Pegaspargase administration and tolerability in patients aged 55 years or older with acute lymphoblastic leukemia treated with the LAL1913 program. A subanalysis of the Campus ALL group.

The adoption of pediatric-inspired regimens for the treatment of Ph-negative acute lymphoblastic leukemia (ALL) in adults has improved prognosis. However, the feasibility of these intensive regimens in older patients is limited, due to the increased incidence of therapy-related side effects, including those related to asparaginase. In this sub-analysis carried out by the Campus ALL network, 90 ALL patients aged 55 or more (median age 59 years) homogeneously treated in real-life according to the GIMEMA LAL1913 program, were analyzed to evaluate the feasibility and tolerability of pegaspargase (PEG-ASP) treatment.

Gilteritinib in FLT3-mutated acute myeloid leukemia: A real-world Italian experience.

Background And Methods: This real-world study evaluated the clinical effectiveness of gilteritinib in 205 patients with relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) enrolled in the Italian expanded access since January 2018.

Results: Of the 205 patients, 124 (60.5%) received gilteritinib as a bridging therapy to allogeneic stem cell transplantation (allo-SCT), achieving complete remission in 52.

Real World Incidence and Etiology of Infectious Complications in Adults With Ph-Negative Acute Lymphoblastic Leukemia Treated With the Pediatric-Inspired GIMEMA LAL1913 Program. A Campus All Study.

Infections often complicate pediatric-inspired treatments for adult Philadelphia-negative acute lymphoblastic leukemia (Ph- ALL). Literature data on these complications are difficult to interpret due to the heterogeneity of types of infections analyzed or patients and treatment characteristics. A deeper insight on the infections occurring in the real life in uniformly treated ALL patients is lacking.

Matching-adjusted indirect comparison of CPX- 351 in secondary Acute Myeloid Leukemia between the registrative trial and a real-life study.

A real-life study on CPX-351 and the standard arm ('7 + 3') of the CPX-351 registrative trial in adults with secondary Acute Myeloid Leukemia were compared by an unanchored Matching-adjusted indirect comparison (MAIC), in order to evaluate the efficacy and toxicity of CPX-351. Results of this study are important to confirm the role of CPX-351 in significantly improving survival and remission rates compared with '7 + 3' with a good safety profile in AML patients with high-risk features, a target group traditionally with a very poor prognosis. Moreover, this pilot analysis underlines the potentiality of the statistical method to compare studies with strong differences.

Safety run-in and part 1 of GIMEMA AML1718: venetoclax combined with FLAI as induction treatment in non-low-risk AML.

The standard induction treatment for acute myeloid leukemia (AML) has limited efficacy for patients with non-low-risk AML. We conducted a multicenter study phase 1b/2, Gruppo Italiano Malattie EMatologiche dell'Adulto AML1718, to investigate the safety and efficacy of venetoclax (VEN) combined with fludarabine, cytarabine, and idarubicin (V-FLAI) as an induction therapy for patients with non-low-risk AML aged <65 years and at intermediate or high European LeukemiaNet risk. After a safety run-in, patients were randomly allocated to VEN 400 mg or VEN 600 mg cohorts.

Impact of Pre-Treatment Comorbidity Burden on Survival in Patients Receiving Venetoclax Plus Hypomethylating Agents.

Expectation of survival of patients receiving HMA + VEN is influenced by pre-treatment comorbidity burden.

NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma.

Elevated levels of the NAD+-generating enzyme nicotinamide phosphoribosyltransferase (NAMPT) are a common feature across numerous cancer types. Accordingly, we previously reported pervasive NAD+ dysregulation in multiple myeloma (MM) cells in association with upregulated NAMPT expression. Unfortunately, albeit being effective in preclinical models of cancer, NAMPT inhibition has proven ineffective in clinical trials because of the existence of alternative NAD+ production routes using NAD+ precursors other than nicotinamide.

Comparing Outcomes Between CPX-351 and Fludarabine-Based Induction in Secondary Acute Myeloid Leukemia in the Real-World Setting: The Prognostic Role of Measurable Residual Disease.

Secondary acute myeloid leukemia (s-AML) is associated with inferior outcomes with conventional chemotherapy, and fludarabine combinations (FLAG-Ida) have been tested to improve results. More recently, CPX-351 resulted superior to conventional 3 + 7 in s-AML patients. In the UK NCRI AML19 trial, AML patients were randomized to receive either FLAG-Ida or CPX-351.

