Quantitative ex vivo assessment of chemotherapy synergy using patient-derived non-Hodgkin lymphoma samples

초록

Combination chemotherapy is the standard of care for non-Hodgkin lymphoma (NHL), yet clinical outcomes vary and methods for assessing drug interactions in patient-derived samples remain limited. In this study, we explored the association between ex vivo drug sensitivity, pairwise drug synergy metrics, and treatment outcomes in NHL patients receiving CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-based regimens. Tumor biopsy samples from 31 patients were analyzed for sensitivity to the four cytotoxic CHOP agents and selected targeted therapies. Synergy was quantified using multiple models, including Bliss, Loewe, zero interaction potency, highest single agent, quadratic phenotypic optimization platform, and the combination sensitivity score (CSS). Ex vivo sensitivity to vincristine showed the strongest association with treatment response among single agents, whereas prednisone sensitivity showed weaker association. When considering drug pairs, CSS values revealed stronger associations with treatment outcome than single-drug metrics, with certain pairs exhibiting notable differences between responders and non-responders. In contrast, pairs involving prednisone were less informative. Subtype-specific analyses suggested greater inter-patient variability in synergy within aggressive NHL compared to indolent disease. These findings highlight the potential of pairwise synergy assessment as an investigational framework for studying treatment response in NHL. While limited by sample size, this proof-of-concept analysis provides a basis for future studies aimed at validating synergy metrics as complementary tools in therapy optimization and drug development.

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