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Non\u2010invasive serum sampling provides an opportunity for sustainable repetitive sampling of patients, which allows for more frequent evaluation of the biological response and enhanced flexibility in treatment selection in contrast to tissue biopsies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To pin\u2010point biologically relevant changes in pre\u2010 and on\u2010treatment serum proteome samples in relapsed mantle cell lymphoma (MCL) patients, leading to insight into mechanisms behind response to treatment in sub\u2010groups of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pre\u2010 and on\u2010treatment serum samples from relapsed MCL patients treated with a triple combination therapy of rituximab, ibrutinib and lenalidomide were available for the study, together with detailed clinicopathological information. A microarray technology targeting 158 serum proteins using 371 antibody\u2010fragments was used to compare the serum proteome at the two time\u2010points.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Proteins modulated by the treatment were shown to be associated to a MCL sub\u2010group with <jats:italic>ATM\/TP53<\/jats:italic> alterations, which emphasizes the importance of treatment stratification. Absolute values of serum protein levels in on\u2010treatment samples were highly variable and showed no correlation to outcome. To circumvent the challenge of variability in absolute serum protein levels, the velocity of change of individual serum proteins was used to identify proteins associated with clinical response. Increased values of TGF\u2010\u03b21, CD40 and complement component 4 comparing pre\u2010 and on\u2010treatment samples were associated with remaining minimal residual disease (MRD) and increased BTK was associated with short progression\u2010free survival (PFS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We show that the genetic sub\u2010type of MCL affects the biological response to treatment in serum and that the change in defined serum proteins reveals the biology associated with clinical response.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.1524","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T12:19:55Z","timestamp":1627474795000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum proteome modulations upon treatment provides biological insight on response to treatment in relapsed mantle cell 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