Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study

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 patients 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 multivariate 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.

Figure 1.

Overall survival and disease-free survival. (A and B) Overall survival (OS) and disease-free survival (DFS) of the entire study population. (C and D) Overall survival (OS) and disease-free survival (DFS) stratified for age (≤40, 41-55, >55 years). NR: not reached; yrs: years.

Figure 2.

Disease-free survival according to measurable residual disease and allogeneic stem cell transplant. (A) Disease-free survival (DFS) stratified for measurable residual disease (MRD) status. (B) Simon-Makuch plot of DFS of very high-risk (VHR) and/or MRD-positive (MRDpos) patients according to allogeneic stem cell transplant (HSCT).

Figure 3.

Univariate and multivariate analysis. (A) Univariate analysis for overall survival (OS). (B) Univariate analysis for disease-free survival (DFS). (C) Multivariate analysis for OS. (D) Multivariate analysis for DFS. ALL: acute lymphoblastic leukemia; CI: Confidence Interval; CNS: central nervous system; Cyto: cytogenetics; ECOG PS: Eastern Cooperative Oncology Group Performance Status; HR: high risk; LL: lymphoblastic lymphoma; MRD: measurable residual disease; SR: standard risk; VHR: very high risk; WBC: white blood cell.

Figure 4.

Comparison of overall survival (OS) and disease-free survival (DFS) between the study population and the GIMEMA LAL1913 clinical trial population. Overall survival (OS) and disease-free survival (DFS) in the real life study population (RL-LAL1913) (N=421) and the GIMEMA LAL1913 clinical trial population (LAL1913) (N=203).