CD19-targeted immunotherapies for treatment of patients with non-Hodgkin B-cell lymphomas.

Naked anti-CD19 mAbs have shown little clinical benefit in B cell lymphomas. Despite unusual toxicity profiles with many anti-CD19 ADCs slowing development, durable remissions in a substantial minority of patients with refractory aggressive lymphomas should encourage continued efforts in this area. Blinatumomab, an anti-CD19 bispecific T cell engager, has shown impressive responses in relapse/refractory diffuse large B cell lymphoma (DLBCL), but is plagued by neurotoxicity issues and the need for continuous infusion. CD19 targeting CAR-T cell therapies are the most promising, with the potential for curing a third of refractory DLBCL patients. There is still much work to be done to address potentially life-threatening cytokine release syndrome and neurotoxicity, an extended production time precluding patients with rapidly progressive disease, and treatment expense. However, if the promise of CAR-T cell technology is confirmed, this will likely change the approach and prognosis for relapse/refractory aggressive lymphoma.