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1. Antibody Response to the SARS-CoV-2 Vaccine and COVID-19 Vulnerability during the Omicron Pandemic in Patients with CLL: Two-Year Follow-Up of a Multicenter Study

Author

Mauro, Francesca R., primary, Giannarelli, Diana, additional, Galluzzo, Clementina M., additional, Visentin, Andrea, additional, Frustaci, Anna M., additional, Sportoletti, Paolo, additional, Vitale, Candida, additional, Reda, Gianluigi, additional, Gentile, Massimo, additional, Levato, Luciano, additional, Murru, Roberta, additional, Armiento, Daniele, additional, Molinari, Maria C., additional, Proietti, Giulia, additional, Pepe, Sara, additional, De Falco, Filomena, additional, Mattiello, Veronica, additional, Barabino, Luca, additional, Amici, Roberta, additional, Coscia, Marta, additional, Tedeschi, Alessandra, additional, Girmenia, Corrado, additional, Trentin, Livio, additional, and Baroncelli, Silvia, additional

Published
2023
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2. EFFICACY AND SAFETY OF MOLTO, A MULTICENTER, OPEN LABEL, PHASE II CLINICAL TRIAL EVALUATING VENETOCLAX, ATEZOLIZUMAB AND OBINUTUZUMAB COMBINATION IN RICHTER SYNDROME

Author

Frustaci, A, Montillo, M, Rossi, D, Zinzani, P, Motta, M, Gaidano, G, Quaresmini, G, Scarfò, L, Pietrasanta, D, Coscia, M, Deodato, M, Zamprogna, G, Cairoli, R, Stüssi, G, Zucca, E, Pileri, S, Zenz, T, Tedeschi, A, Frustaci A. M., Montillo M., Rossi D., Zinzani P. L., Motta M., Gaidano G., Quaresmini G., Scarfò L., Pietrasanta D., Coscia M., Deodato M., Zamprogna G., Cairoli R., Stüssi G., Zucca E., Pileri S., Zenz T., Tedeschi A., Frustaci, A, Montillo, M, Rossi, D, Zinzani, P, Motta, M, Gaidano, G, Quaresmini, G, Scarfò, L, Pietrasanta, D, Coscia, M, Deodato, M, Zamprogna, G, Cairoli, R, Stüssi, G, Zucca, E, Pileri, S, Zenz, T, Tedeschi, A, Frustaci A. M., Montillo M., Rossi D., Zinzani P. L., Motta M., Gaidano G., Quaresmini G., Scarfò L., Pietrasanta D., Coscia M., Deodato M., Zamprogna G., Cairoli R., Stüssi G., Zucca E., Pileri S., Zenz T., and Tedeschi A.

Published
2023

3. Report of consensus panel 5 from the 11th international workshop on Waldenstrom's macroglobulinemia on COVID-19 prophylaxis and management

Author

Terpos, Evangelos, Branagan, A. R., García-Sanz, Ramón, Trotman, Judith, Greenberger, L. M., Stephens, D. M., Morel, P., Kimby, E., Frustaci, A. M., Hatjiharissi, E., San-Miguel, Jesús, Dimopoulos, Meletios A., Treon, Steven P., Leblond, Véronique, Terpos, Evangelos, Branagan, A. R., García-Sanz, Ramón, Trotman, Judith, Greenberger, L. M., Stephens, D. M., Morel, P., Kimby, E., Frustaci, A. M., Hatjiharissi, E., San-Miguel, Jesús, Dimopoulos, Meletios A., Treon, Steven P., and Leblond, Véronique

Abstract

Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.

Published
2023

4. Tixagevimab/Cilgavimab Pre-exposure Prophylaxis in Patients with Lymphoproliferative Disorders on BTKi

Author

Zamprogna, G, Frustaci, A, Travi, G, Borella, C, Reda, G, Motta, M, Deodato, M, Bossi, E, Mattiello, V, Ferrari, M, Cotilli, G, Gambacorti-Passerini, C, Cairoli, R, Puoti, M, Tedeschi, A, Zamprogna G., Frustaci A. M., Travi G., Borella C., Reda G., Motta M., Deodato M., Bossi E., Mattiello V., Ferrari M. B., Cotilli G., Gambacorti-Passerini C., Cairoli R., Puoti M., Tedeschi A., Zamprogna, G, Frustaci, A, Travi, G, Borella, C, Reda, G, Motta, M, Deodato, M, Bossi, E, Mattiello, V, Ferrari, M, Cotilli, G, Gambacorti-Passerini, C, Cairoli, R, Puoti, M, Tedeschi, A, Zamprogna G., Frustaci A. M., Travi G., Borella C., Reda G., Motta M., Deodato M., Bossi E., Mattiello V., Ferrari M. B., Cotilli G., Gambacorti-Passerini C., Cairoli R., Puoti M., and Tedeschi A.

Published
2023

5. Ibrutinib in patients over 80 years old with CLL: a multicenter Italian cohort

Author

Reda, G., Mattiello, V., Frustaci, A. M., Visentin, A., Mauro, F. R., Innocenti, Idanna, Gentile, M., Giannarelli, Diana, Noto, A., Cassin, R., Neri, A., Laurenti, Luca, Tedeschi, Alessandra, Innocenti I., Giannarelli D., Laurenti L. (ORCID:0000-0002-8327-1396), Tedeschi A., Reda, G., Mattiello, V., Frustaci, A. M., Visentin, A., Mauro, F. R., Innocenti, Idanna, Gentile, M., Giannarelli, Diana, Noto, A., Cassin, R., Neri, A., Laurenti, Luca, Tedeschi, Alessandra, Innocenti I., Giannarelli D., Laurenti L. (ORCID:0000-0002-8327-1396), and Tedeschi A.

