevali storici della Campania come volano di sviluppo delle aree interne

Author

A. Acierno, I. Pistone, L. Scaffidi, Colletta T., De Toro P., Fusco Girard L., Acierno, A., Pistone, I., and Scaffidi, L.

Subjects
Aree interne, Carnevali storici, patrimonio immateriale
Abstract

Le pratiche e i riti popolari legati al carnevale costituiscono indubbiamente una componente significativa del patrimonio culturale immateriale dei territori. Rappresentano saperi antichi che si tramandano di generazione in generazione, coagulando le comunità intorno ad attività dal forte valore identitario rinnovandone il patto sociale e il senso di appartenenza ad uno specifico territorio. A questo valore immateriale se ne aggiunge anche uno più tangibile, legato all’indotto economico che spesso ruota attorno a tali manifestazioni, da quelle più articolate che richiamano migliaia di visitatori a quelle più modeste. Le sfilate dei carri, le manifestazioni canore e danzanti nonché le rappresentazioni teatrali determinano lo sviluppo di un’imprenditoria locale specializzata nella costruzione di carri e nella sartoria che si affianca agli altri settori coinvolti della ristorazione e della ricettività. I carnevali rappresentano pertanto una risorsa fondamentale in termini sociali, culturali ed economici e contribuiscono al marketing territoriale e all’immagine che si proietta all’esterno della comunità, rafforzando l’identità locale.

Published
2020

40. Low low-density lipoprotein (LDL), cholesterol and triglycerides plasma levels are associated with reduced risk of arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life. A Campus CML study

Author

Emilia Scalzulli, Fabio Efficace, Giovanni Caocci, Ester Orlandi, Sara Galimberti, Mario Tiribelli, Daniele Cattaneo, Elisabetta Abruzzese, Luigi Scaffidi, Olga Mulas, Immacolata Attolico, Debora Luzi, Massimiliano Bonifacio, Robin Foà, Chiara Elena, Rossella Stella, Fausto Castagnetti, Massimo Breccia, Maria Pina Simula, Claudia Baratè, Luigiana Luciano, Malgorzata Monika Trawinska, Francesco Albano, Fabio Stagno, Patrizia Pregno, Antonella Gozzini, Gianni Binotto, Gabriele Gugliotta, Giorgio La Nasa, Francesca Pirillo, Nicola Sgherza, Mario Annunziata, Alessandra Iurlo, Claudio Fozza, Isabella Capodanno, Fiorenza De Gregorio, Caocci G., Mulas O., Capodanno I., Abruzzese E., Iurlo A., Luciano L., Albano F., Annunziata M., Tiribelli M., Bonifacio M., Galimberti S., Castagnetti F., Sgherza N., Stagno F., Gozzini A., Orlandi E.M., Luzi D., Binotto G., Pregno P., Fozza C., Efficace F., Simula M.P., Trawinska M.M., Cattaneo D., De Gregorio F., Attolico I., Stella R., Scaffidi L., Barate C., Gugliotta G., Scalzulli E., Elena C., Pirillo F., Foa R., Breccia M., and Nasa G.L.

Subjects
Adult, Male, medicine.medical_specialty, Antineoplastic Agents, Arterial Occlusive Diseases, Gastroenterology, lcsh:RC254-282, chronic myeloid leukemia, TKI, ponatinib, arterial occlusive events, Article, chemistry.chemical_compound, Young Adult, Myeloproliferative disease, High-density lipoprotein, Low low-density lipoprotein, LDL, cholesterol, triglycerides, arterial occlusive events, chronic myeloid leukemia, ponatinib, CML, Campus, chronic myeloid leukemia, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Medicine, Humans, ponatinib, Artery occlusion, arterial occlusive events, Triglycerides, Aged, Aged, 80 and over, business.industry, Cholesterol, Ponatinib, Imidazoles, Myeloid leukemia, Hematology, Middle Aged, Protective Factors, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, TKI, Lipoproteins, LDL, Pyridazines, Leukemia, Oncology, chemistry, Risk factors, Low-density lipoprotein, Female, business, Dyslipidemia
Abstract

Not available.

