Publications by authors named "Giulia Zamprogna"

9 Publications

  • Page 1 of 1

Identification of a Candidate Gene Set Signature for the Risk of Progression in IgM MGUS to Smoldering/Symptomatic Waldenström Macroglobulinemia (WM) by a Comparative Transcriptome Analysis of B Cells and Plasma Cells.

Cancers (Basel) 2021 Apr 12;13(8). Epub 2021 Apr 12.

Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy.

Waldenström Macroglobulinemia (WM) is a B-cell lymphoma characterized by the precursor condition IgM monoclonal gammopathies of undetermined significance (IgM MGUS). We performed a gene expression profiling study to compare the transcriptome signatures of bone marrow (BM) B-cells and plasma cells of 36 WM patients, 13 IgM MGUS cases, and 7 healthy subjects used as controls (CTRLs) by Affymetrix microarray. We determined 2038 differentially expressed genes (DEGs) in CD19+ cells and 29 DEGs genes in CD138+ cells, respectively. The DEGs identified in B-cells were associated with KEGG pathways, mainly involved in hematopoietic cell lineage antigens, cell adhesion/focal adhesion/transmembrane proteins, adherens junctions, Wnt-signaling pathway, BCR-signaling pathway, calcium signaling pathway, complement/coagulation cascade, platelet activation, cytokine-cytokine receptor interactions, and signaling pathways responsible for cell cycle, apoptosis, proliferation and survival. In conclusion, we showed the deregulation of groups of genes belonging to KEGG pathways in the comparison among WM vs. IgM MGUS vs. CTRLs in B-cells. Interestingly, a small set of genes in B-cells displayed a common transcriptome expression profile between WM and IgM MGUS compared to CTRLs, suggesting its possible role in the risk of transformation of IgM MGUS to WM.
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http://dx.doi.org/10.3390/cancers13081837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070603PMC
April 2021

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

Hematol Oncol 2021 Mar 19. Epub 2021 Mar 19.

Department of Medical Sciences, Hematology Section, University of Ferrara, Cona - Ferrara, Italy.

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 < 0.01). Treatment breaks ≥14 days were recorded in 96% of patients and adverse events mirrored those reported in trials. In conclusion, this real-life analysis showed that IR treatment duration was longer at experienced centers, that the ECOG PS and ≥3 lines of previous therapy are strong prognostic factor and that the overall outcome with this regimen was superimposable to that reported in a randomized trial.
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http://dx.doi.org/10.1002/hon.2861DOI Listing
March 2021

Pre-existing and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs.

Blood 2021 Mar 2. Epub 2021 Mar 2.

University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.

Autoimmune cytopenias (AIC) affect 5-9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs - ibrutinib, idelalisib and venetoclax - have a prominent role in the treatment of CLL, but their impact on CLL-associated AIC is largely unknown. In this study, we evaluated the characteristics and outcome of pre-existing AIC, and described the incidence, quality and management of treatment-emergent AIC during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of pre-existing AIC was reported in 104/815 patients (13%). Interestingly, 80% of patients whose AIC was not resolved at the time of targeted drug start experienced an improvement or a resolution during therapy. Treatment-emergent AIC occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib and in 7% during venetoclax, with an estimated incidence rate of 5, 6 and 69 episodes per 1000 patients per year of exposure in the three treatment groups, respectively. The vast majority of patients who developed treatment-emergent AIC carried unfavorable biological features such as an unmutated IGHV, and a del(17p) and/or TP53 mutation. Notably, despite AIC, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib and venetoclax appears to have a beneficial impact on CLL-associated AIC, inducing an improvement or even a resolution of pre-existing AIC in most cases and eliciting treatment-emergent AIC in a negligible portion of patients.
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http://dx.doi.org/10.1182/blood.2020008201DOI Listing
March 2021

The management of chronic lymphoproliferative disorders at the time of SARS-Covid2 pandemic: weathering the storm.

Leuk Lymphoma 2020 12 23;61(13):3278-3279. Epub 2020 Jul 23.

Department of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy.

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http://dx.doi.org/10.1080/10428194.2020.1797011DOI Listing
December 2020

Duvelisib for the treatment of chronic lymphocytic leukemia.

Expert Opin Pharmacother 2020 Aug 15;21(11):1299-1309. Epub 2020 Apr 15.

Dept of Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3 , Milano, Italy.

