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.

Pure red cell aplasia due to Parvovirus B19 infection and atezolizumab: case report and literature review.

The benefits of immune checkpoint inhibitor (ICI)-based treatment are tempered by immune-related adverse events (irAEs). However, various aspects of the pathogenesis of these events remain unclear. Here, we report the case of a 69-year-old patient with advanced hepatocellular carcinoma (HCC) developing severe anemia after 15 cycles of atezolizumab/bevacizumab.

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.

Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review.

Menin inhibitors are a class of targeted agents that exemplify how a deeper understanding of leukemia pathogenesis can unify seemingly distinct genetic acute leukemia subgroups under a common therapeutic strategy. In particular, acute leukemia with mutations m) and rearrangements (r) represent the primary targets of this emerging drug class. Acute myeloid leukemia (AML) with m-which accounts for approximately 30% of AML cases and AML or acute lymphoblastic leukemia (ALL) with r-and is present in 5-10% of cases, shares a common pathogenetic mechanism: the aberrant activation of the axis.

Subcutaneous blinatumomab in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: post-hoc safety and activity analysis from a multicentre, single-arm, phase 1/2 trial.

Background: Two doses of subcutaneous blinatumomab in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia were identified as preliminary recommended phase 2 doses, based on the dose-escalation phase of this multicentre single-arm, phase 1/2 trial. Here, we aim to further study the safety, activity, and pharmacokinetics of these doses in all participants who have received them, including those treated in the completed phase 1b expansion part of the study.

Methods: We did a post-hoc analysis of data from patients enrolled in the dose-escalation and dose-expansion phases and in the pharmacokinetic evaluation cohort of this multicentre, single-arm, phase 1/2 study.

Outcomes of allogeneic stem cell transplant in adult Philadelphia negative acute lymphoblastic leukemia patients treated with the pediatric-inspired GIMEMA 1913 protocol. A Campus ALL study.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the best consolidative treatment for high-risk acute lymphoblastic leukemia (ALL). The Campus ALL study group analyzed the clinical outcomes of patients treated in the real-life with the pediatric-inspired and minimal/measurable residual disease (MRD)-oriented GIMEMA LAL1913 protocol who underwent alloHSCT. Key factors impacting on outcomes were MRD and remission status (1 complete remission vs 2 complete remission) at transplant.

Venetoclax and hypomethylating agents in octogenarians and nonagenarians with acute myeloid leukemia.

Venetoclax (VEN) plus a hypomethylating agent (HMA) regimen is the standard of care for older adults with acute myeloid leukemia (AML); however, it is associated with significant myelosuppression and complications, potentially limiting its use in those who are very old. We performed a multicenter retrospective analysis of VEN-HMA treatment in octogenarians and nonagenarians to further understand the tolerability, feasibility, dosing considerations, and clinical efficacy in this unique group. Patients with AML aged ≥80 years who received VEN-HMA between March 2015 and April 2022 were reviewed.

Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study.

The prognosis for relapsed or refractory (R/R) nucleophosmin 1-mutated (NPM1m) acute myeloid leukemia (AML) is poor and represents an urgent unmet medical need. Revumenib, a potent, selective menin inhibitor, was recently approved for the treatment of R/R acute leukemia with a KMT2A translocation in patients aged ≥1 year based on results from the phase 1/2 AUGMENT-101 study. Here, we present results from patients with R/R NPM1m AML enrolled in the phase 2 portion of AUGMENT-101.

The evolving therapeutic revolution in adult acute lymphoblastic leukemia.

The past decade has witnessed remarkable advances in deciphering the pathophysiology of acute lymphoblastic leukemia (ALL) and in developing novel targeted therapies. Basic research and genomic mapping have identified new prognostic biomarkers, targets, and ALL subtypes (e.g.

Patient-reported outcomes in Philadelphia chromosome-positive acute lymphoblastic leukemia patients treated with ponatinib or imatinib: results from the PhALLCON trial.

In the Phase 3 PhALLCON trial (NCT03589326), ponatinib demonstrated superior efficacy and comparable safety profile versus imatinib in adults with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Here we report patient-reported outcomes (PRO) from PhALLCON assessed as exploratory endpoints using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EQ-5D-5L. Primary PRO domains included FACT-G physical well-being, FACT-Leu subscale (FACT-LeuS), Trial Outcome Index (TOI), FACT-Leu total score, FACT-G total score, and EQ-5D visual analogue scale.

The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy.

Patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC) have limited treatment options. The phase 3 ENHANCE-3 study aimed to determine whether magrolimab (magrolimab arm) was superior to placebo (control arm) when either was combined with venetoclax and azacitidine. Adults with previously untreated AML who were ineligible for IC were randomized to receive magrolimab (1 mg/kg on days 1 and 4, 15 mg/kg on day 8, 30 mg/kg on days 11 and 15, then weekly for 5 weeks, and then every 2 weeks) or placebo, venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter), and azacitidine (75 mg/m2 days 1-7) in 28-day cycles.

