Page 64 - Haematologica Vol. 110 - January 2025

ARTICLE - Real-life study on 421 adult Ph-neg ALL treated with LAL1913 program D. Lazzarotto et al.
Sacro Cuore, Roma; 34Dipartimento di Medicina, Università degli Studi di Udine, Udine; 35Hematology Unit, Santa Maria di Ca’ Foncello Hospital, Treviso; 36S.C. Ematologia, Ospedale S.G. Moscati, Taranto; 37Haematology, Department of Medicine, Ospedale St. Eugenio, Roma; 38Hematology, Hospital “Antonio Cardarelli”, Napoli; 39UO Ematologia, Dipartimento di Medicine Specialistiche, Azienda Ospedaliero-Universitaria Arcispedale S. Anna, Ferrara; 40Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, Orbassano; 41SCDU Ematologia e Terapie Cellulari, AO Ordine Mauriziano, Torino; 42UCO Ematologia, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste; 43ASST Grande Ospedale Metropolitano Niguarda, Milano and 44Centro Dati Fondazione GIMEMA Franco Mandelli, Roma, Italy
Abstract
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 pa- tients 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. The complete remission (CR) rate after the first course of chemotherapy was 94%, and measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a mul- tivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high-risk (VHR) and MRD positive cases, transplanted (hematopoietic stem cell transplantation [HSCT]) patients had a significantly better DFS than non-HSCT patients (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs. 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large, real-life cohort of Ph- ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial (CR rate after C1, 94% vs. 85%, P=0.0004; 3-year OS, 67% vs. 67%, P=0.94; 3-year DFS, 57% vs. 63%, P=0.17). HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.
Introduction
tients with Ph- ALL treated outside the clinical trial, in a real-life setting.
Methods
Patients and objectives of the study
We included 421 consecutive adult patients with newly diagnosed Ph- ALL or lymphoblastic lymphoma (LL, with <20% bone marrow blasts) treated according to the GIMEMA LAL1913 protocol,1 outside the clinical trial, between Sep- tember 2016 and December 2022. The data were collected from 39 hematology centers that are part of the Campus ALL network in Italy.
The main objectives of the study were to compare the complete remission (CR) rate, the overall survival (OS), and the disease-free survival (DFS) between the real-life cohort (421 cases) and the GIMEMA LAL1913 clinical trial population (203 cases). Secondary endpoints included evaluation of the treatment toxicity and the allogeneic stem cell transplan- tation (HSCT) rate according to the risk-group at diagnosis. Diagnostic procedures such as immunophenotyping, cy- togenetics and molecular studies were carried out ac- cording to the GIMEMA LAL1913 protocol indications.1,2 The Philadelphia-like signature was not routinely tested in this real-life population. In line with the GIMEMA LAL1913 trial, 3 risk classes were defined at diagnosis (as reported in the Online Supplementary Appendix).
There is still no definitive consensus on the optimal treat- ment regimen for adult Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) to optimally balance efficacy and toxicity, as shown by the different treatment backbones employed by cooperative study groups.1-7 None- theless, over recent years, numerous phase II and phase III clinical trials from different countries have been associated with better results compared to those from previous expe- riences.1-7 These improvements have been achieved using intensive pediatric-inspired protocols, new formulations of asparaginase, and revised stratification models which included measurable residual disease (MRD) monitoring, in addition to baseline risk factors.8-10 However, data on the real-life applicability of therapeutic regimens tested in clinical trials, which inherently enroll selected patient populations, are very limited.
Recently, the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) published the results of the LAL1913 clinical trial, which included 203 homogeneously treated adult Ph- ALL patients with a pediatric-inspired protocol.1 After the completion of this study, most Italian hematol- ogy centers used the same therapeutic program in their clinical practice while the new protocol for Ph- ALL was under discussion. In this paper, we report the efficacy and safety data of a chemotherapy program performed according to the GIMEMA LAL1913 protocol in adult pa-
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