Checkpoint Inhibition Followed by CAR-T Cell Therapy in Refractory PMLBCL: Immunologic Response and Fertility Preservation in a Young Patient

Primary mediastinal large B-cell lymphoma (PMLBCL) is an aggressive B-cell malignancy that may exhibit resistance to standard chemoimmunotherapy. Novel immunotherapeutic strategies, including checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapy, are being explored in cases that are refractory to treatment. We report the case of a 29-year-old patient with refractory PMLBCL who was treated with pembrolizumab as a bridging therapy followed by axicabtagene ciloleucel (CAR-T) after failing R-CHOP and R-DHAP regimens. Initial disease progression following pembrolizumab was consistent with an immune-related flare phenomenon. Subsequent CAR-T infusion led to a complete metabolic response. Immunologic monitoring revealed expansion of CD3<sup>+</sup> and CD56<sup>+</sup> lymphocyte subsets, suggesting immune activation. Notably, the patient maintained normal endocrine function and conceived spontaneously three years post-treatment, delivering a healthy infant at term. This case highlights the potential synergy between checkpoint inhibition and CAR-T cell therapy in refractory PMLBCL, providing rare evidence of preserved fertility following intensive immunotherapy. Early recognition of immune flare and multidisciplinary management are critical in optimizing outcomes for young patients receiving novel immunotherapeutic approaches.