Abstract

NA

Published
2023

6. Long-term benefit of IGHV mutated patients in a real-life multicenter cohort of FCR-treated chronic lymphocytic leukemia

Author

Moia, R., Dondolin, R., De Propris, M. S., Talotta, D., Mouhssine, S., Perutelli, F., Reda, G., Mattiello, V., Rigolin, G. M., Motta, M., Olivieri, J., Fanin, R., Perbellini, O., Ferrarini, I., Mauro, F. R., Del Giudice, I., Laurenti, Luca, Tomasso, Annamaria, Gentile, M., Frustaci, A. M., Tedeschi, Alessandra, Gozzetti, A., Stelitano, C., Visco, C., Moreno, C., Forconi, F., Marasca, R., Coscia, M., Rossi, Dario, Foa, Robin, Gaidano, G., Laurenti L. (ORCID:0000-0002-8327-1396), Tomasso A., Tedeschi A., Rossi D., Foa R., Moia, R., Dondolin, R., De Propris, M. S., Talotta, D., Mouhssine, S., Perutelli, F., Reda, G., Mattiello, V., Rigolin, G. M., Motta, M., Olivieri, J., Fanin, R., Perbellini, O., Ferrarini, I., Mauro, F. R., Del Giudice, I., Laurenti, Luca, Tomasso, Annamaria, Gentile, M., Frustaci, A. M., Tedeschi, Alessandra, Gozzetti, A., Stelitano, C., Visco, C., Moreno, C., Forconi, F., Marasca, R., Coscia, M., Rossi, Dario, Foa, Robin, Gaidano, G., Laurenti L. (ORCID:0000-0002-8327-1396), Tomasso A., Tedeschi A., Rossi D., and Foa R.

Abstract

NA

Published
2022

7. Ibrutinib dose intensity in high-risk chronic lymphocytic leukemia

Author

Forestieri, G., Terzi di Bergamo, L., Deodato, M., Frustaci, A. M., Moia, R., Deambrogi, C., Rasi, S., Autore, Francesco, Merli, Maria Clara, Mattarucchi, R., Fahrni, G., Scarfo', L., Gussetti, D., Bulian, P., Zanatta, A., Spina, V., Bruscaggin, A., Pini, K., Piffaretti, D., Pirosa, M. C., Salehi, M., Marques de Almeida, J., Passweg, J., Cavalli, F., Zucca, E., Gerber, B., Stussi, G., Gattei, V., Ghia, P., Gregor, M., Passamonti, F., Laurenti, Luca, Gaidano, G., Tedeschi, Alessandra, Rossi, Dario, Condoluci, A., Autore F., Merli M., Laurenti L. (ORCID:0000-0002-8327-1396), Tedeschi A., Rossi D., Forestieri, G., Terzi di Bergamo, L., Deodato, M., Frustaci, A. M., Moia, R., Deambrogi, C., Rasi, S., Autore, Francesco, Merli, Maria Clara, Mattarucchi, R., Fahrni, G., Scarfo', L., Gussetti, D., Bulian, P., Zanatta, A., Spina, V., Bruscaggin, A., Pini, K., Piffaretti, D., Pirosa, M. C., Salehi, M., Marques de Almeida, J., Passweg, J., Cavalli, F., Zucca, E., Gerber, B., Stussi, G., Gattei, V., Ghia, P., Gregor, M., Passamonti, F., Laurenti, Luca, Gaidano, G., Tedeschi, Alessandra, Rossi, Dario, Condoluci, A., Autore F., Merli M., Laurenti L. (ORCID:0000-0002-8327-1396), Tedeschi A., and Rossi D.

Abstract

NA

Published
2022

8. Should Patients with Waldenström Macroglobulinemia Receive a BTK Inhibitor as Frontline Therapy?

Author

Deodato, M, Frustaci, A, Zamprogna, G, Cotilli, G, Cairoli, R, Tedeschi, A, Deodato M., Frustaci A. M., Zamprogna G., Cotilli G., Cairoli R., Tedeschi A., Deodato, M, Frustaci, A, Zamprogna, G, Cotilli, G, Cairoli, R, Tedeschi, A, Deodato M., Frustaci A. M., Zamprogna G., Cotilli G., Cairoli R., and Tedeschi A.

Abstract

Waldenström Macroglobulinemia (WM) is a rare indolent lymphoma with heterogeneous clinical presentation. As there are no randomised trials suggesting the best treatment option in treatment-naive patients, guidelines suggest either rituximab-combining regimens or BTK-inhibitors (BTKi) as feasible alternatives. Several factors play in the decision-making process: patients’ age and fitness, disease characteristics and genotype. Chemoimmunotherapy (CIT) represents a fixed-duration, less expensive and effective option, able to achieve prolonged time-to-next treatment even in patients with unfavourable genotypes. Immunosuppression and treatment-related second cancers may represent serious concerns. Proteasome-inhibitor-based regimens are effective with rapid disease control, although bortezomib-related neuropathy discourages the choice of these agents and treatment schedules may not be easily manageable in the elderly. BTKi have demonstrated high rates of response and prolonged survival together with the convenience of an oral administration and limited cytopenias. However, outcomes are impacted by genotype and some concerns remain, in particular the continuous drug exposure that may result in extra-haematological complications and drug resistance. Although next-generation BTKi have improved treatment tolerance, the question whether BTKi should be offered as frontline therapy to every patient is still debated. Giving fixed-duration schedule, prolonged time-to-next treatment and outcomes independent of genotype, CIT is still our preferred choice in WM. However, BTKi remain a valuable option in frail patients unsuitable for CIT.

