Stephen M. Ansell

Perinatal and Early-Life Exposures and Risk of Non-Hodgkin Lymphoma

Simple Summary Perinatal and early-life factors have been hypothesized to influence non-Hodgkin lymphoma (NHL) risk, but study results have been mixed and exposure data for childhood ages are limited. In this case–control study of 2280 NHL cases and 2253 controls, we assessed perinatal and early-life factors in association with risk of developing NHL later in life. Greater weight at birth, in childhood, and in late adolescence were all associated with greater risk of NHL. Breastfeeding duration of >6 months compared to never being breastfed was inversely associated with NHL risk. We did not observe any statistically significant associations for other perinatal and early life factors evaluated, and overall associations did not substantively vary by major NHL subtype. Excess body weight across the life course, including in early life, may influence risk of developing NHL later in life.

Safety, feasibility, and efficacy of anti-PD-1 therapy for the treatment of classical Hodgkin lymphoma.

The clinical paradigm for treatment of classical Hodgkin lymphoma has been transformed by the use of anti-PD-1 therapy, driven by foundational work revealing near-universal 9p24.1 alterations resulting in overexpression of PD-L1 and PD-L2 on Reed-Sternberg cells. Use of PD-1 inhibitors has demonstrated remarkable clinical activity for patients with Hodgkin lymphoma. Anti-PD-1 monotherapy has demonstrated durable remissions in the relapsed/refractory setting, including a 5-year overall survival of around 70% in clinical trials. Further efforts have evaluated these treatments in various combinations and demonstrated efficacy in both the salvage setting prior to stem cell transplantation (SCT) and the relapsed/refractory setting after SCT. After such promising results, these agents were moved into the frontline setting with landmark trials such as SWOG S1826, establishing Nivo-AVD (nivolumab, doxorubicin, vinblastine, dacarbazine) as an emerging standard for advanced-stage classical Hodgkin lymphoma. Similarly, Nivo-AVD in the NIVAHL trial demonstrated remarkable efficacy in early stage, unfavorable disease. These agents have a unique mechanism of action that shows promise for patients who would otherwise be chemotherapy-ineligible. The use of these agents is also of interest in the adolescent and young adult populations who would be at risk from long-term side effects of chemotherapy or radiation. This review seeks to examine the safety, efficacy, and feasibility of anti-PD-1 therapy in classical Hodgkin lymphoma.

Safety, feasibility