Michele Merli

Ospedale di Circolo e Fondazione Macchi Varese · Department of Hematology

TPS7094 Background: FL and MZL are indolent B-cell non-Hodgkin lymphomas (B-NHLs) that are treated in a similar way in the R/R setting. Despite the efficacy of rituximab–lenalidomide (R2) in patients (pts) with R/R FL, and MZL to a lesser extent, a notable proportion fail to achieve an optimal, durable response. Odronextamab is an off-the-shelf, CD...

e19057 Background: In ELM-2 (NCT03888105), a Ph 2, single arm, open label trial, odronextamab demonstrated robust efficacy, generally manageable safety, and overall maintenance of patient-reported outcomes (PROs) in R/R FL pts (Villasboas et al. ASH 2023). In FL, pts with disease progression within 2 yrs of frontline chemoimmunotherapy (POD24) are...

Few data are known regarding the use of interim positron emission tomography (iPET) after the first two cycles (iPET2) of chemotherapy in treatment‐naïve classical Hodgkin lymphoma (cHL) in routine clinical practice, and about the real‐life adoption of intensification strategies for iPET positive patients. We conducted a multicenter retrospective s...

Background Marginal zone lymphomas (MZL), comprised of three unique but related subtypes, lack a unifying prognostic score applicable to all the patients in need for systemic chemotherapy and/or immunotherapy. Methods Patients from the prospective NF10 study (NCT02904577) with newly diagnosed MZL and receiving frontline systemic therapy at diagnos...

Vaccinations are fundamental tools in preventing infectious diseases, especially in immunocompromised patients like those affected by non‐Hodgkin lymphomas (NHLs). The COVID‐19 pandemic made clinicians increasingly aware of the importance of vaccinations in preventing potential life‐threatening SARS‐CoV‐2‐related complications in NHL patients. Howe...

Hepatitis C virus (HCV)‐associated diffuse large B‐cell lymphoma (DLBCL) displays peculiar clinicopathological characteristics, but its molecular landscape is not fully elucidated. In this study, we investigated the clinicopathological and molecular features of 54 patients with HCV‐associated DLBCL. The median age was 71 years. An underlying margin...

The IELSG38 trial was conducted to investigate the effects of subcutaneous (SC) rituximab on the complete remission (CR) rate and the benefits of SC maintenance in patients with extranodal marginal zone lymphoma (MZL) who received frontline treatment with chlorambucil plus rituximab. Study treatment comprised an induction phase with chlorambucil 6...

This cohort study compares outcomes for patients with hematologic malignant tumors who prophylactically received tixagevimab-cilgavimab against SARS-CoV-2 with those who did not.

Introduction: The R-BAC regimen is considered among standard first-line treatments for elderly fit patients with mantle cell lymphoma (MCL). We previously reported (RBAC500 trial) a significantly inferior progression-free survival (PFS) for patients with high risk (HR) features, namely blastoid morphology and/or elevated Ki67 proliferative index, a...

Background The class of CD20×CD3 bispecific antibodies (BsAbs) has emerged as an important anti-lymphoma modality for patients (pts) with R/R B-cell non-Hodgkin lymphoma. Odronextamab, a novel, off-the-shelf, CD20×CD3 BsAb, has previously demonstrated compelling efficacy in both R/R diffuse large B-cell lymphoma and R/R FL. In pts with R/R FL, odro...

INTRODUCTION Interim PET (iPET) scan after 2 cycles has been proved a useful tool in order to escalate treatment in the setting of advanced stage (AS) classical Hodgkin Lymphoma (cHL) treated with ABVD as first-line therapy. However, few data are known regarding the use of iPET and the adoption of intensification treatment strategies in real life....

Background: Elderly patients with relapsed/refractory (R/R) FL have limited treatment options. Lenalidomide has direct tumoricidal and antiangiogenetic actions on tumor cells and is able to modulate tumor-cell microenvironment. Lenalidomide combined with Rituximab (R 2) in induction has shown a good clinical activity with low toxicity in both untre...

Introduction. MYD88 L265P is the hallmark mutation in Waldenström Macroglobulinemia (WM) and is becoming increasingly important in the management of IgM-gammopathies, due to its role as prognostic and predictive biomarker. Recently, MYD88 L265P detection by allele-specific quantitative PCR was proposed as reliable minimal residual disease (MRD) mar...

Background: Goals of patient-centered care for management of relapsed or refractory follicular lymphoma (R/R FL) are to improve clinical outcomes while maintaining or improving health-related quality of life (HRQoL). In ELM-2 (NCT03888105), a Phase 2, open-label, multicohort, multicenter study, odronextamab monotherapy demonstrated high and durable...

Introduction Ibrutinib was the first FDA-approved drug for patients (pts) with relapsed or refractory (R/R) marginal zone lymphomas (MZL), based on a phase 2 trial showing an overall response rate (ORR) of 58%, a median progression-free survival (PFS) of 15.7 months (mo) and an acceptable safety profile (Noy 2021). However, accelerated approval was...

Background. IPSSWM and revised-IPSSWM are the two currently prognostic scores used for survival prediction in symptomatic Waldenström Macroglobulinemia (WM) patients in need of treatment. In addition to age and serum beta-2 microglobulin levels, which are present in both scores, the IPSSWM includes anemia, thrombocytopenia and the concentration of...

Recent clinical studies demonstrated the achievement of lymphoma responses in patients with Hepatitis C virus‐associated indolent lymphoproliferative disorders (LPD) receiving direct‐acting antivirals (DAAs) as their sole treatment. However, the molecular mechanisms underlying LPD responses to DAAs are still poorly understood. In their paper the au...

Purpose: The combination of zanubrutinib plus obinutuzumab was found to be well tolerated with an early signal of efficacy in a phase 1b study. ROSEWOOD is a phase II, randomized study that assessed the efficacy and safety of zanubrutinib plus obinutuzumab versus obinutuzumab in patients with relapsed/refractory (R/R) follicular lymphoma (FL). Me...

R-CHOP is the most commonly used regimen worldwide for the upfront treatment of diffuse large B-cell lymphoma (DLBCL). However, it is associated with significant cardiotoxicity, especially in older patients. The R-COMP regimen, with non-pegylated liposomal doxorubicin, may reduce the risk of cardiac events, but its efficacy has never been demonstra...

7545 Background: In an early-phase study, the combination of zanubrutinib plus obinutuzumab (ZO) was well tolerated and associated with an early signal of efficacy in patients (pts) with follicular lymphoma (FL) (Tam et al. Blood Adv 2020). ROSEWOOD (NCT03332017) is a phase 2, randomized study designed to assess efficacy and safety of ZO vs obinutu...

We conducted a post hoc analysis of the FOLL12 trial to determine the impact of different initial immunochemotherapy (ICT) regimens on patient outcomes. Patients were selected from the FOLL12 trial, which included adults with stage II-IV follicular lymphoma (FL) grade 1-3a and high tumor burden. Patients were randomized 1:1 to receive either standa...

Castleman disease (CD) is a rare lymphoproliferative disorder that includes various clinico-pathological subtypes. According to clinical course, CD is divided into unicentric CD (UCD) and multicentric CD (MCD). MCD is further distinguished based on the etiological driver in herpes virus-8-related MCD (that can occur in the setting of HIV); in MCD a...

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity whose neoplastic cells retain a B-cell phenotype with expression of CD20. Radiotherapy is recommended for favorable stage IA disease while for other stages guidelines suggest therapeutic strategies similar to those used for classic HL. The role of rituximab, although quite wid...

BCL2 rearrangement is reported to be an early pathogenetic event in follicular lymphoma (FL) and it is considered as a reliable marker in the follow up of the disease. We aimed to investigate the frequency of BCL2 rearrangement in FLs from northwestern Italy, to evaluate their clinicopathological features, and to investigate alternative genetic abe...

Up to 10%–15% of diffuse large B‐cell lymphoma (DLBCL) are related to hepatitis C virus (HCV) infection, in particular in elderly patients. The Fondazione Italiana Linfomi has recently published a multicentre prospective observational study, the ‘Elderly Project’, on the outcome of DLBCL in patients aged ≥65 years, evaluated using a simplified comp...

Marginal zone lymphomas (MZLs) represent about 7% of B-cell non-Hodgkin lymphomas and include 3 different subtypes-namely, extranodal (EMZL), nodal, and splenic (SMZL). The initial assessment requires specific diagnostic and staging procedures depending on organ-related peculiarities. In particular, although positron emission tomography/computed to...

Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged >85 (late o...

COVID-19, the disease caused by SARS-CoV-2, is still afflicting thousands of people across the globe. Few studies on COVID-19 in chronic lymphocytic leukemia (CLL) are available. Here, we analyzed data from the CLL cohort of the Italian Hematology Alliance on COVID-19 (NCT04352556), which included 256 CLL patients enrolled between February 25, 2020...

The Elderly Prognostic Index (EPI) is based on the integration of a simplified geriatric assessment (sGA), haemoglobin levels and International Prognostic Index (IPI) and has been validated to predict overall survival in older patients with diffuse large B‐cell lymphoma (DLBCL). In this study, we evaluated the ability of EPI to predict the risk of...

Patients with Philadelphia-negative myeloproliferative neoplasms are at high risk of thrombotic events (TEs). Predisposing factors have been identified in essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (primary MF, PMF), while yet not recognized in post PV/ET-MF (known as secondary MF, SMF). Within the 1258 SMF of...

PURPOSE We prospectively treated patients with hepatitis C virus (HCV)–associated indolent lymphomas with genotype-appropriate direct-acting antivirals (DAAs) with the aim to evaluate virologic and hematologic outcomes. No prospective studies in this setting have been published so far. METHODS FIL_BArT is a prospective, multicenter, phase II trial...

Background: Castleman disease (CD) is a rare limphoproliferative disease with uncertain pathogenesis and comprising a group of disorders with similar histopathology but variable ethiology, clinical presentations, terapies and outcome. It can be divided in unicentric (UCD) or multicentric (MCD), this second entity encompasses HHV8+ MCD, POEMS-associ...

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e19544 Background: Maintenance in FL patients (pts) improves progression free survival (PFS). SARS-Cov2 pandemic posed unique challenges for immunocompromised pts. Methods: This is an observational, multicenter, retrospective and prospective study. The aim is to evaluate the outcome of FL pts in maintenance with antiCD20-MoAb during SARS-Cov2 pande...

7510 Background: FL is the most common type of indolent non-Hodgkin lymphoma. Approved treatment options are limited for pts with R/R FL. In a phase 1b trial ( Blood Adv. 2020;4(19):4802-4811), ZO was found to be tolerable and associated with early signal of efficacy. ROSEWOOD (BGB-3111-212) is a phase 2, randomized study designed to assess efficac...

This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Checkpoint inhibitors (CPIs) are routinely employed in relapsed/refractory classical Hodgkin lymphoma. Nonetheless, persistent long‐term responses are uncommon, and one‐third of patients are refractory. Several reports have suggested that treatment with CPIs may re‐sensitize patients to chemotherapy, however there is no consensus on the optimal che...

Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have a poor prognosis, with an expected survival of less than 1 year using standard salvage therapies. Recent advances in our understanding of the biology of PTCL have led to identifying B-Cell Lymphoma 2 (BCL2) protein as a potential therapeutic target. BLC2 inhibitor veneto...

Background: Hepatitis C virus (HCV) chronic infection has been associated with increased risk of non-Hodgkin lymphoma (NHL) in people living with human immunodeficiency virus (HIV) as well as with a trend of inferior overall survival (OS) in HIV-associated NHL in the modern antiretroviral therapy (ART) era (Besson 2020). The recent introduction of...

Introduction. The administration of immuno-chemotherapy (ICT) followed by rituximab maintenance (RM) is the recommended approach for the front-line therapy of high tumor burden follicular lymphoma (HTB-FL) patients. Among available ICT regimens, RB (Rituximab-bendamustine) and R-CHOP regimen, are preferred options with high, similar efficacy. Regar...

Introduction Symptomatic patients with relapsed/refractory Waldenström Macroglobulinemia (RR-WM) treated with standard rituximab plus chemotherapy as second-line salvage therapy, generally show a 18-months progression free survival (PFS) of about 50%. On behalf of the Fondazione Italiana Linfomi, a multicenter phase II study was designed to assess...

BACKGROUND. HCV-positive DLBCL has distinct clinical and pathologic characteristics compared to its negative counterpart: patients (pts) are usually older with more frequent splenic and extranodal involvement and elevated LDH. Differently from its clinical hallmarks, the molecular landscape of this pathological entity has been scarcely outlined. ME...

