Novel Therapies Potentially Available for Pediatric B-Cell Non-Hodgkin Lymphoma

Authors: Paul D. Harker-Murray MD, PhD1, Lauren Pommert MD, MS1, and Matthew J. Barth MD2
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  • 1 Pediatric Oncology, Midwest Children's Cancer Center, Milwaukee, Wisconsin; and
  • | 2 Roswell Park Cancer Institute, Buffalo, New York.
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Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma are the most common aggressive pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs). Despite excellent survival with current chemotherapy regimens, therapy for Burkitt lymphoma and DLBCL has a high incidence of short- and long-term toxicities. Patients who experience relapse generally have a very poor prognosis. Therefore, novel approaches using targeted therapies to reduce toxicities and improve outcomes in the relapse setting are needed. The addition of rituximab, a monoclonal antibody against CD20, to upfront therapy has improved survival outcomes for high-risk patients and may allow decreased total chemotherapy in those with low-risk disease. Antibody–drug conjugates have been combined with chemotherapy in relapsed/refractory (R/R) NHL, and multiple antibody–drug conjugates are in development. Additionally, bispecific T-cell–engaging antibody constructs and autologous CAR T-cells have been successful in the treatment of R/R acute leukemias and are now being applied to R/R B-NHL with some successes. PD-L1 and PD-L2 on tumor cells can be targeted with checkpoint inhibitors, which restore T-cell–mediated immunity and antitumor responses and can be added to conventional chemotherapy and immune-directed therapies to augment responses. Lastly, trials of small molecule inhibitors targeting cell signaling pathways in NHL subtypes are underway. This article reviews many of the targeted therapies under development that could be considered for future trials in R/R pediatric mature B-NHL.

Submitted March 16, 2020; accepted for publication June 22, 2020.

Disclosures: Dr. Harker-Murray has disclosed that he has received consultant fees from Regeneron Pharmaceuticals. The remaining authors have disclosed that they have no financial interests, arrangements, or affiliations with the manufacturers of any products discussed in this article or their competitors.

Correspondence: Paul D. Harker-Murray, MD, PhD, Pediatric Oncology, Midwest Children's Cancer Center, 8701 Watertown Plank Road, MFRC3018, Milwaukee, WI 53226. Email: pharker@mcw.edu
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