Recent Advances in the Molecular Biology of Chronic Lymphocytic Leukemia: How to Define Prognosis and Guide Treatment.

Chronic Lymphocytic Leukemia (CLL) is the most frequent type of leukemia in Western countries. In recent years, there have been important advances in the knowledge of molecular alterations that underlie the disease's pathogenesis. Very heterogeneous prognostic subgroups have been identified by the mutational status of immunoglobulin heavy variable genes (), FISH analysis and molecular evaluation of mutations.

End of induction [F]FDG PET is prognostic for progression-free survival and overall survival in follicular lymphoma patients enrolled in the FOLL12 trial.

Purpose: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [F]FDG PET (PET) in follicular lymphoma patients.

Methods: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study.

New treatment options in elderly patients with Diffuse Large B-cell Lymphoma.

Most patients with Diffuse Large B-cell Lymphoma (DLBCL) are old (>65 years of age) and this population is expected to increase in the following years. A simplified geriatric assessment based on a careful evaluation of the fitness status and comorbidities is essential to choose the correct intensity of treatment. Fit older patients can benefit from a standard immunochemotherapy, while unfit/frail patients frequently need reduced doses or substitution of particular agents with less toxic ones.

Lenalidomide plus rituximab for the initial treatment of frail older patients with DLBCL: the FIL_ReRi phase 2 study.

Treatment of diffuse large B-cell lymphoma (DLBCL) in older patients is challenging, especially for those who are not eligible for anthracycline-containing regimens. Fondazione Italiana Linfomi (FIL) started the FIL_ReRi study, a 2-stage single-arm trial to investigate the activity and safety of the chemo-free combination of rituximab and lenalidomide (R2) in ≥70-year-old untreated frail patients with DLBCL. Frailty was prospectively defined using a simplified geriatric assessment tool.

A Fondazione Italiana Linfomi cohort study of R-COMP vs R-CHOP in older patients with diffuse large B-cell lymphoma.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the most commonly used regimen for the upfront treatment of diffuse large B-cell lymphoma (DLBCL). However, it is associated with cardiotoxicity, especially in older patients. Substituting doxorubicin with non-PEGylated liposomal doxorubicin (R-COMP) may reduce the risk of cardiac events, but its efficacy has never been demonstrated in prospective trials.

Long-term follow-up of rituximab plus bendamustine and cytarabine in older patients with newly diagnosed MCL.

The combination of rituximab, bendamustine, and low-dose cytarabine (R-BAC) has been studied in a phase 2 prospective multicenter study from Fondazione Italiana Linfomi (RBAC500). In 57 previously untreated elderly patients with mantle cell lymphoma (MCL), R-BAC was associated with a complete remission rate of 91% and 2-year progression-free survival (PFS) of 81% (95% confidence interval [CI], 68-89). Here, we report the long-term survival outcomes, late toxicities, and results of minimal residual disease (MRD) evaluation.

Biological features and outcome of diffuse large B-cell lymphoma associated with hepatitis C virus in elderly patients: Results of the prospective 'Elderly Project' by the Fondazione Italiana Linfomi.

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 comprehensive geriatric assessment. The aim of this study was to compare biological and clinical features of HCV positive (HCV+) with HCV negative (HCV-) cases.

Romidepsin-CHOEP followed by high-dose chemotherapy and stem-cell transplantation in untreated Peripheral T-Cell Lymphoma: results of the PTCL13 phase Ib/II study.

The standard treatment for young patients with untreated PTCLs is based on anthracycline containing-regimens followed by high-dose-chemotherapy and stem-cell-transplantation (HDT + SCT), but only 40% of them can be cured. Romidepsin, a histone-deacetylase inhibitor, showed promising activity in relapsed PTCLs; in first line, Romidepsin was added with CHOP. We designed a study combining romidepsin and CHOEP as induction before HDT + auto-SCT in untreated PTCLs (PTCL-NOS, AITL/THF, ALK-ALCL), aged 18-65 years.

High rate of durable responses with undetectable minimal residual disease with front-line venetoclax and rituximab in young, fit patients with chronic lymphocytic leukemia and an adverse biological profile: results of the GIMEMA phase II LLC1518 - VERITAS study.