Published
2020

41. Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: The NEXT-in-CML study

Author

Anna Serra, Antonio Percesepe, Gabriele Gugliotta, Caterina Musolino, Gianni Binotto, Elisabetta Abruzzese, Immacolata Attolico, Gianantonio Rosti, Mario Annunziata, Rosaria Sancetta, Mariella Girasoli, Fabrizio Pane, Maria Antonella Laginestra, Sara Galimberti, Alessandra Iurlo, Stefania Stella, Sabrina Coluzzi, Simona Sica, Monica Bocchia, Marzia Salvucci, Francesca Lunghi, Fabio Stagno, Nicola Orofino, Stefano Pileri, Federica Sorà, Santa Errichiello, Elisabetta Calistri, Paolo Vigneri, Fausto Castagnetti, Michele Baccarani, Luana Bavaro, Michele Cavo, Eros Di Bona, Francesco Di Raimondo, Claudia Baratè, Margherita Martelli, Simona Soverini, Antonella Russo Rossi, Francesco Albano, Mariella D'Adda, Fabio Ciceri, Flavio Mignone, Elena Tenti, Caterina De Benedittis, Giuseppe Saglio, Isabella Capodanno, Giovanni Martinelli, Massimiliano Bonifacio, Luigi Scaffidi, Soverini, S., Bavaro, L., de Benedittis, C., Martelli, M., Iurlo, A., Orofino, N., Sica, S., Sora, F., Lunghi, F., Ciceri, F., Galimberti, S., Barate, C., Bonifacio, M., Scaffidi, L., Castagnetti, F., Gugliotta, G., Albano, F., Rossi, A. V. R., Stagno, F., di Raimondo, F., D'Adda, M., di Bona, E., Abruzzese, E., Binotto, G., Sancetta, R., Salvucci, M., Capodanno, I., Girasoli, M., Coluzzi, S., Attolico, I., Musolino, C., Calistri, E., Annunziata, M., Bocchia, M., Stella, S., Serra, A., Errichiello, S., Saglio, G., Pane, F., Vigneri, P., Mignone, F., Laginestra, M. A., Pileri, S. A., Percesepe, A., Tenti, E., Rosti, G., Baccarani, M., Cavo, M., Martinelli, G., Soverini, Simona, Bavaro, Luana, De Benedittis, Caterina, Martelli, Margherita, Iurlo, Alessandra, Orofino, Nicola, Sica, Simona, Sora, Federica, Lunghi, Francesca, Ciceri, Fabio, Galimberti, Sara, Baratè, Claudia, Bonifacio, Massimiliano, Scaffidi, Luigi, Castagnetti, Fausto, Gugliotta, Gabriele, Albano, Francesco, Russo Rossi, Antonella Vita, Stagno, Fabio, Di Raimondo, Francesco, D'Adda, Mariella, Di Bona, Ero, Abruzzese, Elisabetta, Binotto, Gianni, Sancetta, Rosaria, Salvucci, Marzia, Capodanno, Isabella, Girasoli, Mariella, Coluzzi, Sabrina, Attolico, Immacolata, Musolino, Caterina, Calistri, Elisabetta, Annunziata, Mario, Bocchia, Monica, Stella, Stefania, Serra, Anna, Errichiello, Santa, Saglio, Giuseppe, Pane, Fabrizio, Vigneri, Paolo G, Mignone, Flavio, Laginestra, Maria Antonella, Pileri, Stefano A, Percesepe, Antonio, Tenti, Elena, Rosti, Gianantonio, Baccarani, Michele, Cavo, Michele, and Martinelli, Giovanni

Subjects
Oncology, Male, Mutation rate, bcr-abl, Drug Resistance, Fusion Proteins, bcr-abl, Gene mutation, medicine.disease_cause, Settore MED/01 - STATISTICA MEDICA, Biochemistry, Adult, Aged, Aged, 80 and over, Drug Resistance, Neoplasm, Female, High-Throughput Nucleotide Sequencing, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Middle Aged, Mutation, Mutation Rate, Prospective Studies, Protein Kinase Inhibitors, hemic and lymphatic diseases, 80 and over, cml mutation, BCR-ABL mutations, Chronic, Prospective cohort study, Sanger sequencing, Leukemia, Chronic myeloid leukemia, Myeloid leukemia, Hematology, TKI, NGS, symbols, Human, medicine.medical_specialty, Immunology, symbols.namesake, CML, TKIs, BCR-ABL1, Chronic myeloid leukemia,TKI,BCR-ABL mutations,Sanger Sequencing,NGS, Internal medicine, medicine, business.industry, Fusion Proteins, Cell Biology, medicine.disease, Clinical trial, Prospective Studie, Sanger Sequencing, Neoplasm, BCR-ABL Positive, business, Myelogenous
Abstract

In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n = 124) or warning (n = 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms.

