Clinical Impact of a Common PDCD1 Germline Variant in DLBCL Patients Treated with CAR-T Cell Therapy

Chimeric antigen receptor CAR T-cells are effective immunotherapies for patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) with overall response rates of 63-84% and complete response rates of 43-54%. Programmed cell death protein 1 (PD-1) is a cell surface receptor with immune check-point function. There are several common germline variants of the PDCD1 gene, including the linked single nucleotide polymorphisms (SNP) rs6710479 and rs2227981. Genetic variants of the immune-checkpoint regulator PDCD1 gene may affect clinical responses to CAR-T cell therapy. In this retrospective single-center study, we assessed the prevalence and outcomes of the PDCD1 gene variants rs6710479 and rs2227981 in r/r DLBCL patients undergoing CAR-T cell therapy. The linked SNP's were prevalent in 68% of the studied DLBCL patients (CT-AG and TT-AA). In a retrospective comparative analysis, we observed differences in clinical outcomes in PDCD1 CC-GG versus CT-AG and TT-AA carriers with one-year PFS rates of 80% versus 50% and 48% (p = 0.01), and two-year OS rates of 74% versus 55% and 33%, respectively (p = 0.001). In conclusion, common PDCD1 germline variants may have influenced the treatment outcomes in FMC63-anti-CD19 CAR-T cell therapy, and the PDCD1 major allele (CC-GG) may associate with a favorable response.