A GIMEMA survey on therapeutic use and response rates of FLT3 inhibitors in acute myeloid leukemia: Insights from Italian real-world practice.

Given the limited data on the real-life therapeutic use of feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) inhibitors in Italy, we surveyed investigators at 59 Italian hematology centers to gain insight into the proportion of acute myeloid leukemia (AML) patients receiving FLT3 inhibitors and we collected data on the efficacy and safety of these agents. The survey results showed that in the real-life setting the response rate of the 3/7 + midostaurin regimen in newly diagnosed FLT3-mutated AML and of gilteritinib in the relapsed/refractory AML were comparable to that reported in the registrative clinical trials. The 3/7 + midostaurin treatment resulted in a 63% of complete remission (CR) rates and gilteritinib in a 44% of CR rates.

Financial toxicity and health-related quality of life in long-term survivors of acute promyelocytic leukaemia.

Objectives: We aimed to investigate the association between financial toxicity (FT) and the health-related quality of life profile of long-term survivors of acute promyelocytic leukaemia (APL) treated within a universal healthcare system.

Methods: We evaluated FT using the financial difficulties item of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). We also compared the prevalence of clinically important problems and symptoms between the survivors of APL with or without FT, using evidence-based thresholds for the EORTC QLQ-C30.

Decitabine in older patients with AML: quality of life results of the EORTC-GIMEMA-GMDS-SG randomized phase 3 trial.

We hypothesized that fit older patients with acute myeloid leukemia (AML) treated with decitabine (DEC) would report better health-related quality of life (HRQoL) outcomes than those receiving intensive chemotherapy (IC). We conducted a phase 3 randomized trial to compare DEC (10-day schedule) with IC (3+7) in older fit patients with AML. HRQoL was a secondary end point, and it was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in conjunction with its elderly module (EORTC QLQ-ELD14).

Unlocking the potential of synthetic patients for accelerating clinical trials: Results of the first GIMEMA experience on acute myeloid leukemia patients.

Artificial Intelligence has the potential to reshape the landscape of clinical trials through innovative applications, with a notable advancement being the emergence of synthetic patient generation. This process involves simulating cohorts of virtual patients that can either replace or supplement real individuals within trial settings. By leveraging synthetic patients, it becomes possible to eliminate the need for obtaining patient consent and creating control groups that mimic patients in active treatment arms.

Financial Toxicity and Health-Related Quality of Life Profile of Patients With Hematologic Malignancies Treated in a Universal Health Care System.

Purpose: We investigated the association of financial toxicity (FT) with the health-related quality of life (HRQoL) profile of patients with hematologic malignancies treated in a universal health care system.

Methods: We did a secondary analysis of six multicenter studies enrolling patients with hematologic malignancies. FT was evaluated using the financial difficulties item of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).

Long-Term Results of the Dasatinib-Blinatumomab Protocol for Adult Philadelphia-Positive ALL.

JCO We report the long-term results of the frontline trial with dasatinib and blinatumomab in induction/consolidation (GIMEMA LAL2116, D-ALBA) for adult Philadelphia-positive ALL (Ph+ ALL), which enrolled 63 patients of all ages. At a median follow-up of 53 months, disease-free survival, overall survival, and event-free survival are 75.8%, 80.

Italian Physicians' Perceptions about the Role of Asciminib in Later Lines Chronic Myeloid Leukemia in Clinical Practice: A GIMEMA Survey.

Unmet needs remain in later lines chronic myeloid leukemia (CML): the response rate and the overall survival of resistant patients in the chronic phase who changed a second-generation TKI in the second line with another TKI with similar action are usually poor, while the off-target toxicities and the potential development of mutations increase. The recent approval of asciminib, a STAMP inhibitor, in the third line, has the potential to soon change the therapeutic algorithm for this subset of patients. Here, we report the results of a GIMEMA survey assessing the number of patients currently treated in the third line in Italy, the current approach in later lines by Italian physicians, and the future role of this drug according to the reason to switch to asciminib (resistance and/or intolerance), as well as the perceptions about the future position of this agent.

Pegaspargase-modified risk-oriented program for adult acute lymphoblastic leukemia: results of the GIMEMA LAL1913 trial.

Pediatric-inspired chemotherapy is the standard of care for younger adults with Philadelphia chromosome-negative acute lymphoblastic leukemia/lymphoma (Ph- ALL/LL). In LAL1913 trial, the Gruppo Italiano Malattie EMatologiche dell'Adulto added pegaspargase 2000 IU/m2 to courses 1, 2, 5, and 6 of an 8-block protocol for patients aged from 18 to 65 years, with dose reductions in patients aged >55 years. Responders were risk stratified for allogeneic hematopoietic cell transplantation (HCT) or maintenance per clinical characteristics and minimal residual disease (MRD).

