Page 121 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

SDIRSACR Oncology Insights

Material and Methods: Twenty-one BRAF wild type MM patients were included in the study. TGFB1 and IFNG gene
expression was quantified using TaqMan qPCR after total RNA isolation from peripheral blood mononuclear cells. Fold
changes (FC) were calculated using the ddCt method with GAPDH as the reference gene. Expression was measured at
baseline and before the 5th, 9th, 13th, and 17th cycles of immunotherapy. Patients were classified into the progression
group (PG) (n=10) or non-progression group (NPG) (n=11) based on outcomes within one year. Baseline levels (BL) of
TGFB1, IFNG, LDH, CRP, neutrophils (NEU), lymphocytes (LY), and NEU/LY ratio (N/L), were compared between groups
using the Mann-Whitney test. Time to progression (TTP) was analyzed with Kaplan–Meier survival methods, and group
differences were tested with the log-rank test. In TTP analysis, patients were divided into low or high expression group
using median FC value of TGFB1 and IFNG. In NPG, longitudinal changes in cytokine gene expression were assessed
with the Friedman test. In PG, TGFB1 and IFNG values at BL were compared with values at the time of progression
using the Mann-Whitney test. Correlations between LDH, CRP, NEU, LY, N/L and TGFB1 and IFNG were tested with
Spearman’s rank correlation.
Results: There were no significant differences in TGFB1, IFNG, LDH, CRP, NEU, LY, N/L at BL between PG and NPG, but
TGFB1 showed a trend toward lower values in PG (p=0.053). Log-rank analysis showed no significant link between
cytokine gene expression at BL and disease progression, but lower values of TGFB1 trended toward shorter TTP
(p=0.090). There was no correlation between LDH, CRP, NEU, LY, N/L and TGFB1 or IFNG expression. No significant
differences existed in TGFB1 or IFNG levels over time in NPG, nor between BL and levels at the time of progression in
PG.
Conclusions: In this cohort of MM patients treated with Pembrolizumab, lower BL TGFB1 indicated a trend towards
shorter TTP and higher probability of progression. These findings suggest the predictive potential of TGFB1 that requires
larger studies

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