Leo I. Gordon, MD, Abby and John Friend Professor of Oncology Research, Northwestern University Feinberg School of Medicine, discusses the promise of checkpoint inhibitors in the treatment of patients with Hodgkin lymphoma.

Checkpoint inhibitors seem to be effective in Hodgkin lymphoma, and researchers over the years have tried to define the best place for this class of drugs in the treatment paradigm, Gordon says. For example, there is an ongoing study looking at single-agent pembrolizumab (Keytruda) followed by the standard regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine in the frontline setting for patients with advanced disease. Early data have been impressive, Gordon says, showing clear decreases in tumor volume even in patients with bulky disease.

The phase II portion of this study, involving approximately 30 patients, has almost reached completion, and researchers are planning a larger phase III study which will focus on patients with large-volume disease. Barring any unforeseen toxicity, Gordan adds, checkpoint inhibition should be here to stay in Hodgkin lymphoma.

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Leo I. Gordon, MD, Abby and John Friend Professor of Oncology Research, Northwestern University Feinberg School of Medicine, discusses the use of checkpoint inhibitors in the treatment of patients with Hodgkin lymphoma.

Dr. Gordon Discusses Use of Checkpoint Inhibitors in Hodgkin Lymphoma

Leo I. Gordon, MD, a professor of medicine at Feinberg School of Medicine, Northwestern University, discusses clinical trials in Hodgkin lymphoma.

Data suggests that the immune system and the use of checkpoint inhibitors may play an important role in Hodgkin lymphoma, says Gordon. These novel agents take the brakes off the immune system so it can attack the disease.

According to Gordon, there are trials comparing ABVD [adriamycin, bleomycin, vinblastine, dacarbazine] with other regimens, but ABVD remains the standard. However, the drug bleomycin causes pulmonary toxicity, especially in patients who are a little bit older with a smoking history.

Dr. Gordon on Clinical Trials in Hodgkin Lymphoma

Leo I. Gordon, MD, professor of medicine, Feinberg School of Medicine, Northwestern University, discusses the role of checkpoint inhibitors for patients with hematologic malignancies.

According to Gordon, there was an international trial of 72 patients who received pidilizumab (CT-011), which is one of the first checkpoint inhibitors. It may not work as a checkpoint inhibitor, but there was very little toxicity associated with the drug.

The PLATFORM study is going to be combining the checkpoint inhibitor durvalumab (Imfinzi) with CAR T cells in patients with diffuse large B-cell lymphoma (DLBCL). It makes sense to combine the checkpoint inhibitors with CAR T cells; however, the safety issues, the dosing, and the sequencing still need to be determined, states Gordon.

Dr. Gordon on the Role of Checkpoint Inhibitors in Hematologic Malignancies

Leo I. Gordon, MD, professor of medicine, Feinberg School of Medicine, Northwestern University, discusses the concerns of chimeric antigen receptor (CAR) T-cell therapy.

When considering the use of CAR T-cell therapy for hematologic malignancies, Gordon first asks, "Does it work?" Preliminary data suggest that it does work in a very heavily pretreated group of patients, with about 50% of patients in remission and 40% to 50% of responses lasting 6 months or longer.

If CAR T-cell therapy works, then Gordon asks, "Is the toxicity manageable?" In an early study of children, researchers found there were issues with neurologic toxicity and blood pressure as well as 4 fatalities from cerebral edema caused by CAR T-cell therapy.

According to Gordon, cell manipulation and how much pre-infusion lymphodepleting chemotherapy are given to balance the growth of the CAR T cells still need to be better understood.

Lastly, what does it cost? There are concerns over the potential financial burden with this type of treatment, he explains. 

Leo I. Gordon, MD

Articles

Dr. Gordon Discusses Use of Checkpoint Inhibitors in Hodgkin Lymphoma

Dr. Gordon on Clinical Trials in Hodgkin Lymphoma

Dr. Gordon on the Role of Checkpoint Inhibitors in Hematologic Malignancies

Dr. Gordon on the Concerns of CAR T-Cell Therapy