Frontline CD30 ADC for Advanced Classical Hodgkin Lymphoma - Episode 1

Frontline Treatment of Classical Hodgkin Lymphoma

June 26, 2019

Siddhartha Ganguly, MD, FACP:Welcome to thisTargeted Oncologypresentation in Precision Medicine called, “Frontline CD30 ADC for Advanced Classic Hodgkin Lymphoma.” I’m Dr Sid Ganguly. I’m the director of the Lymphoma and Myeloma Program at the University of Kansas Medical Center, Kansas City, Kansas. Joining me today is my colleague Dr Ahmed Galal, a cell therapy and hematologic malignancies specialist at Duke Cancer Center in Durham, North Carolina.

Targeted therapies have really come to the forefront for the treatment of cancer. Today we are going to talk about an important therapeutic approach that has shown great promise in treating advanced Hodgkin lymphoma, called brentuximab vedotin. It has recently received approval, in combination with chemotherapy, as frontline treatment of advanced classic HL [Hodgkin lymphoma]. This agent represents a paradigm-changing advance in precision oncology and drug development for patients with classic Hodgkin lymphoma. Dr Galal, let’s get started.

We get this question asked, “What does Hodgkin lymphoma consist of, and what’s the difference between classic and lymphocyte-predominant Hodgkin lymphoma?” Both of them arise from postgerminal center B-cells, but there are inherent differences between classic and the LPHL, which is a lymphocyte-predominant Hodgkin lymphoma. The cells that diagnose a patient with Hodgkin lymphoma, called Hodgkin and Reed-Sternberg cells, or HRS cells. And they are identified by a large multinucleated cell—sometimes with very prominent nucleoli, and sometimes it looks like a set of owl eyes looking at you, and they are stained positively with CD30 and CD15. Whereas, in the LPHD, the cells are CD20-positive and often CD30- and CD15-negative. And those cells, they do...even morphologically from classic Hodgkin lymphoma. And pathologists have often called them cells that look like popcorn. They call them popcorn cells. Not only are they morphologically different, but they also differ in treatment characteristics and long-term outcomes.

Lymphocyte-predominant Hodgkin lymphomas actually have a little better prognosis than classic Hodgkin lymphoma. And their treatment defers from classic Hodgkin lymphoma as well. Dr Galal, could you tell us what role chemotherapy has in treating classic Hodgkin lymphoma?

Ahmed Galal, MD, FRACP, MSc:The role of chemotherapy in classical Hodgkin lymphoma has been established so many years before, almost 40 years, with ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine] being the backbone for chemotherapy in frontline therapy. In the low grade, grade 1 or stage I or II Hodgkin lymphoma, it’s probably the only chemotherapy that we would use up front. Now, in stage III and IV, it’s more of a change because of the brentuximab vedotin addition replacement for the bleomycin with ABVD doxorubicin, bleomycin, vinblastine, dacarbazine. We’re still using the same chemotherapy without the bleomycin with the addition of the brentuximab that actually added advantage for the higher grade, or higher-stage patients.

The unmet needs for Hodgkin lymphoma are in the higher stage and the bulky disease more. These patients tend to relapse at a higher rate than the patients with favorable early disease. When we look at the stage III or IV, the relapse rate after 5 years is about 23%, 25%. These patients, when they relapse, they get further chemotherapy and they probably go for transplant if they are a fit there. But patients who are not a fit for transplant still need further treatment, so there are areas of unmet needs there that probably are filled partially by the brentuximab vedotin.

Transcript edited for clarity.