Clonal hematopoiesis impacts frailty in newly diagnosed multiple myeloma patients: a retrospective multicenter analysis.

Somatic mutations of hematopoietic cells in the peripheral blood of normal individuals refer to clonal hematopoiesis of indeterminate potential (CHIP), which is associated with a 0.5-1% risk of progression to hematological malignancies and cardiovascular diseases. CHIP has also been reported in Multiple Myeloma (MM) patients, but its biological relevance remains to be elucidated.

Long-term real-world evidence of CPX-351 of high-risk patients with AML identified high rate of negative MRD and prolonged OS.

CPX-351 has been approved for patients with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). No extensive data are available on measurable residual disease (MRD) and long-term clinical outcome using CPX-351 in AML in real life. We retrospectively collected data from 168 patients in 36 centers in France and Italy who had received 1 or 2 cycles of induction with CPX-351.

Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study.

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph- ALL) has significantly improved patients' prognosis. Within the Campus ALL network, we analyzed the outcome of adult Ph- ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial to compare the real-life data with the study results. We included 421 consecutive patients; median age 42 years.

Harnessing Immune Response in Acute Myeloid Leukemia.

Despite the results achieved with the evolution of conventional chemotherapy and the inclusion of targeted therapies in the treatment of acute myeloid leukemia (AML), survival is still not satisfying, in particular in the setting of relapsed/refractory (R/R) disease or elderly/unfit patients. Among the most innovative therapeutic options, cellular therapy has shown great results in different hematological malignancies such as acute lymphoblastic leukemia and lymphomas, with several products already approved for clinical use. However, despite the great interest in also expanding the application of these new treatments to R/R AML, no product has been approved yet for clinical application.

Multicenter Observational Retrospective Study on Febrile Events in Patients with Acute Myeloid Leukemia Treated with Cpx-351 in "Real-Life": The SEIFEM Experience.

In the present study, we aimed to evaluate the absolute risk of infection in the real-life setting of AML patients treated with CPX-351. The study included all patients with AML from 30 Italian hematology centers of the SEIFEM group who received CPX-351 from July 2018 to June 2021. There were 200 patients included.

Multicenter retrospective analysis of clinical outcome of adult patients with mixed-phenotype acute leukemia treated with acute myeloid leukemia-like or acute lymphoblastic leukemia-like chemotherapy and impact of allogeneic stem cell transplantation: a Campus ALL study.

Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent.

Donor selection for adoptive immunotherapy with NK cells in AML patients: Comparison between analysis of lytic NK cell clones and phenotypical identification of alloreactive NK cell repertoire.

Natural killer (NK) cell-based adoptive immunotherapy in leukemia patients is an emerging field of interest based on clinical evidence of efficacy and safety. Elderly acute myeloid leukemia (AML) patients have been successfully treated with NK cells from HLA-haploidentical donors, especially when high amounts of alloreactive NK cells were infused. The aim of this study was comparing two approaches to define the size of alloreactive NK cells in haploidentical donors for AML patients recruited in two clinical trials with the acronym "NK-AML" (NCT03955848), and "MRD-NK".

CD38-Induced Metabolic Dysfunction Primes Multiple Myeloma Cells for NAD-Lowering Agents.

Cancer cells fuel growth and energy demands by increasing their NAD biosynthesis dependency, which therefore represents an exploitable vulnerability for anti-cancer strategies. CD38 is a NAD-degrading enzyme that has become crucial for anti-MM therapies since anti-CD38 monoclonal antibodies represent the backbone for treatment of newly diagnosed and relapsed multiple myeloma patients. Nevertheless, further steps are needed to enable a full exploitation of these strategies, including deeper insights of the mechanisms by which CD38 promotes tumorigenesis and its metabolic additions that could be selectively targeted by therapeutic strategies.

Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front-line with paediatric-inspired regimens: A retrospective multicentre Campus ALL study.

Within the Campus ALL network we analyzed the incidence, characteristics, treatment and outcome of a central nervous system (CNS) relapse in 1035 consecutive adult acute lymphoblastic leukemia (ALL) patients treated frontline with pediatric-inspired protocols between 2009 and 2020. Seventy-one patients (6.8%) experienced a CNS recurrence, more frequently in T- (28/278; 10%) than in B-ALL (43/757; 5.

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells.

Immune checkpoint inhibitors (CI) have demonstrated clinical activity in Hodgkin Lymphoma (HL) patients relapsing after autologous stem cell transplantation (ASCT), although only 20% complete response (CR) rate was observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI).