Figure 3.
Modakafusp alfa binds to CD38 and induces type 1 interferon pathway activation in the peripheral blood of patients with R/R MM. Line graphs (mean ± standard deviation) and box and whisker plots (whiskers 10-90 percentile) depict the percent of CD38 receptors on viable leukocytes occupied by modakafusp alfa (A); the fold change in the type 1 interferon gene signature score, as defined by the average fragments per kilobase of exon per million mapped fragments (FPKM) of 25 interferon-stimulated genes (B); the fold change in CD38 receptor density on NK cells, T cells, and myeloma cells (defined as viable leukocytes that are CD138+ SSC-mid CD19− CD20−) (C); the percentage of activated NK cells and CD8 T cells, as defined by CD69 expression (D); and serum concentration of MCP-2 (E) for peripheral blood samples collected during C1. Baseline for all data sets is defined as C1D1 predose. C1D15 statistical evaluations did not include patients dosed on the modified QW schedule (0.001, 0.01, and 0.1 mg/kg dose levels) because of an increased number of doses administered before C1D15 compared with other schedules. Statistical evaluations were not conducted for C1D3 and C1D8 because of limited sample numbers nor C2D1 predose because of the varying cycle lengths and dosing frequency. A linear regression model was used to evaluate the trend DR. Wilcoxon signed rank test was used to determine whether pooled data from all doses, except at C1D15 as noted, per time point were significantly changed from baseline. A significant ΔBL was defined as a fold change of ≥1.5 above, or ≤2/3 below, baseline for cellular markers (panels A,C,D); similarly, for gene expression and cytokines (panels B,E), a significant ΔBL was defined as a fold change ≥2 or ≤1/2. The ΔBL thresholds for CD38 density changes are shaded in gray on panel C. DR and ΔBL P values are depicted above data sets. If there was no significant DR P value, data was collapsed by time point. Statistical analysis findings for panel C can be found in supplemental Figure 5B-D. ΔBL, change from baseline; C, cycle; D, day; DR, dose responsiveness; IFN, interferon; MCP-2, monocyte chemotactic protein-2; MdFI, median fluorescence intensity; n.s., nonsignificant result; QW, once weekly; SSC, side scatter.

Modakafusp alfa binds to CD38 and induces type 1 interferon pathway activation in the peripheral blood of patients with R/R MM. Line graphs (mean ± standard deviation) and box and whisker plots (whiskers 10-90 percentile) depict the percent of CD38 receptors on viable leukocytes occupied by modakafusp alfa (A); the fold change in the type 1 interferon gene signature score, as defined by the average fragments per kilobase of exon per million mapped fragments (FPKM) of 25 interferon-stimulated genes (B); the fold change in CD38 receptor density on NK cells, T cells, and myeloma cells (defined as viable leukocytes that are CD138+ SSC-mid CD19− CD20−) (C); the percentage of activated NK cells and CD8 T cells, as defined by CD69 expression (D); and serum concentration of MCP-2 (E) for peripheral blood samples collected during C1. Baseline for all data sets is defined as C1D1 predose. C1D15 statistical evaluations did not include patients dosed on the modified QW schedule (0.001, 0.01, and 0.1 mg/kg dose levels) because of an increased number of doses administered before C1D15 compared with other schedules. Statistical evaluations were not conducted for C1D3 and C1D8 because of limited sample numbers nor C2D1 predose because of the varying cycle lengths and dosing frequency. A linear regression model was used to evaluate the trend DR. Wilcoxon signed rank test was used to determine whether pooled data from all doses, except at C1D15 as noted, per time point were significantly changed from baseline. A significant ΔBL was defined as a fold change of ≥1.5 above, or ≤2/3 below, baseline for cellular markers (panels A,C,D); similarly, for gene expression and cytokines (panels B,E), a significant ΔBL was defined as a fold change ≥2 or ≤1/2. The ΔBL thresholds for CD38 density changes are shaded in gray on panel C. DR and ΔBL P values are depicted above data sets. If there was no significant DR P value, data was collapsed by time point. Statistical analysis findings for panel C can be found in supplemental Figure 5B-D. ΔBL, change from baseline; C, cycle; D, day; DR, dose responsiveness; IFN, interferon; MCP-2, monocyte chemotactic protein-2; MdFI, median fluorescence intensity; n.s., nonsignificant result; QW, once weekly; SSC, side scatter.

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