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Letters to the Editor
was 25.7 mo (95% CI: 16.7-42.2) for POM versus 17.4 mo (95% CI: 12.5-NA) for POM-LoDEX (log-rank P=0.356; HR: 1.36, 95%CI: 0.70-2.64) (Figure 1B).
There was no difference in NK populations observed between responders and non-responders at baseline. However, in responders, (i) inhibited NK cells (CD3- CD19-CD56+CD159a+CD158a+) were enriched at baseline and significantly decreased following induction (pooled maintenance timpepoints) (P<0.0001), and (ii) activated NK cells (CD3-CD19-CD56+CD337+CD336+, no inhibitory receptors) were significantly increased fol- lowing induction (pooled maintenance time points) (P<0.0001) (Figure 2A). Following commencement of maintenance, there was no emergent difference in NK populations observed between treatment arms. There was no difference observed in NK-cell populations according to maintenance arm at baseline and at mainte- nance (C6D1) (primary objective).
There was no difference in Treg percentage (Treg%) between responders and non-responders at baseline. After induction and prior to commencing maintenance (C1D1 timepoint), responders demonstrated a depletion of Treg% (P<0.0001). Following commencement of maintenance, Treg depletion was maintained in patients who continued on POM-LoDEX, whereas POM patients who had LoDEX withdrawn demonstrated a partial
recovery in Treg% (P<0.05). (Figure 2B).
Unsupervised analysis (all patients) at baseline defined
131 immune cell populations (Figure 2C): there were no significant differences identified between responders and non-responders. At maintenance (responders), there was enrichment of heterogenous neutrophil populations (pooled maintenance time points). Of the 131 clusters identified at baseline, five of the eight large clusters (each at least 3% [median] of total nucleated cells evaluated) that were significantly enriched (P<0.0001) following POM-LoDEX induction were activated neutrophil popu- lations (all expressed CD66b but with variable expres- sion of CD24/CD16/CD11c/CD11b/CD45RO) (Figure 2D).
Online Supplementary Table S2 lists all grade adverse events (AE). When comparing the mITT population, the incidence of AE was generally similar, including hemato- logic toxicity. Significant differences were observed in the incidence of lung infections (higher in POM-LoDEX, P=0.003) and peripheral sensory neuropathy (higher in POM-LoDEX, P=0.041). Median durations of exposure to maintenance POM were 2.5 mo and 6.2 mo in the POM and POM-LoDEX arms respectively. Dose intensi- ty interquartile ranges were similar in both arms from maintenance C1D1 through to C6D1. Online Supplementary Figure S1 shows results for survival post-
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