The GIMEMA phase II LLC1518 VERITAS trial investigated the efficacy and safety of front-line, fixed-duration venetoclax and rituximab (VenR) in combination in young (≤65 years), fit patients with chronic lymphocytic leukemia and unmutated IGHV and/or TP53 disruption. Treatment consisted of the venetoclax ramp-up, six monthly courses of the VenR combination, followed by six monthly courses of venetoclax as a single agent. A centralized assessment of minimal residual disease (MRD) was performed by allele-specific oligonucleotide polymerase chain reaction assay on the peripheral blood and bone marrow at the end of treatment (EOT) and during the follow-up.

Diffuse large B-cell lymphoma in octogenarians aged 85 and older can benefit from treatment with curative intent: a report on 129 patients prospectively registered in the Elderly Project of the Fondazione Italiana Linfomi (FIL).

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 octogenarians [LO]) were underrepresented, and selection criteria were poorly defined.

The elderly prognostic index predicts early mortality in older patients with diffuse large B-cell lymphoma. An ad hoc analysis of the elderly project by the Fondazione Italiana Linfomi.

The Elderly Prognostic Index (EPI) is based on the integration of a simplified geriatric assessment, hemoglobin levels and International Prognostic Index 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 early mortality. This study included all patients registered in the Elderly Project for whom treatment details and a minimum follow-up of 3 months were available.

Ibrutinib improves survival compared with chemotherapy in mantle cell lymphoma with central nervous system relapse.

Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed/refractory MCL and penetrates the blood-brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019.

Treatment with Idelalisib in Patients with Relapsed or Refractory Follicular Lymphoma: The Observational Italian Multicenter FolIdela Study.

Follicular lymphoma (FL) is an indolent hematological disease, often responsive to the first line of treatment, but characterized by repeated relapses. The therapeutic algorithm for relapsed/refractory FL patients comprises phosphatidylinositol 3-kinase inhibitors. Idelalisib showed anticancer activity, while inducing a significant rate of toxicities.

Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study.

Purpose: We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy.

Methods: We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM.

Brentuximab vedotin consolidation after autologous stem cell transplantation for Hodgkin lymphoma: A Fondazione Italiana Linfomi real-life experience.

The standard management for relapsed or refractory classical Hodgkin lymphoma (cHL) is salvage therapy followed by autologous stem cell transplantation (ASCT). This strategy allows almost 50% of patients to be cured. Post-ASCT maintenance treatment with brentuximab vedotin (BV) confers improved progression-free survival (PFS) to cHL patients at high risk of relapse.

Allogeneic stem cell transplantation in patients with mantle cell lymphoma: results from the MANTLE-FIRST study on behalf of Fondazione Italiana Linfomi.

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 within the MANTLE-FIRST project. With a median follow-up of 3.

Clinical and prognostic role of sarcopenia in elderly patients with classical Hodgkin lymphoma: a multicentre experience.

Background: Elderly classical Hodgkin lymphoma (cHL) (ecHL) is a rare disease with dismal prognosis and no standard treatment. Fitness-based approaches may help design appropriate treatments. Sarcopenia has been associated with an increased risk of treatment-related toxicities and worse survival in various solid tumours, but its impact in ecHL is unknown.

Simplified Geriatric Assessment in Older Patients With Diffuse Large B-Cell Lymphoma: The Prospective Elderly Project of the Fondazione Italiana Linfomi.

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 Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion.

Long-lasting efficacy and safety of lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for or failed autologous transplantation.

We report final results of a phase II trial addressing efficacy and feasibility of lenalidomide maintenance in patients with chemosensitive relapse of diffuse large B-cell lymphoma (DLBCL) not eligible for or failed after autologous stem cell transplantation (ASCT). Patients with relapsed DLBCL who achieved at least a partial response to salvage chemoimmunotherapy were enrolled and treated with lenalidomide 25 mg/day for 21 of 28 days for 2 years or until progression or unacceptable toxicity. Primary endpoint was 1-year PFS.