ADCs, BiTEs, CARs, and Small Molecules: A New Era of Targeted Therapy in Non-Hodgkin Lymphoma


Abramson JS, et al. Am Soc Clin Oncol Educ Book 2020.


Novel immunotherapies and small molecular inhibitors are transforming our approach to previously treated and newly diagnosed patients across the spectrum of non-Hodgkin lymphomas (NHLs). Anti-CD19 CAR T cells are now indicated for the treatment of relapsed/refractory aggressive B-cell lymphomas after at least two previous lines of therapy in which durable remissions are achieved in approximately 40% of previously incurable patients. Second-line chemoimmunotherapy remains the standard of care at

first relapse, but poor outcomes with conventional treatment in this setting creates an appealing rationale for earlier use of CAR T cells, which is currently under investigation, along with even earlier use in selected high-risk patients in the frontline setting. Other emerging immunotherapies include antibody-drug conjugates (ADCs), such as polatuzumab vedotin for multiple-relapsed diffuse large B-cell lymphoma (DLBCL) in combination with bendamustine-rituximab. Multiple bispecific antibodies that bring malignant B cells in contact with effector T cells appear promising in early clinical trials and will likely emerge as off-the-shelf immunotherapy options. Chemotherapy-free small molecule-based regimens are increasingly available for mantle cell (MCLs) and follicular lymphomas (FLs). Bruton tyrosine kinase inhibitors (BTKi) now represent standard second-line therapy for MCL and are being investigated in combination and as initial therapy. Lenalidomide-rituximab is an active regimen in both FL and MCL and may be used in either relapsed/refractory or previously untreated disease. Three PI3K inhibitors are approved for multiple-relapsed FL and can induce durable remissions in patients with chemotherapy- and rituximab-refractory disease. Additional emerging targeted therapies include BCL2 inhibition in MCL and EZH2 inhibition in FL.