Clinical Trial Forges New Standard of Care for Advanced Hodgkin Lymphoma

Dr. Douglas Moskowitz
Article Summary
  • Current treatments for Hodgkin lymphoma are highly effective, but there is still room for improvement.
  • An international clinical trial assessed whether the drug nivolumab plus chemotherapy could yield better results in patients with advanced disease.
  • The findings show improved outcomes and are changing clinical practice. Sylvester physician Craig H. Moskowitz, M.D., helped design the study and led the Sylvester trial site.

Adding the immunotherapy drug nivolumab to a mix of chemotherapy drugs outperformed the current standard therapy for advanced Hodgkin lymphoma in a large clinical trial.

The new study is rapidly changing how patients are being treated internationally and at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, said Craig Moskowitz, M.D., Sylvester’s physician-in-chief.

Dr. Moskowitz, who is also a Miller School professor in the Division of Hematology, was Sylvester’s site lead for the multi-site trial and was on the National Cancer Institute steering committee that designed it.

The study was published Oct. 17 in the New England Journal of Medicine.

Trying Something New

Hodgkin lymphoma develops in the lymphatic system and affects about 8,570 people in the U.S. each year. The disease typically hits two population groups – the young and old. It’s the most common cancer in adolescents from age 15 to 19, striking people as they are just setting out on adulthood.

Former Sylvester patient Giovan Seecharan was only 22 when he noticed a mass above his collarbone. He drove to Miami for a biopsy at Sylvester the same day as his graduation ceremony from Florida State University in Tallahassee, Fla.

Dr. Douglas Moskowitz
Giovan Seecharan drove to Miami for a biopsy at Sylvester the same day as his college graduation ceremony.

He was diagnosed with stage 3 Hodgkin lymphoma and signed up for the new clinical trial.

“I thought that, if this is something that can modernize treatments, especially cancer treatments, you can sign me up. I really didn’t hesitate,” said Seecharan, who was one of 20 Sylvester patients enrolled in the 970-patient international trial, funded mainly by the U.S. National Cancer Institute.

The trial compared nivolumab with another drug, brentuximab vedotin, in combination with chemotherapy.

Going Head-to-Head

Brentuximab is a so-called antibody-drug conjugate. It has two key parts: an antibody that homes to a target on the tumor cells and a toxin that eliminates the cells.

Brentuximab is typically combined with three chemotherapy drugs — doxorubicin, vinblastine and dacarbazine, a combination called “AVD.” Brentuximab plus AVD was previously shown to improve survival rates for advanced Hodgkin lymphoma over chemotherapy drugs alone and was approved as a first-line treatment for the condition five years ago.

“This is a better program with less toxicity for patients with stage 3 and 4 disease,” said Dr. Craig Moskowitz.

Nivolumab is a “checkpoint inhibitor” that releases the brakes on the immune system, enabling an immune attack on cancer cells. It’s been shown to be effective in several types of cancer, including melanoma and non-small cell lung cancer.

Nivolumab has also shown promise against Hodgkin disease in earlier-stage studies. A recent phase II trial of Nivolumab plus AVD, for instance, showed low toxicity and high activity against advanced Hodgkin disease, and led to the new clinical trial, said Dr. Moskowitz.

In the new trial, patients with stage 3 or stage 4 Hodgkin lymphoma were randomized to receive either brentuximab plus AVD or nivolumab plus AVD. Patients had “classic” Hodgkin lymphoma, which accounts for the vast majority of cases.

Even Better Outcomes

The new publication reveals that nivolumab plus AVD was superior by several measurements.

One key data point was progression-free survival, a measurement of survival without recurrent disease. Progression-free survival at two years was 83% with brentuximab plus AVD and 92% with Nivolumab plus AVD. The difference in older patients was particularly stark: 65% showed progression-free survival with brentuximab plus AVD compared to 88% with nivolumab plus AVD.

When I heard about Dr. Moskowitz’s expertise, and about how he’s always trying to revolutionize his field, I put all my bets on him.
—Clinical trial participant Giovan Seecharan

In addition, patients on the nivolumab arm of the trial had fewer side effects, with only 9.4% discontinuing the drug, compared with 22.2% discontinuing brentuximab.

“At the end of the day, this is a better program with less toxicity for patients with stage 3 and 4 disease,” said Dr. Moskowitz.

The study provides the highest grade of evidence for the National Comprehensive Cancer Network, which develops clinical practice guidelines.

“This will be the new standard of care for advanced-stage Hodgkin lymphoma,” said Dr. Moskowitz.

The corresponding author of the study was Wilmot Cancer Institute Director Jonathan W. Friedberg, M.D., at the University of Rochester Medical Center.

Leading-edge Care

Seecharan was on the arm of the trial that received nivolumab plus AVD. He started a five-month course of treatment in July 2022 and, by February of the next year, was pronounced free of cancer.

He is almost at the two-year mark for remission, a major milestone since very few Hodgkin’s lymphoma patients suffer a recurrence after two years.

“I may never have to go through this ever again,” said Seecharan. “It’s something I can put in the past, for sure. It’s an incredible feeling.”

He said he had full confidence in his care team and his oncologist, Dr. Moskowitz.

“When I heard about Dr. Moskowitz’s expertise, and about how he’s always trying to revolutionize his field, I put all my bets on him,” said Seecharan.

Looking to the Future

Dr. Moskowitz and his team are involved in several other clinical trials for Hodgkin lymphoma. A major goal is to assess if patients can be treated with fewer cycles of therapy, thereby minimizing side effects. For instance, Dr. Moskowitz is the lead U.S. investigator for an international trial assessing this question in early-stage patients treated with brentuximab in combination with chemotherapy.

“We have a number of studies here which give modern therapeutic approaches, where we’re actually trying to cure the patient with less treatment,” said Dr. Moskowitz.

Contributing to clinical research was a positive aspect of Seecharan’s experience at Sylvester, and he’s excited to see the data emerge.

“I’ve always thought about what comes after this journey I’ve had with cancer, and if it’s helping others and also being a part of testing a revolutionary drug, then I’m all for it,” he said.


Tags: cancer research, chemotherapy, Dr. Craig Moskowitz, Hodgkin lymphoma, New England Journal of Medicine, Sylvester Comprehensive Cancer Center, USNWR Oncology