Published
2022

10. P660: SEROLOGIC RESPONSE TO THE SECOND AND THIRD DOSE OF THE SARS-COV-2 VACCINE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: RESULTS OF A PROSPECTIVE, CENTRALIZED, MULTICENTER STUDY.

Author

Mauro, F. R., primary, Giannarelli, D., additional, Galluzzo, C., additional, Visentin, A., additional, Frustaci, A. M., additional, Sportoletti, P., additional, Vitale, C., additional, Reda, G., additional, Gentile, M., additional, Levato, L., additional, Murru, R., additional, Armiento, D., additional, Ielo, C., additional, Maglione, R., additional, Crisanti, E., additional, Cipiciani, A., additional, Mattiello, V., additional, Gianfelici, V., additional, Barabino, L., additional, Amici, R., additional, Coscia, M., additional, Tedeschi, A., additional, Trentin, L., additional, and Baroncelli, S., additional

Published
2022
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11. Efficacy of idelalisib and rituximab in relapsed/refractory chronic lymphocytic leukemia treated outside of clinical trials. A report of the Gimema Working Group

Author

Rigolin, G. M., Cavazzini, F., Piciocchi, A., Arena, V., Visentin, A., Reda, G., Zamprogna, G., Cibien, F., Vitagliano, O., Coscia, M., Farina, L., Gaidano, G., Murru, R., Varettoni, M., Paolini, R., Sportoletti, P., Pietrasanta, D., Molinari, A. L., Quaglia, F. M., Laurenti, L., Marasca, R., Marchetti, M., Mauro, F. R., Crea, E., Vignetti, M., Gentile, M., Montillo, M., Foa, R., Cuneo, A., Chiarenza, A., Perbellini, O., Mannina, D., Sancetta, R., Olivieri, A., Molica, S., Pane, F., Patti, C., Iliariucci, F., Gozzetti, A., Califano, C., Galieni, P., Augello, A. F., Vallisa, D., Cura, F., Frustaci, A. M., Fazi, P., Trentin, L., and Ferrara, F.

Subjects
Male, Oncology, Cancer Research, idelalisib, law.invention, 0302 clinical medicine, Randomized controlled trial, Recurrence, law, Original Research Articles, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Original Research Article, Chronic, Aged, 80 and over, Leukemia, real‐world evidence, Hematology, General Medicine, Middle Aged, Lymphocytic, Survival Rate, 030220 oncology & carcinogenesis, Female, Rituximab, Refractory Chronic Lymphocytic Leukemia, Idelalisib, chronic lymphocytic leukemia, real-world evidence, Aged, Disease-Free Survival, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Purines, Quinazolinones, medicine.drug, medicine.medical_specialty, NO, 03 medical and health sciences, Internal medicine, medicine, Survival rate, Performance status, business.industry, B-Cell, Clinical trial, Settore MED/15 - MALATTIE DEL SANGUE, Regimen, business, 030215 immunology
Abstract

Because the efficacy of new drugs reported in trials may not translate into similar results when used in the real‐life, we analyzed the efficacy of idelalisib and rituximab (IR) in 149 patients with relapsed/refractory chronic lymphocytic leukemia treated at 34 GIMEMA centers. Median progression‐free survival (PFS) and overall survival were 22.9 and 44.5 months, respectively; performance status (PS) ≥2 and ≥3 previous lines of therapy were associated with shorter PFS and overall survival (OS). 48% of patients were on treatment at 12 months; the experience of the centers (≥5 treated patients) and PS 0–1 were associated with a significantly longer treatment duration (p = 0.015 and p = 0.002, respectively). TP53 disruption had no prognostic significance. The overall response rate to subsequent treatment was 49.2%, with median OS of 15.5 months and not reached in patients who discontinued, respectively, for progression and for toxicity (p

Published
2021

12. Do age, fitness, and concomitant medications influence management and outcomes of patients with CLL treated with ibrutinib?

Author

Tedeschi, A, Frustaci, A, Mauro, F, Chiarenza, A, Coscia, M, Ciolli, S, Reda, G, Laurenti, L, Varettoni, M, Murru, R, Barate, C, Sportoletti, P, Greco, A, Borella, C, Rossi, V, Deodato, M, Biagi, A, Zamprogna, G, Pelle, A, Lapietra, G, Vitale, C, Morelli, F, Cassin, R, Fresa, A, Cavalloni, C, Postorino, M, Ielo, C, Cairoli, R, Di Raimondo, F, Montillo, M, Del Poeta, G, Tedeschi A., Frustaci A. M., Mauro F. R., Chiarenza A., Coscia M., Ciolli S., Reda G., Laurenti L., Varettoni M., Murru R., Barate C., Sportoletti P., Greco A., Borella C., Rossi V., Deodato M., Biagi A., Zamprogna G., Pelle A. C., Lapietra G., Vitale C., Morelli F., Cassin R., Fresa A., Cavalloni C., Postorino M., Ielo C., Cairoli R., Di Raimondo F., Montillo M., Del Poeta G., Tedeschi, A, Frustaci, A, Mauro, F, Chiarenza, A, Coscia, M, Ciolli, S, Reda, G, Laurenti, L, Varettoni, M, Murru, R, Barate, C, Sportoletti, P, Greco, A, Borella, C, Rossi, V, Deodato, M, Biagi, A, Zamprogna, G, Pelle, A, Lapietra, G, Vitale, C, Morelli, F, Cassin, R, Fresa, A, Cavalloni, C, Postorino, M, Ielo, C, Cairoli, R, Di Raimondo, F, Montillo, M, Del Poeta, G, Tedeschi A., Frustaci A. M., Mauro F. R., Chiarenza A., Coscia M., Ciolli S., Reda G., Laurenti L., Varettoni M., Murru R., Barate C., Sportoletti P., Greco A., Borella C., Rossi V., Deodato M., Biagi A., Zamprogna G., Pelle A. C., Lapietra G., Vitale C., Morelli F., Cassin R., Fresa A., Cavalloni C., Postorino M., Ielo C., Cairoli R., Di Raimondo F., Montillo M., and Del Poeta G.

