Abstract
Classic Hodgkin lymphoma (cHL) is associated with excellent cure rates with front line therapy; however, relapses occur in about 10-20% of patients. Salvage therapy and autologous stem cell transplant is the standard of care treatment approach for relapsed/refractory cHL resulting in cure rates of 50-60%. Relapse rates are higher for patients with certain high-risk features. Addition of post-transplant consolidation brentuximab vedotin (BV) has led to significantly higher 5 year progression free survival rates of 60%. Patients who progressed after autologous stem cell transplant had overall survival of 2-3 years. cHL is remarkably sensitive to PD-1 inhibitors, due to overexpression of PD-L1 on Hodgkin Reed Sternberg cells that interact with PD-1 on immune effector cells in the tumor microenvironment. Studies have also shown that PD-1 inhibitors may increase naïve T cells in peripheral blood and recruit them to cHL tumor microenvironment to facilitate anti-tumor responses. PD-1 inhibitors containing salvage regimens have led to response rates approaching 90-100% in relapsed/refractory cHL. Patients who undergo autologous transplant immediately after PD-1 inhibitor-based therapy have 2 year progression free survival of ~93%, which is significantly higher than patients who undergo autologous transplant after chemotherapy or BV based regimens. Even in patients who undergo autologous transplant in complete response, PD-1 inhibitor-based therapy prior to autologous transplant is associated with post-transplant PFS of 97%, significantly higher than chemotherapy or BV. This finding raises the possibility that PD-1 inhibitors may induce cure in relapsed/refractory cHL, not just by improving depth of response but also by affecting post-transplant immune reconstitution. The remarkable outcomes of PD-1 inhibitors in relapsed/refractory cHL raises a question whether these patients can be cured without autologous transplant. Future large randomized clinical trials are needed to answer this question.