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  1. Article ; Online: BTK Inhibitors in the Frontline Management of Waldenström Macroglobulinemia.

    Varettoni, Marzia / Matous, Jeffrey V

    Hematology/oncology clinics of North America

    2023  Volume 37, Issue 4, Page(s) 707–717

    Abstract: The discovery of MYD88 (L265P) mutation led to investigating BTK inhibitors in Waldenström macroglobulinemia (WM). Ibrutinib, the first-in-class agent, was approved based on a phase II trial in relapsed/refractory patients. In the phase III iNNOVATE ... ...

    Abstract The discovery of MYD88 (L265P) mutation led to investigating BTK inhibitors in Waldenström macroglobulinemia (WM). Ibrutinib, the first-in-class agent, was approved based on a phase II trial in relapsed/refractory patients. In the phase III iNNOVATE study, the combination of rituximab and ibrutinib was compared with rituximab and placebo in treatment-naïve and relapsed/refractory patients. Second-generation BTK inhibitor, zanubrutinib, was compared with Ibrutinib in MYD88-mutated WM patients in the phase III ASPEN trial, whereas acalabrutinib was investigated in a phase II trial. Here, we discuss the role of BTK inhibitors in treatment-naïve patients with WM based on currently available evidence.
    MeSH term(s) Humans ; Waldenstrom Macroglobulinemia/drug therapy ; Waldenstrom Macroglobulinemia/genetics ; Rituximab/therapeutic use ; Myeloid Differentiation Factor 88/genetics ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances Rituximab (4F4X42SYQ6) ; Myeloid Differentiation Factor 88 ; Protein Kinase Inhibitors
    Language English
    Publishing date 2023-05-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 93115-9
    ISSN 1558-1977 ; 0889-8588
    ISSN (online) 1558-1977
    ISSN 0889-8588
    DOI 10.1016/j.hoc.2023.04.005
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  2. Article ; Online: Identifying and addressing unmet clinical needs on the use of zanubrutinib in chronic lymphocytic leukemia: A consensus-based position paper from an ad hoc expert panel.

    Mauro, Francesca Romana / Tedeschi, Alessandra / Varettoni, Marzia / Zaja, Francesco / Barosi, Giovanni / Zinzani, Pier Luigi

    Hematological oncology

    2024  Volume 42, Issue 2, Page(s) e3255

    Abstract: Zanubrutinib has been approved for treating patients with different lymphoproliferative disorders and now represents a significant breakthrough in treating relapsed/refractory and previously untreated patients with chronic lymphocytic leukemia (CLL). ... ...

    Abstract Zanubrutinib has been approved for treating patients with different lymphoproliferative disorders and now represents a significant breakthrough in treating relapsed/refractory and previously untreated patients with chronic lymphocytic leukemia (CLL). Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of zanubrutinib in approved indications may be challenging. This article presents the results of a group discussion among an ad hoc constituted panel of experts to identify and address unmet clinical needs (UCNs) in using zanubrutinib in patients with CLL. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. Panel members reviewed the results of first-line and upstream controlled trials in which the efficacy and toxicity profile of zanubrutinib and other BTK inhibitors were investigated in patients with CLL. Based on a critical discussion of data, the panel produced recommendations for using zanubrutinib and proposals for new studies to increase the evidence for the optimal treatment of patients with CLL. The recommendations given by the panel are intended for use not only by expert centers but, above all, by less experienced hematologists as well as general practitioners.
    MeSH term(s) Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Consensus ; Pyrazoles/adverse effects ; Pyrimidines/adverse effects ; Protein Kinase Inhibitors/adverse effects ; Piperidines
    Chemical Substances zanubrutinib (AG9MHG098Z) ; Pyrazoles ; Pyrimidines ; Protein Kinase Inhibitors ; Piperidines
    Language English
    Publishing date 2024-02-16
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 604884-5
    ISSN 1099-1069 ; 0278-0232
    ISSN (online) 1099-1069
    ISSN 0278-0232
    DOI 10.1002/hon.3255
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  3. Article ; Online: Evaluating ibrutinib for the treatment of relapsed/refractory marginal zone lymphoma.

    Cavalloni, Chiara / Varettoni, Marzia / Rattotti, Sara / Arcaini, Luca

    Expert opinion on pharmacotherapy

    2021  Volume 22, Issue 13, Page(s) 1643–1649

    Abstract: ... ...

    Abstract Introduction
    MeSH term(s) Adenine/analogs & derivatives ; Humans ; Lymphoma, B-Cell, Marginal Zone/drug therapy ; Neoplasm Recurrence, Local ; Piperidines ; Pyrazoles/adverse effects ; Pyrimidines/adverse effects
    Chemical Substances Piperidines ; Pyrazoles ; Pyrimidines ; ibrutinib (1X70OSD4VX) ; Adenine (JAC85A2161)
    Language English
    Publishing date 2021-06-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2001535-5
    ISSN 1744-7666 ; 1465-6566
    ISSN (online) 1744-7666
    ISSN 1465-6566
    DOI 10.1080/14656566.2021.1941864
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  4. Article ; Online: New developments in the diagnosis and characterization of Waldenström's macroglobulinemia.

    García-Sanz, Ramón / Hunter, Zachary R / Poulain, Stéphanie / Varettoni, Marzia / Owen, Roger G

    Expert review of hematology

    2023  Volume 16, Issue 11, Page(s) 835–847

    Abstract: Introduction: Waldenström's macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) with immunoglobulin M (IgM) monoclonal gammopathy and morphologic evidence of bone marrow infiltration by LPL. Immunophenotyping and genotyping provide a ...

    Abstract Introduction: Waldenström's macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) with immunoglobulin M (IgM) monoclonal gammopathy and morphologic evidence of bone marrow infiltration by LPL. Immunophenotyping and genotyping provide a firm pathological basis for diagnosis and are particularly valuable in differential diagnosis between WM and related diseases. Emerging technologies in mutational analysis present new opportunities, but challenges remain around standardization of methodologies and reporting of mutational data across centers.
    Areas covered: The review provides an overview of the diagnosis of WM, with a particular focus on the role of immunophenotyping and genotyping.
    Expert opinion: Demonstration of LPL with a bone marrow biopsy is essential to reach a definitive diagnosis of WM. However,
    Language English
    Publishing date 2023-11-17
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2516804-6
    ISSN 1747-4094 ; 1747-4086
    ISSN (online) 1747-4094
    ISSN 1747-4086
    DOI 10.1080/17474086.2023.2270779
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  5. Article ; Online: Unmet clinical needs in the use of zanubrutinib in malignant lymphomas (Waldenström macroglobulinemia, marginal zone lymphoma and mantle cell lymphoma): A consensus-based position paper from an ad hoc expert panel.

    Zinzani, Pier Luigi / Mauro, Francesca Romana / Tedeschi, Alessandra / Varettoni, Marzia / Zaja, Francesco / Barosi, Giovanni

    Hematological oncology

    2023  Volume 41, Issue 5, Page(s) 795–808

    Abstract: Zanubrutinib has been approved for the treatment of patients with different lymphoproliferative disorders, and now represents a major breakthrough in the treatment of patients resistant or relapsing after the recommended therapies. Because few systematic ...

    Abstract Zanubrutinib has been approved for the treatment of patients with different lymphoproliferative disorders, and now represents a major breakthrough in the treatment of patients resistant or relapsing after the recommended therapies. Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of the drug in approved indications is challenging, and questions are emerging on its use in earlier stages of the disorders. This article presents the results of group discussion among an ad hoc constituted panel of experts aimed at identifying and addressing unmet clinical needs (UCNs) in the use of zanubrutinib in the lymphomas which have received the approval of use, specifically Waldenström macroglubulinemia, marginal zone lymphoma and mantle cell lymphoma. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. The panel produced recommendations and proposals for new studies for the management of the identified UCNs. These recommendations are intended for use not only by expert centers but above all by not experienced hematologists as well as general practitioners.
    MeSH term(s) Humans ; Adult ; Lymphoma, Mantle-Cell/drug therapy ; Lymphoma, Mantle-Cell/pathology ; Waldenstrom Macroglobulinemia/drug therapy ; Consensus ; Neoplasm Recurrence, Local ; Lymphoma, B-Cell, Marginal Zone/drug therapy
    Chemical Substances zanubrutinib (AG9MHG098Z)
    Language English
    Publishing date 2023-05-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 604884-5
    ISSN 1099-1069 ; 0278-0232
    ISSN (online) 1099-1069
    ISSN 0278-0232
    DOI 10.1002/hon.3172
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  6. Article: Gut Microbiota and B Cell Receptor (BCR) Inhibitors for the Treatment of Chronic Lymphocytic Leukemia: Is Biodiversity Correlated with Clinical Response or Immune-Related Adverse Event Occurrence? A Cross-Sectional Study.

    Zuccaro, Valentina / Petazzoni, Greta / Mileto, Irene / Corbella, Marta / Asperges, Erika / Sacchi, Paolo / Rattotti, Sara / Varettoni, Marzia / Defrancesco, Irene / Cambieri, Patrizia / Baldanti, Fausto / Arcaini, Luca / Bruno, Raffaele

    Microorganisms

    2023  Volume 11, Issue 5

    Abstract: Several studies have strengthened the link between the gut microbiota (GM) and the response to immunotherapy in patients with tumors, highlighting the potential role of GM as a biomarker of response. Targeted therapies including B-cell receptor (BCR) ... ...

    Abstract Several studies have strengthened the link between the gut microbiota (GM) and the response to immunotherapy in patients with tumors, highlighting the potential role of GM as a biomarker of response. Targeted therapies including B-cell receptor (BCR) inhibitors (BCRi) represent the newest approach to the treatment of chronic lymphocytic leukemia (CLL); however, not all patients achieve a satisfactory response, and immune-related adverse events (irAEs) can also impact the efficacy. The aim of the study was to compare GM biodiversity in patients with CLL, treated with BCRi for at least 12 months. Twelve patients were enrolled: 10 patients in the
    Language English
    Publishing date 2023-05-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms11051305
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  7. Article: Eosinophilic dermatosis of hematologic malignancy in patients with chronic lymphocytic leukemia/non-Hodgkin's B lymphoma: a single center prospective clinico-pathological study.

    Michelerio, Andrea / Tomasini, Carlo / Fiandrino, Giacomo / De Amici, Mara / Varettoni, Marzia / Defrancesco, Irene / Cavalloni, Chiara / Brazzelli, Valeria / Derlino, Federica / Paulli, Marco / Arcaini, Luca / Vassallo, Camilla

    Frontiers in medicine

    2023  Volume 10, Page(s) 1231003

    Abstract: Background: The pathogenesis of eosinophilic dermatosis of hematologic malignancy (EDHM) is poorly understood. Previously thought to be a hypersensitivity reaction to insect bites, immune dysregulation and cytokine imbalance are now thought to be ... ...

    Abstract Background: The pathogenesis of eosinophilic dermatosis of hematologic malignancy (EDHM) is poorly understood. Previously thought to be a hypersensitivity reaction to insect bites, immune dysregulation and cytokine imbalance are now thought to be responsible. Its prognostic significance is unclear.
    Objective: To describe the clinical, pathological and immunological findings in a series of oncohematological patients with EDHM.
    Methods: An observational prospective cohort study of oncohematological patients receiving a diagnosis of EDHM between April 2017 and December 2018.
    Results: A total of 15 patients with EDHM (10 females and 5 males) were identified among 422 oncohematological patients. Disease presentation varied from firm erythematous papules to more polymorphic presentations. The lesions were most prevalent on the exposed sites, 8/15 patients recalled an insect bite. Lesion seasonality was reported in 13/15 patients. IgE levels were elevated in six patients, circulating IL-4 and IL-5 were within a normal range. Twelve out of 15 patients developed skin manifestations after chemotherapy. The infiltrate could be eosinophil-rich or lymphocytic-rich. Interestingly, the histopathologic findings were in accordance with arthropod bites.
    Conclusion: A role for insect bites in EDHM is supported by our findings. EDHM may be related to aggressive hematologic disease.
    Language English
    Publishing date 2023-08-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1231003
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  8. Article: Second Neoplasms in Italian Patients with Hairy Cell Leukemia after Treatment with Cladribine: A Multicenter Investigation and Literature Review.