Abstract

Functional reserve of organs and systems is known to be relevant in predicting immunochemotherapy tolerance. Age and comorbidities, assessed by the cumulative illness rating scale (CIRS), have been used to address chemotherapy intensity. In the ibrutinib era, it is still unclear whether age, CIRS, and Eastern Cooperative Oncology Group performance status (ECOG-PS) retain their predictive role on treatment vulnerability. In this series of 712 patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib outside clinical trials, baseline ECOG-PS and neutropenia resulted as the most accurate predictors of treatment feasibility and outcomes. Age did not independently influence survival and ibrutinib tolerance, indicating that not age per se, but age-related conditions, may affect drug management. We confirmed the role of CIRS . 6 as a predictor of a poorer progression- and event-free survival (PFS, EFS). The presence of a severe comorbidity was significantly associated with permanent dose reductions (PDRs), not translating into worse outcomes. As expected, del(17p) and/or TP53mut and previous therapies affected PFS, EFS, and overall survival. No study so far has analyzed the influence of concomitant medications and CYP3A inhibitors with ibrutinib. In our series, these factors had no impact, although CYP3A4 inhibitors use correlated with Cox regression analysis, with an increased risk of PDR. Despite the limitation of its retrospective nature, this large study confirmed the role of ECOG-PS as the most accurate predictor of ibrutinib feasibility and outcomes, and importantly, neutropenia emerged as a relevant tool influencing patients’ vulnerability. Although CIRS > 6 retained a significant impact on PFS and EFS, its value should be confirmed by prospective studies.

Published
2021

13. Intrahospital COVID-19 infection outbreak management: Keep calm and carry on

Author

Frustaci, A, Pioltelli, M, Ravano, E, Di Ruscio, F, Campisi, D, Puoti, M, Cairoli, R, Frustaci A. M., Pioltelli M. L., Ravano E., Di Ruscio F., Campisi D. A., Puoti M., Cairoli R., Frustaci, A, Pioltelli, M, Ravano, E, Di Ruscio, F, Campisi, D, Puoti, M, Cairoli, R, Frustaci A. M., Pioltelli M. L., Ravano E., Di Ruscio F., Campisi D. A., Puoti M., and Cairoli R.

Published
2021

14. Prognostic impact and risk factors of infections in patients with chronic lymphocytic leukemia treated with ibrutinib

Author

Mauro, F. R., Giannarelli, D., Visentin, A., Reda, G., Sportoletti, P., Frustaci, A. M., Chiarenza, A., Ciolli, S., Vitale, C., Laurenti, L., De Paoli, L., Murru, R., Gentile, M., Rigolin, G. M., Levato, L., Giordano, A., Del Poeta, G., Stelitano, C., Ielo, C., Noto, A., Guarente, V., Molica, S., Coscia, M., Tedeschi, A., Gaidano, G., Cuneo, A., Foa, R., Martelli, M., Girmenia, C., Gentile, G., Trentin, L., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Molica S., Tedeschi A., Foa R., Martelli M., Gentile G., Mauro, F. R., Giannarelli, D., Visentin, A., Reda, G., Sportoletti, P., Frustaci, A. M., Chiarenza, A., Ciolli, S., Vitale, C., Laurenti, L., De Paoli, L., Murru, R., Gentile, M., Rigolin, G. M., Levato, L., Giordano, A., Del Poeta, G., Stelitano, C., Ielo, C., Noto, A., Guarente, V., Molica, S., Coscia, M., Tedeschi, A., Gaidano, G., Cuneo, A., Foa, R., Martelli, M., Girmenia, C., Gentile, G., Trentin, L., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Molica S., Tedeschi A., Foa R., Martelli M., and Gentile G.

Abstract

Ibrutinib represents extraordinary progress in the treatment of chronic lymphocytic leukemia (CLL). However, treatment-related adverse events limit the benefit of this agent. This obser-vational, multicenter study focused on the incidence, risk factors, and prognostic impact of infections in 494 patients with CLL treated with an ibrutinib-based treatment. Ibrutinib was given to 89 (18%) previously untreated patients (combined with rituximab, 24) and 405 (82%) relapsed/refractory patients. Pneumonia (PN), grade ≥3 non-opportunistic infections (NOI), and opportunistic infections (OI) were recorded in 32% of patients with an overall incidence rate per 100 person-year of 15.3% (PN, 10%; NOI, 3.3%; OI, 2%). Infections were the reason for the permanent discontinuation of ibrutinib in 9% of patients. Patients who experienced pneumonia or a severe infection showed a significantly inferior survival than those who were infection-free (p < 0.0001). A scoring system based on the three factors associated with a significant and independent impact on infections—PN or severe infection in the year before starting ibrutinib, chronic obstructive pulmonary disease, ≥2 prior treatments—identified patients with a two-to threefold increase in the rate of infections. In conclusion, the results of this study highlight the adverse impact of infectious events on the outcomes of CLL patients treated with ibrutinib.

