Plasma Metabolomics During Chemotherapy Desensitization: A Pilot Study

Rapid drug desensitization permits continued chemotherapy, but no validated blood measurement predicts breakthrough reactions during desensitization.

To compare paired plasma metabolomic and lipidomic changes during chemotherapy desensitization with those in tolerant controls, and to describe breakthrough and omalizumab encounters.

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.

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).

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.

What is already known about this topic?: Desensitization lets most patients with carboplatin or paclitaxel hypersensitivity continue treatment. Breakthrough reactions occur, and no validated blood measurement predicts them.What does this article add to our knowledge?: In 14 patients, plasma profiling detected premedication signals before infusion and broad pre-to-post changes; no feature distinguished allergic from control changes at a 5% false discovery rate. Histamine did not consistently rise with breakthrough reactions.How does this study impact current management guidelines?: Biomarker studies during chemotherapy desensitization should match comparators for premedication, time blood draws to symptom onset, and standardize specimen processing; these exploratory findings do not change current desensitization practice.