Quality-Adjusted Time Without Symptoms of Disease or Toxicity (Q-TWiST) in Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Comparison of Ponatinib Versus Imatinib.

Background: In the phase 3 ponatinib-3001 trial (PhALLCON, NCT03589326), ponatinib demonstrated superior efficacy over imatinib with comparable safety in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This post hoc analysis evaluated the net benefits of ponatinib using a quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) approach.

Methods: Overall survival (OS) time for patients from PhALLCON was partitioned into three health states: TOX (time with grade 3+ treatment-emergent adverse events [TEAEs] before disease progression), TWiST (time without toxicity before progression), and REL (time from progression until death or end of follow-up).

Upfront intensive treatment analysis of the Italian Cohort Study on FLT3-mutated AML patients (FLAM): The impact of a FLT3 inhibitor addition to standard chemotherapy in the real-life setting.

Background: The addition of a FLT3 inhibitor (FLT3i) to standard chemotherapy to treat fit newly diagnosed (ND) patients with FLT3-mutated acute myeloid leukemia (AML) represents the standard of care resulting from clinical trial results. However, evidence regarding FLT3i adoption in routine clinical practice is still scarce.

Methods: Clinical data are reported from 394 ND patients with FLT3-mutated AML enrolled in the retrospective observational Italian Cohort Study on FLT3-mutated patients with AML and treated with an upfront intensive regimen with (FLT3i group, n = 92) or without (CT group, n = 302) the addition of a FLT3i.

INO-CD22: A multicenter, real-world study of inotuzumab ozogamicin safety and effectiveness in adult patients with relapsed/refractory acute lymphoblastic leukemia.

Background: Inotuzumab ozogamicin (IO) has helped to change the treatment paradigm in B-cell acute lymphoblastic leukemia (B-ALL) but real-world data are limited.

Methods: The INO-CD22 study is a multicenter retrospective cohort study of adult patients with relapsed/refractory B-ALL treated with IO in 24 Italian centers from 2014 to 2019, with the aim of assessing the response, survival, and toxicity of IO.

Results: Data for 73 eligible patients were obtained: the median age at the start of IO treatment was 52.

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.

Magrolimab plus azacitidine vs physician's choice for untreated TP53-mutated acute myeloid leukemia: the ENHANCE-2 study.

Patients with TP53-mutated acute myeloid leukemia (AML) have an extremely poor prognosis, necessitating new treatments. The global, randomized, phase 3 ENHANCE-2 trial evaluated the anti-CD47 monoclonal antibody magrolimab plus azacitidine (Magro/Aza) for previously untreated TP53-mutated AML. Patients determined ineligible for intensive therapy were randomized to receive Magro/Aza or venetoclax plus Aza (Ven/Aza); those eligible for intensive therapy were randomized to receive Magro/Aza or 7+3 induction chemotherapy.

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.

Azacitidine and venetoclax with or without pevonedistat in patients with newly diagnosed acute myeloid leukemia.

Unlabelled: This phase 2 study investigated pevonedistat + azacitidine + venetoclax ( = 83) versus azacitidine + venetoclax ( = 81) in patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy. The study was stopped early following negative results from PANTHER, which evaluated pevonedistat in higher-risk myelodysplastic syndromes/chronic myelomonocytic leukemia or low-blast AML. Outcomes were analyzed up to the datacut.

Clinical impact of ceftazidime/avibactam on the treatment of suspected or proven infections in a large cohort of patients with haematological malignancies: a multicentre observational real-world study.

Objectives: To evaluate clinical impact of ceftazidime/avibactam on treating infections due to MDR Gram-negative bacteria in patients with haematological malignancies (HMs).

Methods: We conducted a retrospective, observational study at 17 Italian haematological wards that included patients with HMs receiving ceftazidime/avibactam for the treatment of suspected or proven infections. The primary endpoint was all-cause mortality 30 days after infection onset.

Methodology and clinical utility of longitudinal UBA1 tracking in VEXAS syndrome.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) is a haemato-inflammatory syndrome genetically defined by somatic mutations in the X-linked UBA1 gene, typically Val/Thr/Leu substitutions at the Met41 hotspot. Clinical manifestations are heterogeneous and refractory to most haemato-rheumatological treatments. To date, no guidelines exist for the management of VEXAS, and scarce is the evidence on methodology and clinical significance of longitudinal UBA1 clonal burden evaluation upon therapy.

Outcome of adult acute myeloid leukemia patients with extramedullary disease and treatment with venetoclax/ hypomethylating agents.

We evaluated response to venetoclax/hypomethylating agents (HMA) in 46 patients with acute myeloid leukemia (AML) characterized by extramedullary disease. The median age of these patients was 65 years (range, 19-81). The patients had a median of two sites of extramedullary disease (range, 1-5) and 35 (76%) had concurrent bone marrow involvement.