Published
2020

42. Second primary malignancy in myelofibrosis patients treated with ruxolitinib

Author

Elena Maria Elli, Florian H. Heidel, Uros Markovic, Fabrizio Pane, Gianpietro Semenzato, Daniela Bartoletti, Francesca Palandri, Giulia Benevolo, Mauro Krampera, Malgorzata Monika Trawinska, Micaela Bergamaschi, Mario Tiribelli, Giovanni Caocci, Lucia Catani, Elisabetta Abruzzese, Massimo Breccia, Rossella Stella, Antonio Cuneo, Fabio D'Amore, Alessandro Isidori, Costanza Bosi, Monica Crugnola, Lisa Gandolfi, Domenico Russo, Alessandra Iurlo, Nicola Polverelli, Roberto M. Lemoli, Michele Cavo, Gianni Binotto, Roberto Latagliata, Francesco Cavazzini, Bruno Martino, Daniele Cattaneo, Nicola Vianelli, Novella Pugliese, Luigi Scaffidi, Massimiliano Bonifacio, Mariella D'Adda, Alessia Tieghi, Giuseppe Auteri, Giuseppe A. Palumbo, Polverelli N., Elli E.M., Abruzzese E., Palumbo G.A., Benevolo G., Tiribelli M., Bonifacio M., Tieghi A., Caocci G., D'Adda M., Bergamaschi M., Binotto G., Heidel F.H., Cavazzini F., Crugnola M., Pugliese N., Bosi C., Isidori A., Bartoletti D., Auteri G., Latagliata R., Gandolfi L., Martino B., Scaffidi L., Cattaneo D., D'Amore F., Trawinska M.M., Stella R., Markovic U., Catani L., Pane F., Cuneo A., Krampera M., Semenzato G., Lemoli R.M., Vianelli N., Breccia M., Russo D., Cavo M., Iurlo A., and Palandri F.

Subjects
Male, Ruxolitinib, Skin Neoplasms, Lymphoma, ruxolitinib, Aggressive lymphoma, Gastroenterology, Hydroxycarbamide, 0302 clinical medicine, myelofibrosi, Risk Factors, Neoplasms, 80 and over, Aged, 80 and over, Thrombocytosis, Incidence (epidemiology), Incidence, Hazard ratio, Neoplasms, Second Primary, Hematology, Arteries, Middle Aged, Second Primary, JAK inhibitor, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Context (language use), myelofibrosis, JAK inhibitors, second cancer, toxicity, NO, 03 medical and health sciences, Internal medicine, Nitriles, medicine, Humans, Janus Kinase Inhibitors, Myelofibrosis, Aged, Retrospective Studies, business.industry, Thrombosis, medicine.disease, Case-Control Studies, Follow-Up Studies, Multivariate Analysis, Primary Myelofibrosis, Pyrazoles, Pyrimidines, business, 030215 immunology
Abstract

Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22–4·60, P=0·01] and thrombocytosis>400×109/l at RUX start (HR:1·98, 95%CI: 1·10–4·60, P=0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24–7·92, P=0·02) and duration of hydroxycarbamide and RUX therapy>5years (HR: 3·20, 95%CI: 1·17–8·75, P=0·02 and HR: 2·93, 95%CI: 1·39–6·17, P=0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11–5·25, P=0·03), platelet>400×109/l (HR: 3·30, 95%CI: 1·67–6·50, P=0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48–8·14, P=0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.

Published
2020

43. Long-term mortality rate for cardiovascular disease in 656 chronic myeloid leukaemia patients treated with second- and third-generation tyrosine kinase inhibitors

Author

Gabriele Gugliotta, Francesca Pirillo, Bruno Martino, Fausto Castagnetti, Chiara Elena, Antonella Gozzini, Giorgio La Nasa, Massimiliano Bonifacio, Claudia Baratè, Gianni Binotto, Robin Foà, Daniele Cattaneo, Nicola Sgherza, Alessandra Iurlo, Monica Bocchia, Elisabetta Abruzzese, Mario Annunziata, Claudio Fozza, Fiorenza De Gregorio, Matteo Molica, Luigi Scaffidi, Sara Galimberti, Olga Mulas, Giovanni Caocci, Imma Attolico, Ester Orlandi, Maria Pina Simula, Luigiana Luciano, Massimo Breccia, Francesco Albano, Fabio Stagno, Patrizia Pregno, Anna Sicuranza, Malgorzata Monika Trawinska, Caocci G., Mulas O., Annunziata M., Luciano L., Abruzzese E., Bonifacio M., Orlandi E.M., Albano F., Galimberti S., Iurlo A., Pregno P., Sgherza N., Martino B., Binotto G., Castagnetti F., Gozzini A., Bocchia M., Fozza C., Stagno F., Simula M.P., De Gregorio F., Trawinska M.M., Scaffidi L., Elena C., Attolico I., Barate C., Cattaneo D., Pirillo F., Gugliotta G., Sicuranza A., Molica M., La Nasa G., Foa R., and Breccia M.

Subjects
Male, Chronic myeloid leuk, Dasatinib, emia, Long Term Adverse Effects, Long Term Adverse Effect, 030204 cardiovascular system & hematology, Antineoplastic Agent, chemistry.chemical_compound, 0302 clinical medicine, Cardiovascular Disease, Cardiovascular toxicity, Ischemic heart disease, TKI, Aged, Antineoplastic Agents, Female, Humans, Italy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Life Expectancy, Mortality, Protein Kinase Inhibitors, Risk Adjustment, Aniline Compounds, Cardiotoxicity, Cardiovascular Diseases, Imidazoles, Nitriles, Pyridazines, Pyrimidines, Quinolines, 030212 general & internal medicine, Chronic, education.field_of_study, Leukemia, Mortality rate, Ponatinib, Aniline Compound, a, Pyridazine, Cardiology and Cardiovascular Medicine, Nitrile, Bosutinib, Human, medicine.drug, medicine.medical_specialty, Population, Protein Kinase Inhibitor, 03 medical and health sciences, Internal medicine, medicine, education, Imidazole, Survival rate, business.industry, Standardized mortality ratio, Pyrimidine, Nilotinib, chemistry, BCR-ABL Positive, business, Myelogenous
Abstract

Background Limited information is available regarding the rate of long-term cardiovascular (CV) mortality in chronic myeloid leukaemia (CML) patients treated with second- and third-generation tyrosine kinase inhibitors (2ndG/3rdG TKIs) in the real-life practice. Methods We identified 656 consecutive CML patients treated with nilotinib, dasatinib, bosutinib and ponatinib. Results The 15-year CV-mortality free survival was 93 ± 2.8%. Age ≥65 years (p = 0.005) and a positive history of CV disease (p = 0.04) were significantly associated with a lower CV-mortality free survival. CV disease accounted for 16.5% and 5% of potential years of life lost (PYLL) in male and female patients, respectively. The standard mortality ratio (SMR) following ischemic heart disease (IHD) was 3.9 in males and 3.8 in female patients, meaning an excess of IHD deaths observed, in comparison with the population of control. Conclusion. Prevention strategies based on CV risk factors, in particular in those patients with a previous history of CV disease, should be considered.

Published
2019

44. Recurrent arterial occlusive events in patients with chronic myeloid leukemia treated with second- and third-generation tyrosine kinase inhibitors and role of secondary prevention

Author

Claudio Fozza, Giovanni Caocci, Ester Orlandi, Massimiliano Bonifacio, Chiara Elena, Bruno Martino, Daniele Cattaneo, Mario Annunziata, Luigi Scaffidi, Antonella Gozzini, Sara Galimberti, Olga Mulas, Fabio Stagno, Gianni Binotto, Patrizia Pregno, Giorgio La Nasa, Robin Foà, Fausto Castagnetti, Alessandra Iurlo, Malgorzata Monika Trawinska, Massimo Breccia, Emilia Scalzulli, Luigiana Luciano, Francesco Albano, Claudia Baratè, Elisabetta Abruzzese, Caocci G., Mulas O., Bonifacio M., Abruzzese E., Galimberti S., Orlandi E.M., Iurlo A., Annunziata M., Luciano L., Castagnetti F., Gozzini A., Stagno F., Binotto G., Pregno P., Albano F., Martino B., Fozza C., Scaffidi L., Trawinska M.M., Barate C., Elena C., Cattaneo D., Scalzulli E., La Nasa G., Foa R., and Breccia M.

Subjects
Oncology, Male, Time Factors, 030204 cardiovascular system & hematology, chemistry.chemical_compound, 0302 clinical medicine, Recurrent arterial occlusive event, Recurrence, Risk Factors, 80 and over, Secondary Prevention, Medicine, Cumulative incidence, 030212 general & internal medicine, Chronic, Aged, 80 and over, Chronic myeloid leukemia, Secondary prophylaxis, Leukemia, Incidence (epidemiology), Incidence, Ponatinib, Myeloid leukemia, Middle Aged, Aged, Anticoagulants, Arterial Occlusive Diseases, Female, Follow-Up Studies, Humans, Italy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Platelet Aggregation Inhibitors, Protein Kinase Inhibitors, Treatment Outcome, Dasatinib, Platelet aggregation inhibitor, Cardiology and Cardiovascular Medicine, Bosutinib, medicine.drug, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, business.industry, chemistry, Nilotinib, BCR-ABL Positive, business, Myelogenous
Abstract

Background Risk of death is particularly high in patients with a previous history of arterial occlusive events (AOEs) and the probability for a recurrent event is around 20%. Little is known about recurrent AOE and the role of secondary prevention in patients with Chronic Myeloid Leukemia (CML) with previous AOE, treated with second- and third-generation tyrosine kinase inhibitors (2ndG/3rdG TKIs), nilotinib, dasatinib, bosutinib and ponatinib. Methods We identified a real-life cohort of 57 consecutive adult CML patients treated with 2ndG/3rdG TKI. All patients had a previous history of AOE. Ongoing use of secondary prevention of AOE (including antiplatelet agents, anticoagulant therapy, and statins) before starting a 2ndG/3rdG TKI was recorded, as well as CV risk factors. Results The 60-month cumulative incidence rate of recurrent AOEs was 47.8 ± 10.9%. Despite a history of AOE, 10 patients (16%) were not receiving secondary preventative measures. Patients treated with nilotinib and ponatinib showed a higher incidence of recurrent AOEs (76.7 ± 14.3% and 64 ± 20.1%, respectively) than those treated with dasatinib and bosutinib (44 ± 24.2% and 30.5 ± 15.5%, respectively) (p = 0.01). Only treatment with a 2ndG/3rdG TKI given as second or subsequent line therapy showed a significant association with an increased incidence of recurrent AOE (p = 0.039). Overall, 17 recurrent AOEs were observed; 3 CV-related deaths were reported. Conclusion CML patients with a previous history of AOE treated with 2ndG/3rdG TKI represent a particular patient population with a higher probability of experiencing a recurrent AOE; individualized treatment is needed to optimize secondary prevention.

Published
2019

45. Arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life practice are predicted by the Systematic Coronary Risk Evaluation (SCORE) chart

Author

Giovanni Caocci, Massimo Breccia, Ester Orlandi, Antonella Gozzini, Robin Foà, Luigiana Luciano, Nicola Sgherza, Francesco Albano, Sara Galimberti, Massimiliano Bonifacio, Elisabetta Abruzzese, Gabriele Gugliotta, Olga Mulas, Daniele Cattaneo, Gianni Binotto, Chiara Elena, Luigi Scaffidi, Claudia Baratè, Fabio Stagno, Patrizia Pregno, Immacolata Attolico, Fiorenza De Gregorio, Emilia Scalzulli, Fausto Castagnetti, Mario Annunziata, Giorgio La Nasa, Alessandra Iurlo, Francesca Pirillo, Malgorzata Monika Trawinska, Claudio Fozza, Caocci G., Mulas O., Abruzzese E., Luciano L., Iurlo A., Attolico I., Castagnetti F., Galimberti S., Sgherza N., Bonifacio M., Annunziata M., Gozzini A., Orlandi E.M., Stagno F., Binotto G., Pregno P., Fozza C., Trawinska M.M., De Gregorio F., Cattaneo D., Albano F., Gugliotta G., Barate C., Scaffidi L., Elena C., Pirillo F., Scalzulli E., La Nasa G., Foa R., and Breccia M.

