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). Of 203 study patients (median age, 39.8 years), 91% achieved a complete remission. The 3-year overall survival, event-free, and disease-free survival (DFS) rates were 66.7%, 57.7%, and 63.3%, respectively, fulfilling the primary study end point of a 2-year DFS >55%. Although based on the intention-to-treat, the DFS being 74% and 50% in the chemotherapy (n = 94) and HCT (n = 91) assignment cohorts, respectively, a time-dependent analysis proved the value of HCT in patients who were eligible (DFS HCT 70% vs no HCT 26%; P <.0001). In multivariate analysis, age and MRD were independent factors predicting DFS rates of 86% (age < 40 and MRD-negative), 64%-65% (MRD-positive or age > 40) and 25% (age > 40 and MRD-positive); P < .0001. Grade & GE;2 pegaspargase toxicity was mainly observed at course 1, contributing to induction death in 2 patients but was rare thereafter. This program improved outcomes of patients with Ph- ALL/LL aged up to 65 years in a multicenter national setting. This trial was registered at www.clinicaltrials.gov as #NCT02067143.
Pegaspargase-modified risk-oriented program for adult acute lymphoblastic leukemia: results of the GIMEMA LAL1913 trial / Bassan, Renato; Chiaretti, Sabina; Della Starza, Irene; Spinelli, Orietta; Santoro, Alessandra; Paoloni, Francesca; Messina, Monica; Elia, Loredana; De Propris, Maria Stefania; Scattolin, Anna Maria; Audisio, Ernesta; Marbello, Laura; Borlenghi, Erika; Zappasodi, Patrizia; Mauro, Elisa; Martinelli, Giovanni; Mattei, Daniele; Fracchiolla, Nicola; Bocchia, Monica; De Fabritiis, Paolo; Bonifacio, Massimiliano; Candoni, Anna; Cassibba, Vincenzo; Di Bartolomeo, Paolo; Latte, Giancarlo; Trappolini, Silvia; Guarini, Anna; Vitale, Antonella; Fazi, Paola; Piciocchi, Alfonso; Rambaldi, Alessandro; Foà, Robin. - In: BLOOD ADVANCES. - ISSN 2473-9529. - 7:16(2023), pp. 4448-4461. [10.1182/bloodadvances.2022009596]
Pegaspargase-modified risk-oriented program for adult acute lymphoblastic leukemia: results of the GIMEMA LAL1913 trial
Chiaretti, Sabina;Foà, Robin
2023
Abstract
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). Of 203 study patients (median age, 39.8 years), 91% achieved a complete remission. The 3-year overall survival, event-free, and disease-free survival (DFS) rates were 66.7%, 57.7%, and 63.3%, respectively, fulfilling the primary study end point of a 2-year DFS >55%. Although based on the intention-to-treat, the DFS being 74% and 50% in the chemotherapy (n = 94) and HCT (n = 91) assignment cohorts, respectively, a time-dependent analysis proved the value of HCT in patients who were eligible (DFS HCT 70% vs no HCT 26%; P <.0001). In multivariate analysis, age and MRD were independent factors predicting DFS rates of 86% (age < 40 and MRD-negative), 64%-65% (MRD-positive or age > 40) and 25% (age > 40 and MRD-positive); P < .0001. Grade & GE;2 pegaspargase toxicity was mainly observed at course 1, contributing to induction death in 2 patients but was rare thereafter. This program improved outcomes of patients with Ph- ALL/LL aged up to 65 years in a multicenter national setting. This trial was registered at www.clinicaltrials.gov as #NCT02067143.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