Published
2021

15. IBRUTINIB TOLERABILITY AND OUTCOME IN PATIENTS WITH HIGH‐RISK CHRONIC LYMPHOCYTIC LEUKEMIA

Author

Condoluci, A., primary, Terzi‐di‐Bergamo, L., additional, Forestieri, G., additional, Moia, R., additional, Deambrogi, C., additional, Deodato, M., additional, Frustaci, A. M., additional, Merli, M., additional, Mattarucchi, R., additional, Autore, F., additional, Fahrni, G., additional, Scarfò, L., additional, Gussetti, D., additional, Bulian, P., additional, Zanatta, A., additional, Spina, V., additional, Faderl, M. R., additional, Bruscaggin, A., additional, Pini, K., additional, Piffaretti, D., additional, Koch, R., additional, Pirosa, M. C., additional, Cittone, M. G., additional, Passweg, J., additional, Cavalli, F., additional, Zucca, E., additional, Gerber, B., additional, Gillessen, S., additional, Stüssi, G., additional, Gattei, V., additional, Ghia, P., additional, Gregor, M., additional, Laurenti, L., additional, Passamonti, F., additional, Tedeschi, A., additional, Gaidano, G., additional, and Rossi, D., additional

Published
2021
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16. ADAPTATION OF CHRONIC LYMPHOCYTIC LEUKEMIA TO IBRUTINIB IS MEDIATED BY EPIGENETIC PLASTICITY OF RESIDUAL DISEASE AND BY‐PASS SIGNALING VIA MAPK PATHWAY

Author

Terzi di Bergamo, L, primary, Forestieri, G, additional, Loh, J. W, additional, Singh, A, additional, Spina, V, additional, Zucchetto, A, additional, Condoluci, A, additional, Faderl, M, additional, Koch, R, additional, Bruscaggin, A, additional, Pini, K, additional, Wu, W, additional, Piffaretti, D, additional, Bittolo, T, additional, Tissino, E, additional, Paoli, L, additional, Deambrogi, C, additional, Frustaci, A. M, additional, Autore, F, additional, Merli, M, additional, Scarfò, L, additional, Rasi, S, additional, Passweg, J, additional, Moia, R, additional, Martines, C, additional, Ghia, P, additional, Cavalli, F, additional, Zucca, E, additional, Gerber, B, additional, Gillessen, S, additional, Stüssi, G, additional, Montillo, M, additional, Passamonti, F, additional, Gregor, M, additional, Laurenti, L, additional, Tedeschi, A, additional, Gaidano, G, additional, Efremov, D, additional, Gattei, V, additional, Khiabanian, H, additional, and Rossi, D, additional

Published
2021
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17. MOLTO, A MULTICENTER, OPEN LABEL, UNCONTROLLED, PHASE II CLINICAL TRIAL ON VENETOCLAX, ATEZOLIZUMAB, OBINUTUZUMAB IN RICHTER TRANSFORMATION: SAFETY INTERIM ANALYSIS

Author

Frustaci, A. M., primary, Tedeschi, A., additional, Zinzani, P. L., additional, Pietrasanta, D., additional, Coscia, M., additional, Zenz, T., additional, Motta, M., additional, Gaidano, G., additional, Scarfò, L., additional, Deodato, M., additional, Zamprogna, G., additional, Vitale, C., additional, Cairoli, R., additional, Rossi, D., additional, and Montillo, M., additional

Published
2021
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19. Younger patients with Waldenström Macroglobulinemia exhibit low risk profile and excellent outcomes in the era of immunotherapy and targeted therapies

Author

Varettoni, M., Ferrari, A., Frustaci, A. M., Ferretti, V. V., Rizzi, R., Motta, M., Piazza, F., Merli, M., Benevolo, G., Visco, C., Laurenti, L., Ferrero, S., Gentile, M., Del Fabro, V., Abbadessa, A., Klersy, C., Musto, P., Fabbri, N., Deodato, M., Dogliotti, I., Greco, C., Corbingi, A., Luminari, S., Arcaini, L., Rizzi R., Piazza F., Merli M., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Varettoni, M., Ferrari, A., Frustaci, A. M., Ferretti, V. V., Rizzi, R., Motta, M., Piazza, F., Merli, M., Benevolo, G., Visco, C., Laurenti, L., Ferrero, S., Gentile, M., Del Fabro, V., Abbadessa, A., Klersy, C., Musto, P., Fabbri, N., Deodato, M., Dogliotti, I., Greco, C., Corbingi, A., Luminari, S., Arcaini, L., Rizzi R., Piazza F., Merli M., Laurenti L. (ORCID:0000-0002-8327-1396), and Gentile M.

Abstract

We analyzed 160 young Waldenström Macroglobulinemia (WM) patients with a median age of 49 years (range 23-55 years), diagnosed between January 2000 and January 2019 in 14 Italian centers. At diagnosis, 70% of patients were asymptomatic. With a median follow-up of 5.6 years, 57% have been treated. As initial therapy 79% of patients received chemo-immunotherapy, 13% a chemo-free induction and 8% chemotherapy only. At relapse or progression, 6% underwent an autologous stem cell transplantation. Overall, 19% of patients received ibrutinib during the course of the disease. According to IPSSWM, 63% were classified as low risk, 27% as intermediate risk and 10% as high risk. Five-year OS was shorter in high-risk as compared with low or intermediate risk patients (92.9% vs 100% P =.002). According to revised IPSSWM, 92% were classified as very low or low risk and 8% as intermediate risk, with a shorter 5-year OS in the latter group (87.5% vs 100%, P =.028). The OS of young WM patients was not significantly reduced as compared with age-matched, sex-matched and calendar year-matched general population. Early diagnosis, absence of high-risk features in symptomatic patients and high efficacy of modern treatments are the main determinants of the excellent outcome of young WM patients.

Published
2020

21. Younger patients with Waldenström Macroglobulinemia exhibit low risk profile and excellent outcomes in the era of immunotherapy and targeted therapies

Author

Varettoni, Marzia, primary, Ferrari, Angela, additional, Frustaci, Anna M., additional, Ferretti, Virginia V., additional, Rizzi, Rita, additional, Motta, Marina, additional, Piazza, Francesco, additional, Merli, Michele, additional, Benevolo, Giulia, additional, Visco, Carlo, additional, Laurenti, Luca, additional, Ferrero, Simone, additional, Gentile, Massimo, additional, Del Fabro, Vittorio, additional, Abbadessa, Antonio, additional, Klersy, Catherine, additional, Musto, Pellegrino, additional, Fabbri, Nicole, additional, Deodato, Marina, additional, Dogliotti, Irene, additional, Greco, Corinna, additional, Corbingi, Andrea, additional, Luminari, Stefano, additional, and Arcaini, Luca, additional

Published
2020
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22. Analysis of the Bradyrhizobium japonicum hemH gene and its expression in Escherichia coli

Author

Frustaci, Jana M. and O'Brian, Mark R.

Subjects
Escherichia coli -- Research, Gene expression -- Analysis, Biological sciences
Abstract

Complementation analysis indicates that the Bradyrhizobium japonicum hemH gene is essential to free mutant strains I110ek4 and I110bk2 with respect to hemin auxotrophy, protoporphyrin accumulation and the lack in ferrochelatase activity. Its expression in Escherichia coli give 39-kDa proteins. The overexpressed protein indicates ferrochelatase activity, implying that the hemH gene encodes ferrochelatase. The B. japonicum hemH gene complements the Escherichia coli mutant by exhibiting hemin prototrophy, loss of protoporphyrin accumulation and expression of ferrochelatase activity.

Published
1993

23. Characterization of a Bradyrhizobium japonicum ferrochelatase mutant and isolation of the hemH gene

Author

Frustaci, Jana M. and O'Brian, Mark R.

Subjects
Rhizobium -- Genetic aspects, Microbial mutation -- Analysis, Hemoproteins -- Research, Biological sciences
Abstract

A Bradyrhizobium japonicum mutant defective in ferrochelatase, the last step in heme synthesis, was isolated and characterized. The mutant, strain I110ek4, was a strict hemin auxotroph. It accumulated the heme precursor protoporphyrin IX and was deficient in the activity of ferrochelatase. The putative protein encoded by the gene, designated hemH, was homologous to eukaryotic ferrochelatases. Furthermore, B. japonicum ferrochelatase is necessary for normal nodule development on soybean plants.

Published
1992

25. EFFICACY AND SAFETY OF MOLTO, A MULTICENTER, OPEN LABEL, PHASE II CLINICAL TRIAL EVALUATING VENETOCLAX, ATEZOLIZUMAB AND OBINUTUZUMAB COMBINATION IN RICHTER SYNDROME.

Author

Frustaci, A. M., Montillo, M., Rossi, D., Zinzani, P. L., Motta, M., Gaidano, G., Quaresmini, G., Scarfò, L., Pietrasanta, D., Coscia, M., Deodato, M., Zamprogna, G., Cairoli, R., Stüssi, G., Zucca, E., Pileri, S., Zenz, T., and Tedeschi, A.

Subjects
RICHTER syndrome, ATEZOLIZUMAB, VENETOCLAX, DIFFUSE large B-cell lymphomas, DNA repair
Abstract

RS mutation profile was tested on pre-treatment cell free DNA. Rate of unmeasurable MRD and impact of mutations and chronic lymphocytic leukemia-RS clonal relation on outcomes will be presented at the meeting. B Introduction: b Chemoimmunotherapy is the standard first line treatment of diffuse large B-cell lymphoma (DLBCL) variant of Richter syndrome (RS). [Extracted from the article]

Published
2023
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26. A phase II multi-center trial of pentostatin plus cyclophosphamide with ofatumumab in older previously untreated chronic lymphocytic leukemia patients