ENABLE: treatment combination including decitabine and venetoclax in acute myeloid leukemia secondary to myeloproliferative neoplasms.

The management of patients with acute myeloid leukemia (blast phase) secondary to myeloproliferative neoplasms (MPNs) is extremely challenging and the outcome dismal, with a median overall survival of about 3-6 months. Effective therapeutic approaches are lacking, especially when intensive strategies followed by allogeneic transplantation are not feasible. The combination of venetoclax and hypomethylating agents has recently been established as standard for newly diagnosed, unfit patients with acute myeloid leukemia, but the application of this therapeutic modality has not been tested prospectively in the specific context of blast-phase MPNs.

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.

Regulation 536/2014 and its beneficial impacts on academic clinical research in Italy. Closing the loop.

Regulation (EU) No 536/2014 (Clinical Trial Regulation, CTR) offers two precious tools to academic clinical research in Italy: - The right to transfer not-for-profit clinical trials data and results for registration purposes, and co-sponsorship. - The right to transfer data reduces the time needed to make innovative therapeutical agents and therapies accessible to the patient. Co-sponsorship, on the other hand, allows the establishment of a partnership between entities with different missions, ideals and attitudes, sharing - nevertheless - the same ultimate goal: meeting the patient's medical needs.

Neutralizing monoclonal antibodies in haematological patients paucisymptomatic for COVID-19: The GIMEMA EMATO-0321 study.

COVID-19 continues to be a relevant issue among patients with haematological malignancies (HM). Vaccines are frequently not effective in subjects on active treatment. In this multicentre retrospective study of Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA), we collected data from 91 paucisymptomatic HM patients treated with anti-spike neutralizing monoclonal antibodies (nMoAbs) to determine time to viral clearance, referencing it to the expected value of 28 days from an historical group of untreated paucisymptomatic patients.

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol.

IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19−86).

Physicians' Perceptions of Clinical Utility of a Digital Health Tool for Electronic Patient-Reported Outcome Monitoring in Real-Life Hematology Practice. Evidence From the GIMEMA-ALLIANCE Platform.

Digital health tools are increasingly being used in cancer care and may include electronic patient-reported outcome (ePRO) monitoring systems. We examined physicians' perceptions of usability and clinical utility of a digital health tool (GIMEMA-ALLIANCE platform) for ePRO monitoring in the real-life practice of patients with hematologic malignancies. This tool allows for the collection and assessment of ePROs with real-time graphical presentation of results to medical staff.

Efficacy of Front-Line Ibrutinib and Rituximab Combination and the Impact of Treatment Discontinuation in Unfit Patients with Chronic Lymphocytic Leukemia: Results of the Gimema LLC1114 Study.

The GIMEMA group investigated the efficacy, safety, and rates of discontinuations of the ibrutinib and rituximab regimen in previously untreated and unfit patients with chronic lymphocytic leukemia (CLL). Treatment consisted of ibrutinib, 420 mg daily, and until disease progression, and rituximab (375 mg/sqm, given weekly on week 1-4 of month 1 and day 1 of months 2-6). This study included 146 patients with a median age of 73 years, with IGHV unmutated in 56.

ELN2017 risk stratification improves outcome prediction when applied to the prospective GIMEMA AML1310 protocol.

The 2017 version of the European LeukemiaNet (ELN) recommendations, by integrating cytogenetics and mutational status of specific genes, divides patients with acute myeloid leukemia into 3 prognostically distinct risk categories: favorable (ELN2017-FR), intermediate (ELN2017-IR), and adverse (ELN2017-AR). We performed a post hoc analysis of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) AML1310 trial to investigate the applicability of the ELN2017 risk stratification to our study population. In this trial, after induction and consolidation, patients in complete remission were to receive an autologous stem cell transplant (auto-SCT) if categorized as favorable risk or an allogeneic stem cell transplant (allo-SCT) if adverse risk.

INCB84344-201: Ponatinib and steroids in frontline therapy for unfit patients with Ph+ acute lymphoblastic leukemia.

Tyrosine kinase inhibitors have improved survival for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, prognosis for old or unfit patients remains poor. In the INCB84344-201 (formerly GIMEMA LAL 1811) prospective, multicenter, phase 2 trial, we tested the efficacy and safety of ponatinib plus prednisone in newly diagnosed patients with Ph+ ALL ≥60 years, or unfit for intensive chemotherapy and stem cell transplantation.