Plasma Metabolomics During Chemotherapy Desensitization: A Pilot Study

Background: Rapid drug desensitization permits continued chemotherapy, but no validated blood measurement predicts breakthrough reactions during desensitization. Objective: To compare paired plasma metabolomic and lipidomic changes during chemotherapy desensitization with those in tolerant controls, and to describe breakthrough and omalizumab encounters. Methods: In this pilot study, 10 patients undergoing carboplatin or paclitaxel desensitization and four tolerant controls receiving standard infusions contributed 76 draws across 39 encounters (37 with paired pre- and post-infusion draws). Untargeted liquid chromatography-mass spectrometry in four modes yielded 8,646 quality-filtered features (instrument signals). Exact permutation with false discovery rate control compared patient-averaged paired changes from 27 allergic encounters (10 patients) off omalizumab with four control encounters (four patients). Breakthrough and omalizumab comparisons were descriptive. Results: Allergic patients' profiles changed from pre- to post-infusion in three of four modes (Holm-adjusted P = .04). Pre-infusion profiles differed between allergic patients and controls in one mode (Holm-adjusted P = .02). Montelukast, a premedication drug, had the smallest P value among annotated pre-infusion differences and was detected in all 33 allergic and no control pre-infusion draws. No feature distinguished allergic from control paired changes at a 5% false discovery rate. Histamine did not consistently increase in seven paired breakthrough encounters (five patients). Hemolysis was more frequent in allergic post-infusion than pre-infusion draws (16 of 35 vs eight of 33). Conclusion: Profiling during desensitization detected premedication exposure and broad pre-to-post changes largely shared with controls, but no allergy-specific signature. Prospective studies need sampling timed to reactions and medications, comparators matched for premedication and infusion duration, and standardized specimen handling.