: 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.

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 Paola; Messina, Monica; Elia, Loredana; De Propris, Maria Stefania Stefania; Scattolin, Anna Maria; Audisio, Ernesta; Marbello, Laura; Borlenghi, Erika; Zappasodi, Patrizia; Mauro, Elisa; Martinelli, Giovanni; Mattei, Daniele; Fracchiolla, Nicola Stefano; Bocchia, Monica; De Fabritiis, Paolo; Bonifacio, Massimiliano; Candoni, Anna; Cassibba, Vincenzo; Di Bartolomeo, Paolo; Latte, Giancarlo; Trappolini, Silvia; Guarini, Anna Rita; 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

Candoni, Anna;
2023

Abstract

: 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.
2023
7
16
4448
4461
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 Paola; Messina, Monica; Elia, Loredana; De Propris, Maria Stefania Stefania; Scattolin, Anna Maria; Audisio, Ernesta; Marbello, Laura; Borlenghi, Erika; Zappasodi, Patrizia; Mauro, Elisa; Martinelli, Giovanni; Mattei, Daniele; Fracchiolla, Nicola Stefano; Bocchia, Monica; De Fabritiis, Paolo; Bonifacio, Massimiliano; Candoni, Anna; Cassibba, Vincenzo; Di Bartolomeo, Paolo; Latte, Giancarlo; Trappolini, Silvia; Guarini, Anna Rita; 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]
Bassan, Renato; Chiaretti, Sabina; Della Starza, Irene; Spinelli, Orietta; Santoro, Alessandra; Paoloni, Francesca Paola; Messina, Monica; Elia, Lored...espandi
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