Subjects
Male, Cancer Research, Decision Support Systems, Medical Oncology, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Retrospective Studie, Original Research Articles, Epidemiology, 80 and over, Medicine, Cumulative incidence, ponatinib, Original Research Article, arterial occlusive event, Chronic, Aged, 80 and over, Aspirin, Leukemia, Incidence (epidemiology), Incidence, Ponatinib, Imidazoles, Hematology, General Medicine, Middle Aged, Pyridazines, Treatment Outcome, Oncology, Italy, 030220 oncology & carcinogenesis, Hypertension, Female, prophylaxis, Pyridazine, medicine.drug, Human, Adult, medicine.medical_specialty, Chronic myeloid leukemia, Cardiology, 03 medical and health sciences, Clinical, Young Adult, chronic myeloid leukemia, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Humans, Risk factor, Imidazole, Retrospective Studies, Aged, business.industry, prophylaxi, Risk Factor, Coronary Occlusion, Decision Support Systems, Clinical, Retrospective cohort study, Blood pressure, chemistry, BCR-ABL Positive, business, 030215 immunology, Myelogenous
Abstract

Arterial occlusive events (AOEs) represent emerging complications in chronic myeloid leukemia (CML) patients treated with ponatinib. We identified 85 consecutive CML adult patients who were treated with ponatinib in 17 Italian centers. Patients were stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 60-month cumulative incidence rate of AOEs excluding hypertension was 25.7%. Hypertension was reported in 14.1% of patients. The median time of exposure to ponatinib was 28months (range, 3-69months). Patients with a high to very high SCORE risk showed a significantly higher incidence rate of AOEs (74.3% vs 15.2%, P&nbsp

Published
2019

46. Differences in presenting features, outcome and prognostic models in patients with primary myelofibrosis and post-polycythemia vera and/or post-essential thrombocythemia myelofibrosis treated with ruxolitinib. New perspective of the MYSEC-PM in a large multicenter study

Author

Costanza Bosi, Franco Aversa, Elisabetta Abruzzese, Nicola Vianelli, Giulia Benevolo, G. Semenzato, Bruno Martino, Daniele Cattaneo, Adalberto Ibatici, Nicola Polverelli, Daniela Bartoletti, Nicola Sgherza, Massimiliano Bonifacio, Roberto Latagliata, Francesca Palandri, Francesco Di Raimondo, Francesco Cavazzini, Micaela Bergamaschi, Michele Cavo, Massimo Breccia, Mariella D'Adda, Alessandra Iurlo, Alessandro Isidori, Maria Letizia Bacchi Reggiani, Giuseppe A. Palumbo, Luigi Scaffidi, Alessia Tieghi, Gianni Binotto, Antonio Cuneo, Monica Crugnola, Francesco Soci, Roberto M. Lemoli, Mario Tiribelli, Lucia Catani, Giuseppe Auteri, Malgorzata Monika Trawinska, Florian H. Heidel, Domenico Penna, Domenico Russo, and Palandri F, Palumbo GA, Iurlo A, Polverelli N, Benevolo G, Breccia M, Abruzzese E, Tiribelli M, Bonifacio M, Tieghi A, Isidori A, Martino B, Sgherza N, D'Adda M, Bergamaschi M, Crugnola M, Cavazzini F, Bosi C, Binotto G, Auteri G, Latagliata R, Ibatici A, Scaffidi L, Penna D, Cattaneo D, Soci F, Trawinska M, Russo D, Cuneo A, Semenzato G, Di Raimondo F, Aversa F, Lemoli RM, Heidel F, Reggiani MLB, Bartoletti D, Cavo M, Catani L, Vianelli N.

Subjects
Ruxolitinib, medicine.medical_specialty, Anemia, Socio-culturale, Myelofibrosis, Gastroenterology, MYSEC-PM, Efficacy, 03 medical and health sciences, Essential, 0302 clinical medicine, Polycythemia vera, Internal medicine, Nitriles, Risk scores, Humans, Medicine, Thrombocythemia, Polycythemia Vera, Survival rate, Janus Kinases, business.industry, Essential thrombocythemia, IPSS, Myelofibrosi, Hematology, Prognosis, medicine.disease, Primary Myelofibrosis, Pyrazoles, Survival Rate, Thrombocythemia, Essential, Pyrimidines, International Prognostic Scoring System, 030220 oncology & carcinogenesis, Risk score, business, IPSS, MYSEC-PM, Myelofibrosis, Risk scores, Ruxolitinib, 030215 immunology, medicine.drug
Abstract

