Early peripheral clearance of leukemia-associated immunophenotypes in AML: centralized analysis of a randomized trial

Although genetics is a relevant risk factor in acute myeloid leukemia (AML), it can be minimally informative and/or not readily available for the early identification of patients at risk for treatment failure. In a randomized trial comparing standard vs high-dose induction (ClinicalTrials.gov 64NCT00495287), we studied early peripheral blast cell clearance (PBC) as a rapid predictive assay of chemotherapy response to determine whether it correlates with the achievement of complete remission (CR), as well as postremission outcome, according to induction intensity. Individual leukemia-associated immunophenotypes (LAIPs) identified pretherapy by flow cytometry were validated and quantified centrally after 3 days of treatment, expressing PBC on a logarithmic scale as the ratio of absolute LAIP1 cells on day 1 and day 4. Of 178 patients, 151 (84.8%) were evaluable. Patients in CR exhibited significantly higher median PBC (2.3 log) compared with chemoresistant patients (1.0 log; P<.0001). PBC<1.0 predicted the worst outcome (CR, 28%). With 1.5 log established as the most accurate cutoff predicting CR, 87.5% of patients with PBC .1.5 (PBChigh, n = 96) and 43.6% of patients with PBC 641.5 (PBClow, n = 55) achieved CR after single-course induction (P<.0001). CR and PBChigh rates were increased in patients randomized to the high-dose induction arm (P 5 .04) and correlated strongly with genetic/cytogenetic risk. In multivariate analysis, PBC retained significant predictive power for CR, relapse risk, and survival. Thus, PBC analysis can provide a very early prediction of outcome, correlates with treatment intensity and disease subset, and may support studies of customized AML therapy

Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19

Immunotherapy approaches to treat adult acute lymphoblastic leukemia

Recent developments in immunotherapy are improving treatment results of B-precursor acute lymphoblastic leukemia. This advancement is promoted by new monoclonal antibodies such as inotuzumab ozogamicin, ofatumumab and blinatumomab, by rituximab, and by genetically engineered chimeric antigen receptor-modified T-cells. These treatments, variously targeting CD22, CD20 and CD19 antigens, yield unprecedented high rates of hematologic and molecular remissions even when used in monotherapy and in chemo-resistant or post-transplantation relapsed patients. Beside the encouraging results in relapsed/refractory disease, these agents may open a totally new era in the frontline management of this illness, redefining treatment standards and options for different risk subsets and placing the achievement of a molecular remission at the forefront of treatment objectives. The ever increasing importance of modern immunotherapy in improving treatment design and therapeutic outcome is reviewed

MODERN IMMUNOTHERAPY OF ADULT B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA WITH MONOCLONAL ANTIBODIES AND CHIMERIC ANTIGEN RECEPTOR MODIFIED T CELLS

The introduction of newer cytotoxic monoclonal antibodies and the chimeric antigen receptor-modified T-cells is opening a new age in the management of B-lineage adult acute lymphoblastic leukemia. This therapeutic change must be very positively acknowledged because of the limits of intensive chemotherapy programs and allogeneic stem cell transplantation. With these traditional therapeutic tools in fact cure can be achieve in only 40-50% of the patients, with higher failure rates in the elderly, in those with post-induction persistence of minimal residual disease and especially in refractory/relapsed disease. The place of the novel immunotherapeutics in improving the outcome of adult patients with B-lineage acute lymphoblastic leukemia is reviewed

PROGNOSTIC SIGNIFICANCE AND TREATMENT IMPLICATIONS OF MINIMAL RESIDUAL DISEASE STUDIES IN PHILADELPHIA-NEGATIVE ADULT ACUTE LYMPHOBLASTIC LEUKEMIA

Acute lymphoblastic leukemia (ALL) is curable in about 40-50% of adult patients, however this is subject to ample variations owing to several host- and disease-related prognostic characteristics. Currently, the study of minimal residual disease (MRD) following induction and early consolidation therapy stands out as the most sensitive individual prognostic marker to define the risk of relapse following the achievement of remission, and ultimately that of treatment failure or success. Because substantial therapeutic advancement is now being achieved using intensified pediatric-type regimens, MRD analysis is especially useful to orientate stem cell transplantation choices. These strategic innovations are progressively leading to greater than 50% cure rates

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-negative acute lymphoblastic leukemia/lymphoma (Ph- ALL/LL). The GIMEMA LAL1913 trial tested a modified regimen adding pegaspargase 2000 IU/m2 to courses 1, 2, 5 and 6 of an eight-block protocol for patients 18-65 years, with dose reductions in patients >55 years. Responders were risk-stratified to allogeneic hematopoietic stem cell transplantation (HCT) or maintenance according to clinical characteristics and minimal residual disease (MRD). Out of 203 study patients (median age 39.8 years, 68.5% B-lineage), 185 (91%) achieved a complete remission (CR). The 3-year overall survival (OS), event-free (EFS) and disease-free (DFS) survival rates were 66.7% (95% confidence intervals, 64.4-60.1%), 57.7% (51.0-65.3%) and 63.3% (56.3-71.1%), respectively, fulfilling the primary study endpoint of a 2-year DFS >55%. While by intention-to-treat DFS was 74% and 50% in the chemotherapy (n=94) and HCT (n=91) assigment cohorts, a time-dependent analysis proved the value of HCT in eligible patients (DFS HCT 70% vs. no HCT 26%, P<0.0001). In multivariate analysis, age and MRD (n=151) were independent prognostic factors associated with DFS rates of 86% (age less/equal to 40/MRD-negative, n=66), 65% (age >40/MRD-negative, n=48), 64% (age less/equal to 40/MRD-positive, n=17) and 25% (age >40/MRD-positive, n=20) (P<0.0001). Grade 2/greater pegaspargase toxicity was mainly observed at course 1 (41 episodes in 32 patients), contributing to induction death in 2 patients, but was rare and milder thereafter. This pegarspargase-containing risk-oriented program was feasible and improved outcome of Ph- ALL/LL patients up to 65 years in a multicenter national setting. ClinicalTrials.gov #NCT02067143