    Criscuolo, Marianna / Tosti, Maria Elena / Broccoli, Alessandro / Varettoni, Marzia / Maraglino, Alessio Maria Edoardo / Anastasia, Antonella / Cantonetti, Maria / Trentin, Livio / Kovalchuk, Sofia / Orsucci, Lorella / Deodato, Marina / Spolzino, Angelica / Volpetti, Stefano / Annibali, Ombretta / Storti, Sergio / Stelitano, Caterina / Marchesi, Francesco / Morè, Sonia / Fianchi, Luana /
    Falini, Brunangelo / Pulsoni, Alessandro / Tiacci, Enrico / Zinzani, Pier Luigi / Pagano, Livio

    Cancers

    2024  Volume 16, Issue 8

    Abstract: Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and ... ...

    Abstract Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.9 months (range: 9.2-169.7 months). All patients with solid neoplasms presented with a limited-stage disease, except four cases of locally advanced cancer; multiple myeloma patients had a smoldering disease, while lymphoma patients had stage Ie and stage IV diseases. Response to therapy was complete in 19 cases; 1 patient is still receiving treatment for a relapsing bladder disease, while 2 patients progressed during treatment and died. These two patients died from unrelated causes: one from infection and one due to surgery complications. The median OS from HCL was 98.5 months (range: 38.4-409.2 months), while the median OS from second cancer was 27.6 months (range: 1-117.8 months). The SIR was 0.86 (95% CI: 0.54-1.30) for males and 1.13 (95% CI: 0.36-2.73) for females: no statistically significant differences were highlighted. We were not able to demonstrate an excess of second cancer or a significant association with the specific studied neoplasm.
    Language English
    Publishing date 2024-04-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers16081475
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  9. Article ; Online: Systemic mastocytosis and lymphoplasmacytic lymphoma: an unusual and intriguing form of SM-AHN.

    Bonometti, Arturo / Boveri, Emanuela / Varettoni, Marzia / Ripamonti, Andrea / Fraticelli, Sara / Lucioni, Marco / Zibellini, Silvia / Elena, Chiara / Pietra, Daniela / Arcaini, Luca / Paulli, Marco

    Leukemia & lymphoma

    2021  Volume 62, Issue 7, Page(s) 1782–1785

    MeSH term(s) Humans ; Lymphoma, B-Cell ; Mast-Cell Sarcoma ; Mastocytosis, Systemic/diagnosis ; Mastocytosis, Systemic/genetics ; Myelodysplastic-Myeloproliferative Diseases ; Waldenstrom Macroglobulinemia/diagnosis
    Language English
    Publishing date 2021-02-14
    Publishing country United States
    Document type Letter
    ZDB-ID 1042374-6
    ISSN 1029-2403 ; 1042-8194
    ISSN (online) 1029-2403
    ISSN 1042-8194
    DOI 10.1080/10428194.2021.1885661
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    Zs.A 2997: Show issues Location:
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  10. Article ; Online: Molecular remission is an independent predictor of progression-free survival in patients with Waldenström macroglobulinemia treated with chemo-immunotherapy: Results from the FIL_BIOWM study.

    Varettoni, Marzia / Zibellini, Silvia / Merli, Michele / Drandi, Daniela / Jiménez, Cristina / Furlan, Daniela / Ferretti, Virginia Valeria / Fabbri, Nicole / Dogliotti, Irene / Varraso, Chiara / Ferrante, Martina / Cappello, Emilia / Peri, Veronica / Cavalloni, Chiara / Borriero, Michela / Facchetti, Giulia Vittoria / Ferrero, Simone / Arcaini, Luca / Garcia-Sanz, Ramon

    Hematological oncology

    2022  Volume 41, Issue 3, Page(s) 574–577

    MeSH term(s) Humans ; Waldenstrom Macroglobulinemia/drug therapy ; Progression-Free Survival ; Mutation ; Signal Transduction
    Language English
    Publishing date 2022-10-19
    Publishing country England
    Document type Letter
    ZDB-ID 604884-5
    ISSN 1099-1069 ; 0278-0232
    ISSN (online) 1099-1069
    ISSN 0278-0232
    DOI 10.1002/hon.3082
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