Paulovich - IO2 immunoMRM panel

Correlative study using immuno-MRM in the Cancer Immunotherapy Trials Network (CITN-10) phase 2 clinical trial of pembrolizumab for the treatment of refractory or relapsed Mycosis fungoides (MF) and Sezary syndrome (SS)
  • Organism: Homo sapiens
  • Instrument: QTRAP 5500
  • SpikeIn: No
  • Keywords: immunotherapy, MRM, enrichment, correlative biomarkers
  • Lab head: Jeff Whiteaker Submitter: Jeff Whiteaker
MF and SS are common subtypes of cutaneous T-cell lymphomas with poor response rates to systemic therapies. Treatments targeting immune checkpoint molecules, like PD-1, have been associated with 15-38% overall response rates in the MF type T-cell lymphomas (Lesokhin et al., 2016; Khodadoust et al., 2020). Thus, correlative, predictive markers of response to identify patients most likely to respond to targeted therapy would be highly beneficial. Using a linear mixed effects regression model, we identified ten peptides with significant abundance changes (adjusted p-value <0.05) in plasma and serum across the pre-treatment (Pre), cycle-2 (C02), and end-of-treatment (EOT) time points. Two peptides, corresponding to IL6R and MST1, respectively, showed significant differences between the response classes.
Experiment Description
A total of 134 samples collected from 24 patients were analyzed, consisting of matched serum (n=67) and plasma (n=67) from three time points (pre-treatment, cycle-2, and end of treatment), enabling a comparison of assay results between the two biospecimen types. Each sample was sequentially processed using the IO-1 and IO-2 multiplexed assays, using separate 100 ┬ÁL aliquots of plasma and serum. Overall, 76/100 peptides corresponding to 72 proteins were detected above the LLOQ in plasma and serum. For analysis of correlative biomarkers, we combined results from IO-1 and IO-2 panels. We applied log2 transformation of the peak area ratio values and filtered out 39 peptides that had missing values (i.e., below LLOQ) in more than 105 samples. Additionally, 4 samples that had missing values in more than 70 peptides were removed. Remaining missing values in the data were imputed with LLOQ/3. Peak area ratios for each peptide were normalized to have mean = 0 and standard deviation = 1 for input to the following linear mixed-effect regression model: Log peak ratio ~ time + plasma/serum + response category (CR/PR or SD/PD) + 1/Subject; where CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease. Three time-points were considered: Pre-Treatment (Pre), Cycle 2 (C02), and End of Treatment (EOT).
Created on 2/17/23, 9:56 AM
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