Recently, the myelofibrosis secondary to PV and ET prognostic model (MYSEC-PM) was introduced to assess prognosis in myelofibrosis (MF) secondary to polycythemia vera and essential thrombocythemia (post-PV and post-ET MF), replacing the International Prognostic Scoring System (IPSS) and/or Dynamic IPSS (DIPSS) that was applied for primary MF (PMF). In a cohort of 421 ruxolitinib (RUX)-treated patients (post-PV and post-ET MF: 44.2%), we evaluated the following: (1) disease phenotype, responses, and toxicity to RUX; and (2) performance of the MYSEC-PM in post-PV or post-ET ME. While the IPSS failed to correctly stratify post-PV or post-ET MF patients at diagnosis, the MYSEC-PM identified 4 risk categories projected at significantly different survival probability (P < .001). Additionally, the MYSEC-PM maintained a prognostic value in post-PV and post-ET MF also when used over time, at RUX start. Notably, the MYSEC-PM reclassified 41.8% and 13.6% of patients into a lower and higher risk category, respectively. Finally, patients at intermediate-1 risk had significantly higher spleen responses and lower hematological toxicities compared to higher risk patients. Compared to PMF, post-PV and post-ET MF presented a more hyperproliferative disease, with higher leukocyte and/or platelet count and hemoglobin levels both at diagnosis and at RUX start. Despite comparable response rates, post-PV and post-ET MF had lower rate of RUX-induced anemia and thrombocytopenia at 3 and 6 months. The study validates MYSEC-PM in post-PV and post-ET MF prognostication. Post-PV or post-ET MF represents a separate entity compared to PMF in terms of clinical manifestations and toxicity to RUX. (C) 2018 Elsevier Inc. All rights reserved.

Published
2018

47. Incidence of blast phase in myelofibrosis patients according to anemia severity at ruxolitinib start and during therapy.

Author

Palandri F, Palumbo GA, Benevolo G, Iurlo A, Elli EM, Abruzzese E, Polverelli N, Tiribelli M, Auteri G, Tieghi A, Caocci G, Binotto G, Cavazzini F, Branzanti F, Beggiato E, Miglino M, Bosi C, Crugnola M, Bocchia M, Martino B, Pugliese N, Scaffidi L, Venturi M, Duminuco A, Isidori A, Cattaneo D, Krampera M, Pane F, Cilloni D, Semenzato G, Lemoli RM, Cuneo A, Trawinska MM, Vianelli N, Cavo M, Bonifacio M, and Breccia M

Subjects
Male, Humans, Female, Blast Crisis, Treatment Outcome, Incidence, Retrospective Studies, Nitriles, Hemoglobins, Primary Myelofibrosis drug therapy, Anemia chemically induced, Anemia epidemiology, Pyrazoles, Pyrimidines
Abstract

Background: Anemia is frequently present in patients with myelofibrosis (MF), and it may be exacerbated by treatment with the JAK2-inhibitor ruxolitinib (RUX). Recently, a relevant blast phase (BP) incidence has been reported in anemic MF patients unexposed to RUX., Methods: The authors investigated the incidence of BP in 886 RUX-treated MF patients, included in the "RUX-MF" retrospective study., Results: The BP incidence rate ratio (IRR) was 3.74 per 100 patient-years (3.74 %p-y). At therapy start, Common Terminology Criteria for Adverse Events grade 3-4 anemia (hemoglobin [Hb] <8 g/dL) and severe sex/severity-adjusted anemia (Hb <8/<9 g/dL in women/men) were present in 22.5% and 25% patients, respectively. IRR of BP was 2.34 in patients with no baseline anemia and reached respectively 4.22, 4.89, and 4.93 %p-y in patients with grade 1, 2, and 3-4 anemia. Considering the sex/severity-adjusted Hb thresholds, IRR of BP was 2.85, 4.97, and 4.89 %p-y in patients with mild/no anemia, moderate, and severe anemia. Transfusion-dependent patients had the highest IRR (5.03 %p-y). Progression-free survival at 5 years was 70%, 52%, 43%, and 27% in patients with no, grade 1, 2, and 3-4 anemia, respectively (p < .001). At 6 months, 260 of 289 patients with no baseline anemia were receiving ruxolitinib, and 9.2% had developed a grade 3-4 anemia. By 6-month landmark analysis, BP-free survival was significantly worse in patients acquiring grade 3-4 anemia (69.3% vs. 88.1% at 5 years, p < .001)., Conclusions: This study highlights that anemia correlates with an increased risk of evolution into BP, both when present at baseline and when acquired during RUX monotherapy. Innovative anemia therapies and disease-modifying agents are warranted in these patients., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Published
2024
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48. A successful treatment-free remission is achievable also by chronic myeloid leukemia patients lacking optimal requirements.