Author

Tedeschi, A, Rossi, D, Motta, M, Quaresmini, G, Rossi, M, Coscia, M, Anastasia, A, Rossini, F, Cortelezzi, A, Nador, G, Scarfo, L, Cairoli, R, Frustaci, A, Dalceggio, D, Picardi, P, de Paoli, L, Orlandi, E, Rambaldi, A, Massaia, M, Gaidano, G, Montillo, M, Tedeschi A., Rossi D., Motta M., Quaresmini G., Rossi M., Coscia M., Anastasia A., Rossini F., Cortelezzi A., Nador G., Scarfo L., Cairoli R., Frustaci A. M., Dalceggio D., Picardi P., de Paoli L., Orlandi E., Rambaldi A., Massaia M., Gaidano G., Montillo M., Tedeschi, A, Rossi, D, Motta, M, Quaresmini, G, Rossi, M, Coscia, M, Anastasia, A, Rossini, F, Cortelezzi, A, Nador, G, Scarfo, L, Cairoli, R, Frustaci, A, Dalceggio, D, Picardi, P, de Paoli, L, Orlandi, E, Rambaldi, A, Massaia, M, Gaidano, G, Montillo, M, Tedeschi A., Rossi D., Motta M., Quaresmini G., Rossi M., Coscia M., Anastasia A., Rossini F., Cortelezzi A., Nador G., Scarfo L., Cairoli R., Frustaci A. M., Dalceggio D., Picardi P., de Paoli L., Orlandi E., Rambaldi A., Massaia M., Gaidano G., and Montillo M.

Published
2015

28. Bendamustine and subcutaneous alemtuzumab combination is an effective treatment in relapsed/refractory chronic lymphocytic leukemia patients

Author

Montillo, M., primary, Tedeschi, A., additional, Gaidano, G., additional, Coscia, M., additional, Petrizzi, V. B., additional, Orlandi, E., additional, Cascavilla, N., additional, Ghia, P., additional, Motta, M., additional, Gallamini, A., additional, Frustaci, A. M., additional, Rossi, D., additional, De Paoli, L., additional, Nichelatti, M., additional, Morra, E., additional, and Massaia, M., additional

Published
2014
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29. Role of PET/CT in the Diagnostic Work-up of Patients with Chronic Lymphocytic Leukemia (CLL) and Clinical Signs of Disease Progression

Author

Mauro, Francesca R, primary, Riminucci, Mara, additional, Rossi, Davide, additional, Paoloni, Francesca, additional, Laurenti, Luca, additional, Frustaci, Anna M, additional, Cimino, Giuseppe, additional, Santopietro, Michelina, additional, Spadafora, Chiara, additional, Rago, Angela, additional, Autore, Francesco, additional, Matteo, Molica, additional, Simonetta, Brocchieri, additional, Nicolai, Emanuele, additional, Gaidano, Gianluca, additional, Guarini, Anna, additional, Paolo, Bianco, additional, and Foà, Robin, additional

Published
2012
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30. Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience

Author

Girmenia, C., primary, Frustaci, A. M., additional, Gentile, G., additional, Minotti, C., additional, Cartoni, C., additional, Capria, S., additional, Trisolini, S. M., additional, Matturro, A., additional, Loglisci, G., additional, Latagliata, R., additional, Breccia, M., additional, Meloni, G., additional, Alimena, G., additional, Foa, R., additional, and Micozzi, A., additional

Published
2011
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34. gsa1Is a Universal Tetrapyrrole Synthesis Gene in Soybean and Is Regulated by a GAGA Element (∗)

Author

Frustaci, Jana M., Sangwan, Indu, and O'Brian, Mark R.

Abstract

Expression of plant tetrapyrroles is high in photosynthetic tissues and in legume root nodules in the form of chlorophyll and heme, respectively. The universal tetrapyrrole precursor δ-aminolevulinic acid (ALA) is synthesized from glutamate 1-semialdehyde (GSA) by GSA aminotransferase in plants, which is encoded by gsa. Immunoblot analysis showed that GSA aminotransferase was expressed in soybean leaves and nodules, but not in roots, and that protein correlated with enzyme activity. These observations indicate that GSA aminotransferase expression is controlled in tetrapyrrole formation and argue against significant activity of an enzyme other than the well described aminotransferase for GSA-dependent ALA formation. gsamRNA and protein were induced in soybean nodules, and their activation was temporally intermediate between those of the respective early and late genes enod2and lb. A GSA aminotransferase gene, designated gsa1, was isolated and appears to be one of two gsagenes in the soybean genome. gsa1mRNA accumulated to high levels in leaves and nodules, but not in uninfected roots as discerned with a gsa1-specific probe. Message levels were higher in leaves from etiolated plantlets than in mature plants, and expression in the former was slightly elevated by light. The expression pattern of gsa1mRNA was qualitatively similar to that of total gsa. The data strongly suggest that gsa1is a universal tetrapyrrole synthesis gene and that a gsagene specific for a tissue, tetrapyrrole, or light condition is unlikely. The gsa1promoter contained a genetic element found in numerous Drosophila melanogastergenes; the so-called GAGA element displayed single-stranded character in vitroand formed a complex with nuclear factors from nodules and leaves but not from roots. From these observations we infer that the GAGA element is involved in the transcriptional control of gsa1.

Published
1995
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35. Refractory and 17p-deleted chronic lymphocytic leukemia: improving survival with pathway inhibitors and allogeneic stem cell transplantation

Author

Lucia Farina, Francesco Zallio, Daniele Vallisa, Andrea Ferrario, Francesco Barretta, M. Montillo, Lydia Scarfò, Francesco Onida, C. Salvetti, Benedetto Bruno, Massimo Magagnoli, G. Quaresmini, Marta Coscia, Francesca Patriarca, AM M. Frustaci, Paolo Corradini, Renato Fanin, Gianluigi Reda, Farina, L., Barretta, F., Scarfo', L., Bruno, B., Patriarca, F., Frustaci, A. M., Coscia, M., Salvetti, C., Quaresmini, G., Fanin, R., Onida, F., Magagnoli, M., Zallio, F., Vallisa, D., Reda, G., Ferrario, A., Corradini, P., and Montillo, M.