Introduction Non-pegylated liposomal doxorubicin (NPLD) is considered a good alternative to conventional doxorubicin for the treatment of older patients (pts) with aggressive lymphomas and/or at high risk for cardiological toxicity. The use of R-COMP for the treatment of older pts with DLBCL has been supported by several small retrospective studies...

The R-BAC regimen is considered among standard first-line treatment for elderly fit patients with mantle cell lymphoma (MCL). In the previous R-BAC500 FIL trial, patients with the blastoid variant and/or high Ki67 proliferative index (High Risk - HR-) had a significantly higher risk of progression (2-years PFS of 40%), as compared to classical hist...

The role of allogeneic stem cell transplantation (allo-SCT) in mantle cell lymphoma (MCL) is uncertain, even more in the era of bruton's tyrosine kinase inhibitors (BTKi) and chimeric antigen receptor T-cells. We retrospectively analyzed 55 patients who underwent allo-SCT for MCL relapsed or refractory (r/r) after rituximab and high-dose cytarabine...

Context Ibrutinib inhibits BTK with the most typical response in CLL being partial remission (PR) with measurable minimal residual disease (MRD) in blood. Remission is usually maintained until development of genetically-driven resistance. Objective Mechanism of adaptation and survival in MRD. Patients and Methods Pre-treatment CLL cells and under...

Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their...

In IgM monoclonal gammopathies MYD88L265P is a prognostic and predictive biomarker of therapy response. MYD88L265P detection is mainly performed by allele-specific quantitative PCR (ASqPCR), however recently, droplet digital PCR (ddPCR) has been proved to be suitable for MYD88L265P screening and minimal residual disease monitoring (MRD). This study...

PURPOSE To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL). METHODS We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linf...

Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1-negative clonal disorder, which belongs to the myelodysplastic/ myeloproliferative group. This disease is characterized by recurrent somatic mutations in SETBP1, ASXL1 and ETNK1 genes, as well as high genetic heterogeneity, thus posing a great therapeutic challenge. To provide a comprehensive g...

Background. The World Health Organization defines Waldenström Macroglobulinemia (WM) as a lymphoplasmacytic lymphoma associated with a serum immunoglobulin M (IgM) monoclonal protein. Since bone marrow (BM) infiltration is always present, while extramedullary involvement is infrequent, trephine BM biopsy is mandatory based on currently used diagnos...

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‐im...

Hepatitis C virus infection represents a global health problem with 3% of population infected worldwide. Several epidemiological studies have shown an increased risk of B cell non-Hodgkin lymphomas in HCV-infected subjects with a wide geographic variability. The observation that HCV eradication by antiviral treatment is associated with successful l...

Primary pancreatic lymphoma (PPL) is a rare disease representing 0.1% of malignant lymphomas, which lacks well‐defined diagnostic and therapeutic protocols. Objectives To describe PPL clinical, diagnostic and histological characteristics, together with therapy and outcome, in a relatively large series of patients. Methods The study includes 39 PP...

Recent studies have demonstrated feasibility and substantial benefit of direct-acting antivirals (DAAs) administration during or after first-line immune-chemotherapy (I-CT) in patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphomas (DLBCL). However, data on DAAs used during or after salvage treatments are still lacking. In thi...

Diagnosis of non-CLL B Cell Chronic Lymphoproliferative Disorders (BCLPD), defined by the detection of peripheral blood (PB) B-Cell clone with flow cytometry (FC) Matutesscore≤3, is not an infrequent event in clinical daily practice. Only a portion of these cases may be actually classified according to the 2016 revision of WHO classification of lym...

Background: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms that can progress to post-PV (PPV) myelofibrosis (MF) and post-ET (PET) MF, also known as secondary myelofibrosis (SMF). The 2009 International Working Group for Myelofibrosis Research and Treatment group (IWG-MRT) diagnostic criteria for SMF requ...

Background. Waldenström Macroglobulinemia (WM) is a rare indolent lymphoma typical of the elderly population, with a median age at diagnosis of 65-70 years and median overall survival of approximately 10 years. Age is the most important prognostic factor in WM, and unrelated mortality significantly impacts survival in elderly patients. The past two...