Author

Bonifacio M, Scaffidi L, Miggiano MC, Facchinelli D, Tosoni L, Pezone S, Griguolo D, Ciotti G, Danini M, Bernardelli A, Bresciani R, Cavraro M, Crosera L, De March E, Dell'Eva M, Dorotea L, Frison L, Furlani L, Gianesello I, Lovato E, Marchetti E, Morelli G, Mullai R, Pizzano U, Zoletto S, Fanin R, Krampera M, Trentin L, Calistri E, Carli G, Binotto G, and Tiribelli M

Subjects
Humans, Chronic Disease, Remission Induction, Treatment Outcome, Protein Kinase Inhibitors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid
Published
2024
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49. The new Systematic Coronary Risk Evaluation (SCORE2 and SCORE2-OP) estimates the risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib or ponatinib.

Author

Mulas O, Abruzzese E, Luciano L, Iurlo A, Attolico I, Castagnetti F, Galimberti S, Bonifacio M, Annunziata M, Gozzini A, Orlandi EM, Stagno F, Binotto G, Pregno P, Fozza C, Loi M, Trawinska MM, De Gregorio F, Cattaneo D, Albano F, Iezza M, Baratè C, Scaffidi L, Elena C, Giai V, Scalzulli E, Breccia M, La Nasa G, and Caocci G

Subjects
Adult, Humans, Aged, Aged, 80 and over, Imidazoles adverse effects, Pyrimidines therapeutic use, Protein Kinase Inhibitors adverse effects, Cardiovascular Diseases chemically induced, Cardiovascular Diseases epidemiology, Cardiovascular Diseases drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive chemically induced, Pyridazines
Abstract

Patients with chronic myeloid leukemia (CML) treated with nilotinib or ponatinib may experience arterial occlusive events (AOEs). It is currently recommended to thoroughly assess cardiovascular risk factors before treating CML. We identified 455 consecutive CML adult patients, 335 treated with nilotinib and 120 with ponatinib; 380 patients without previous cardiovascular diseases or diabetes were stratified according to the Systematic Coronary Risk Evaluation (SCORE2) and SCORE2-Older Persons (SCORE2-OP). This updated algorithm from the European Society of Cardiology (ESC) estimates a 10-year risk of fatal and non-fatal cardiovascular diseases. It is based on sex, age, smoking habits, systolic blood pressure, non-high-density lipoprotein cholesterol, and European geographical region of cardiovascular risk. The SCORE2/SCORE2-OP algorithm translated more patients (50.2%) to the high-very high cardiovascular risk category than the previous SCORE (25.3%). Patients with a high to very high SCORE2/SCORE2-OP risk showed a significantly higher incidence rate of AOEs (69.2% vs. 46.5%, p < 0.001). The older SCORE was less specific in estimating AOEs in patients classified as low-intermediate risk (69.8 vs. 54.2%). In multivariate analysis, no associations were found between AOEs and gender, age, and type or dose of tyrosine kinase inhibitor. Only the SCORE2/SCORE2-OP risk was confirmed as a significant predictive factor (p = 0.028; hazard ratio = 2.2; 95% confidence interval = 1.1-4.5). Patients with AOEs required, in most cases, imaging diagnostic tests, additional drugs, and sometimes invasive procedures, increasing access to visits and hospital management. This real-life study suggested that the SCORE2 and SCORE2-OP charts could help identify cardiovascular fragility in CML patients providing them with more attention and a proper TKI selection., (© 2023. The Author(s).)

Published
2024
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50. Ropeginterferon phase 2 randomized study in low-risk polycythemia vera: 5-year drug survival and efficacy outcomes.

Author

Barbui T, Carobbio A, De Stefano V, Alvarez-Larran A, Ghirardi A, Carioli G, Fenili F, Rossi E, Ciceri F, Bonifacio M, Iurlo A, Palandri F, Benevolo G, Pane F, Ricco A, Carli G, Caramella M, Rapezzi D, Musolino C, Siragusa S, Rumi E, Patriarca A, Cascavilla N, Mora B, Cacciola E, Calabresi L, Loscocco GG, Guglielmelli P, Gesullo F, Betti S, Ramundo F, Lunghi F, Scaffidi L, Bucelli C, Cattaneo D, Vianelli N, Bellini M, Finazzi MC, Tognoni G, Rambaldi A, and Vannucchi AM

Subjects
Humans, Hematocrit, Risk Factors, Phlebotomy, Bloodletting, Polycythemia Vera drug therapy, Polycythemia Vera diagnosis
Abstract

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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