Subjects
Oncology, medicine.medical_specialty, Transplantation Conditioning, Allogeneic transplantation, BCR inhibitor, Chronic lymphocytic leukemia, chemistry.chemical_compound, Internal medicine, medicine, Humans, Transplantation, Homologous, Cumulative incidence, Progression-free survival, Retrospective Studies, Transplantation, Venetoclax, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Treatment Outcome, chemistry, Ibrutinib, Rituximab, business, Stem Cell Transplantation, medicine.drug
Abstract

Refractory/early relapsed and 17p deletion/p53 mutation (del(17p)/TP53mut)-positive chronic lymphocytic leukemia (CLL) has been conventionally considered a high-risk disease, potentially eligible for treatment with allogeneic stem cell transplantation (alloSCT). In this multicenter retrospective analysis of 157 patients, we compared the outcomes of patients with high-risk CLL treated with alloSCT, a B-cell receptor pathway inhibitor (BCRi), and both. Seventy-one patients were treated with BCRis, 67 patients underwent reduced-intensity conditioning alloSCT, and 19 received alloSCT with a BCRi before and/or after transplantation. Inverse probability of treatment weighting analyses were performed to compare the alloSCT and no-alloSCT groups; in the 2 groups, 5-year OS, PFS, and cumulative incidence of nonrelapse mortality (NRM) and relapse were 40% versus 60% (P = .096), 34% versus 17% (P = .638), 28% versus 5% (P = .016), and 38% versus 83% (P = .005), respectively. Patients treated with alloSCT plus BCRi had a 3-year OS of 83%. The 3-year OS and NRM by year of alloSCT, including patients treated with BCRi, were 53% and 17% in 2000 to 2007, 55% and 30% in 2008 to 2012, and 72% and 18% in 2013 to 2018. In conclusion, the combination of pathway inhibitors and alloSCT is feasible and may further improve the outcome of high-risk CLL patients.

Published
2020

36. First-line treatment of Waldenström's macroglobulinemia in Italy: A multicenter real-life study on 547 patients to evaluate the long-term efficacy and tolerability of different chemoimmunotherapy strategies.

Author

Autore F, Tedeschi A, Benevolo G, Mattiello V, Galli E, Danesin N, Rizzi R, Olivieri J, Cencini E, Puccini B, Ferrarini I, Marino D, Bullo M, Rossini B, Motta M, Innocenti I, Fresa A, Stirparo L, Petrilli D, Pasquale R, Musto P, Scapinello G, Noto A, Peri V, Zamprogna G, Hohaus S, Frustaci AM, Piazza F, Ferrero S, and Laurenti L

Published
2025
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37. Report of consensus panel 5 from the 11th international workshop on Waldenstrom's macroglobulinemia on COVID-19 prophylaxis and management.

Author

Terpos E, Branagan AR, García-Sanz R, Trotman J, Greenberger LM, Stephens DM, Morel P, Kimby E, Frustaci AM, Hatjiharissi E, San-Miguel J, Dimopoulos MA, Treon SP, and Leblond V

Subjects
Humans, COVID-19 Vaccines, Consensus, SARS-CoV-2, Antiviral Agents therapeutic use, Waldenstrom Macroglobulinemia drug therapy, Waldenstrom Macroglobulinemia prevention & control, Waldenstrom Macroglobulinemia diagnosis, COVID-19
Abstract

Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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38. Refractory and 17p-deleted chronic lymphocytic leukemia: improving survival with pathway inhibitors and allogeneic stem cell transplantation.

Author

Farina L, Barretta F, Scarfò L, Bruno B, Patriarca F, Frustaci AM, Coscia M, Salvetti C, Quaresmini G, Fanin R, Onida F, Magagnoli M, Zallio F, Vallisa D, Reda G, Ferrario A, Corradini P, and Montillo M

Subjects
Humans, Retrospective Studies, Stem Cell Transplantation, Transplantation Conditioning, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Leukemia, Lymphocytic, Chronic, B-Cell therapy
Abstract

Refractory/early relapsed and 17p deletion/p53 mutation (del(17p)/TP53mut)-positive chronic lymphocytic leukemia (CLL) has been conventionally considered a high-risk disease, potentially eligible for treatment with allogeneic stem cell transplantation (alloSCT). In this multicenter retrospective analysis of 157 patients, we compared the outcomes of patients with high-risk CLL treated with alloSCT, a B-cell receptor pathway inhibitor (BCRi), and both. Seventy-one patients were treated with BCRis, 67 patients underwent reduced-intensity conditioning alloSCT, and 19 received alloSCT with a BCRi before and/or after transplantation. Inverse probability of treatment weighting analyses were performed to compare the alloSCT and no-alloSCT groups; in the 2 groups, 5-year OS, PFS, and cumulative incidence of nonrelapse mortality (NRM) and relapse were 40% versus 60% (P = .096), 34% versus 17% (P = .638), 28% versus 5% (P = .016), and 38% versus 83% (P = .005), respectively. Patients treated with alloSCT plus BCRi had a 3-year OS of 83%. The 3-year OS and NRM by year of alloSCT, including patients treated with BCRi, were 53% and 17% in 2000 to 2007, 55% and 30% in 2008 to 2012, and 72% and 18% in 2013 to 2018. In conclusion, the combination of pathway inhibitors and alloSCT is feasible and may further improve the outcome of high-risk CLL patients., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Published
2020
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