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CD19 CAR T-cell therapy + lenalidomide is a combination regimen that pairs autologous T cells engineered to express a chimeric antigen receptor (CAR) targeting the B-cell surface antigen CD19 with the oral immunomodulatory drug lenalidomide, primarily investigated in relapsed or refractory B‑cell malignancies such as diffuse large B‑cell lymphoma and other non‑Hodgkin lymphomas. CD19-directed CAR T cells recognize CD19 on malignant and normal B cells via an antibody-derived single-chain variable fragment linked to intracellular CD3ζ and costimulatory domains (typically CD28 or 4‑1BB), leading to T‑cell activation, proliferation, cytokine release, and perforin/granzyme-mediated lysis of CD19‑positive cells.[1][8] Lenalidomide exerts complementary antitumor and immunomodulatory effects by enhancing T‑cell and NK‑cell activation, altering cytokine production, inhibiting pro-survival signaling in malignant B cells, and exerting anti‑angiogenic and direct cytotoxic effects. The combination is under clinical investigation as a strategy to augment the potency, persistence, and durability of response of CD19 CAR T cells, particularly in patients with high-risk or refractory B‑cell lymphomas, but it is not an approved fixed-dose combination product.
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