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Obinutuzumab reduces POD24 risk in FL patients
26.5%) (Figure 3D). KM survival plots after the 6-, 12-, and 18-month landmarks showed that the risk of death in patients whose disease progressed was higher the earlier progression occurred (Figure 3A-D). This is also shown by the corresponding mortality rates after progression during the selected time windows (0-6, >6-12, >12-18, and >18- 24 months from randomization) (Table 2); rates during each time window were similar for G-chemo- and R- chemo-treated patients (Online Supplementary Table S10).
Discussion
This analysis of updated data from the GALLIUM study confirmed the findings of prior studies4,10,11 showing that early disease progression in patients with FL is associated with a poor prognosis. The proportion of POD24 patients surviving at two years after the 24-month landmark was 82.4% (although 26% of POD24 patients had died before the 2-year landmark), whereas for the noPOD24 group,
the proportion surviving at this time point was 98.2%. Irrespective of treatment arm, patients who had PD in the 24 months after randomization were also much more like- ly to receive additional lymphoma therapy within three months of progression than patients who had PD later. By all of these measures, we confirm the adverse outlook associated with a POD24 event.
Treatment with G-chemo was associated with a marked reduction in the rate of POD24 events relative to R-chemo and these data therefore support the superiority of the G-chemo regimen seen in the GALLIUM primary analysis.9 Notably, there was little difference in the pro- portion of patients in each treatment arm with PD after the 24-month time point, indicating that, to date, the pro- tective effect of G-chemo against early progression has not been counterbalanced by any increased risk of later progression. With small numbers of deaths in both arms and comparatively short follow up (approximately 3.5 years), it should be noted that, despite a reduced risk of POD24 with G-chemo, we have not yet seen an impact on
Figure 1. Progression-free survival (PFS) and progressive dis- ease or death due to progressive disease (POD) events in the 24 months after randomization (POD24) by treatment arm. The table below the graph shows the number of PFS and POD events occurring in the 24 months post-randomization, along with the risk of these events. n: number; PD: progressive dis- ease; CI: confidence interval; HR: hazard ratio; G-chemo: obinutuzumab plus chemotherapy; R-chemo: rituximab plus chemotherapy. aAll 155 patients had PD. bAt 24 months after randomization, deaths from any cause had occurred in 26 (G- chemo) and 38 (R-chemo) patients.
Table 2. Post-progression mortality rates, stratified by time of progression, in the POD24 group (n=155).
Time of progression, months n
0-6 22
>6-12 58
>12-18 46
>18-24 29
Deaths Reason for death PD Other
18 16 2
27 19 8
9 5 4
2 0 2
Patient–years at risk
22.2
111.6
102.2
52.5
Deaths per 100 patient–years (95%CI)
81.0 (51.2-100)
24.2 (16.6-35.3)
8.8 (4.6-16.9)
3.8 (1.0-15.2)
n: number; CI: confidence interval; PD: progressive disease; POD24: progressive disease or death due to progressive disease events in the 24 months after randomization.
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