Introduction: Duvelisib, a first in class, oral, dual PI3 k-delta/gamma inhibitor recently received FDA approval for previously treated CLL (chronic lymphocytic leukemia)/SLL (small lymphocytic lymphoma) and follicular lymphoma. Data coming from the phase III 'DUO' trial, in fact, showed a superior progression-free survival (PFS) in CLL patients treated with duvelisib compared to ofatumumab.

Areas Covered: This review provides analysis of the mechanism of action of duvelisib and includes the rationale for the use of double inhibition. The authors also give their clinical experience with duvelisib. Overall, despite the high efficacy of the drug, some concern remains on duvelisib-related adverse events leading to treatment interruption in a significant proportion of patients.

Expert Opinion: Considering the unmet need of salvage therapies in patients failing BTK and/or Bcl2 inhibitors, treatment with duvelisib represents a new valid option in the CLL therapeutic armamentarium. Therefore, the correct management of adverse events with early treatment suspension, dose reductions and prompt supportive treatment could help to manage treatment, thus improving patient outcome. Finally, the association of duvelisib with other targeted therapies, such as ibrutinib or venetoclax, could allow clinicians to capitalize on the synergistic activity of these agents.
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http://dx.doi.org/10.1080/14656566.2020.1751123DOI Listing
August 2020

Health-related quality of life in Waldenstrom Macroglobulinemia and IgM-related disorders: A single institution experience.

Hematol Oncol 2020 Feb 18;38(1):111-113. Epub 2019 Dec 18.

ASST Grande Ospedale Metropolitano Niguarda, Department of Hematology, Niguarda Cancer Center, Milan, Italy.

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http://dx.doi.org/10.1002/hon.2699DOI Listing
February 2020

Duvelisib: a new phosphoinositide-3-kinase inhibitor in chronic lymphocytic leukemia.

Future Oncol 2019 Jul 29;15(19):2227-2239. Epub 2019 May 29.

Department of Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, Milano, Italy.

P110-γ and -δ act in lymphocytes chemotaxis, presenting distinct, nonredundant roles in B- and T-cell migration and adhesion to stromal cells. Moreover, phosphoinositide-3-kinase-γ inhibition contributes to regulate macrophage polarization inhibiting cancer growth. Duvelisib (IPI-145) is an oral first-in-class, dual phosphoinositide-3-kinase inhibitor targeting p110-δ/γ exerting its activity in preclinical studies across different prognostic groups. In a large Phase III study, duvelisib showed superior progression-free survival and overall response rate compared with ofatumumab, thus leading to its approval for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Immune-related effects are the main reason for treatment suspension, thus affecting survival benefit. Nevertheless, the correct management of adverse events, eventually including dose modification, allows patients to remain on treatment. In conclusion, duvelisib represents a promising treatment in chronic lymphocytic leukemia and a salvage therapy after ibrutinib.
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http://dx.doi.org/10.2217/fon-2018-0881DOI Listing
July 2019

Ibrutinib for the treatment of chronic lymphocytic leukemia.

Expert Rev Hematol 2019 05 11;12(5):273-284. Epub 2019 Apr 11.

a Department of Hematology , Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda , Milano , Italy.

Introduction: Chemoimmunotherapy has improved outcomes in chronic lymphocytic leukemia, yet it is not curative, with very high relapse rates, and is associated with a significant risk of toxicities. Moreover, patients with higher-risk genetic abnormalities continue to experience poorer outcomes and lower survival. Recently, novel targeted therapies have been developed to increase efficacy and reduce toxicity. Areas covered: Ibrutinib is an oral irreversible inhibitor of Bruton's tyrosine kinase, a mediator of B-cell receptor signaling, which plays a vital role in various B-cell neoplasms. The drug has been approved for the treatment of several hematological malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma, where large trials have shown outcomes never seen before even in high-risk patients. The safety profile appeared furthermore favorable, even in elderly and unfit patients. Expert opinion: Therapy with ibrutinib rarely provides MRD-negative complete remission; an indefinite maintenance is therefore needed, with the risk of developing adverse events (AE) or resistance resulting in treatment interruption or discontinuation. Novel, extremely promising, combination strategies, based on the association of ibrutinib with chemoimmunotherapy, anti-CD20 monoclonal antibody or other targeted agents, are currently being investigated, with the goal of achieving greater depth of remission, especially MRD-negativity, and removing the need for indefinite treatment.
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http://dx.doi.org/10.1080/17474086.2019.1597703DOI Listing
May 2019