Outcomes: EFS and OS
The 3-year EFS and OS for patients on COG AALL02P2 (n=118) are 64.3±4.5% and 79.6±3.8%, respectively (Figure 2A ). The initial concern for an inferior EFS on AALL02P2 compared to POG 9412 that led to the premature study closure was confirmed with additional follow-up. Compared to late CNS-R B-ALL patients (n=50) on POG 9412, the 3-year EFS for COG AALL02P2 was significantly inferior (64.3±4.5% vs. 79.9±5.8%; p=0.03). Though the interim analysis was focused on EFS, it was noted that the OS rates were not statistically different (79.6±3.8% vs. 85.8±5.1%; p=0.35) (Figures 2B, 2C ).
This intent to treat analysis of 118 patients included 34 (29%) patients who did not receive protocol-directed chemotherapy and CNS radiation. The decision to come off therapy for some patients was related to the amendment and premature closure. Of those patients who came off protocol directed therapy, 11 received radiation, 5 in association with a second relapse (dose and site not captured).
The rate of second relapses was non-significantly higher for NCI HR ALL (16/40; 40%) compared to those with SR ALL (23/75; 31%) (Table 1 ) with 3-year cumulative incidence of relapse rates of 26.7±5.2% and 35.1±7.7% for NCI SR and HR, respectively (p=0.1901) (Supplementary Figure 1).
The EFS differences between COG AALL02P2 and POG 9412 were most notable for patients who were NCI SR at initial diagnosis (Figure 3 ). The 3-year EFS for patients initially classified as HR were similarly poor (p=0.83) for both POG 9412 (58.3±15.4%; n=12) and AALL02P2 (59.9±7.9%). Overall survival rates were also similar (p=0.97) for 9412 and AALL02P2, 66.7±14.6% and 67.2±7.6%, respectively. In both studies, patients initially classified as SR did better than their respective HR counterparts, but the 3-year EFS for SR patients on POG 9412 (86.7±5.6%, n=38) was superior (p=0.0149) to those treated on COG AALL02P2 (65.3±5.5%; n=75). In contrast, 3-year OS rates for the SR patients were not statistically different between 9412 and AALL02P2, 92±15.9% vs 85.3±4.1% (p= 0.29), respectively. Of note, 24% of 9412 patients (12/50) were initially NCI HR compared to 53% (40/115) on AALL02P2. The total number of patients on both trials were small, but this discrepancy likely influenced outcome comparisons between the two