Opdivo Could Boost Outcomes for People Battling Hodgkin Lymphoma
The widely used immunotherapy drug nivolumab (Opdivo) is safer and more effective in treating adults and children with advanced Hodgkin lymphoma than the targeted therapy now used as standard care is, new clinical trial results show.
Nivolumab outperformed the drug brentuximab vedotin (Adcetris), extending progression-free survival by 94% at one year compared to 86%, said lead researcher Dr. Alex Herrera, a hematologist-oncologist at City of Hope in Duarte, Calif.
Nivolumab also produced significantly fewer side effects than brentuximab vedotin, which was the first novel therapy developed for Hodgkin lymphoma, Herrera said in a presentation Sunday at the American Society for Clinical Oncology (ASCO) annual meeting in Chicago.
“Based on these data, nivolumab is poised to be a new standard therapy for advanced-stage Hodgkin lymphoma,” Herrera said.
Hodgkin lymphoma is a type of cancer that starts in white blood cells called lymphocytes, according to the American Cancer Society.
An estimated 8,830 new cases of Hodgkin lymphoma are expected to be diagnosed in the United States in 2023, and 900 patients will die from the cancer, according to ASCO. The five-year survival rate for advanced disease is 83%.
“It disproportionately affects young patients, folks in their teens, 20s, 30s,” Herrera said. “There's a long history of treating this cancer, and over the years we used increasing doses of radiation and increasing doses of chemotherapy to try to maximize care.”
Approved in 2018 as a first-line treatment for adults with advanced Hodgkin lymphoma, brentuximab vedotin is an antibody-based drug that attaches to cancer cells and delivers a drug that causes cell death.
Adding brentuximab vedotin to chemotherapy improved outcomes and survival, but the drug also increased side effects in both adult and pediatric patients, Herrera said.
Further, as many as 60% of pediatric Hodgkin lymphoma patients also needed radiation therapy with this regimen, increasing their risk of long-term health problems.
The advent of nivolumab offered a potential alternative to brentuximab vedotin, Herrera explained.
Some cancer cells carry a protein called PD-L1 that essentially masks them from detection by T-cells. Nivolumab prevents PD-L1 from working, allowing immune cells to target and destroy tumors.
“Hodgkin lymphoma is the poster child for the use of PD-1 blockade,” Herrera said. “There are genetic changes in the Hodgkin lymphoma tumor cell that lead to expression of the PD-1 ligands on the surface of Hodgkin lymphoma cells.”
Nivolumab is already approved to treat a wide array of cancers, including non-small cell lung cancer, melanoma, kidney cancer, head and neck cancer, liver cancer, bladder or urinary tract cancer, colon cancer and esophageal cancer, according to the drug's maker, Bristol Myers Squibb.
For this trial, which was funded by the National Institutes of Health, researchers recruited almost 1,000 patients with Hodgkin lymphoma, 12 or older, who'd not received any treatment.
Half were assigned to receive nivolumab with chemotherapy, and the others got brentuximab vedotin and chemo.
One year out, nivolumab had a 52% reduction in risk of disease-related death compared to brentuximab vedotin, results showed.
Nivolumab patients also had fewer side effects, including less infection, sepsis and neuropathy, Herrera said.
“There was more peripheral neuropathy in the brentuximab vedotin arm, and I can't emphasize enough how important neuropathy is as a side effect in these young patients who have the rest of their life ahead of them,” Herrera said. “It's fantastic to be curing your cancer, but tough to live with not being able to feel your fingers and toes.”
About 22% of patients who got brentuximab vedotin had to discontinue treatment due to side effects, compared with 11% of nivolumab patients, Herrera said.
These results could mean a new standard of care for both adults and children, ASCO Chief Medical Officer Dr. Julie Gralow said.
“I can tell you that the Hodgkin lymphoma docs are really excited about nivolumab,” Gralow said.
Dr. Oreofe Odejide, a hematologic oncologist with Dana-Farber Cancer Institute in Boston, agreed.
“This trial was an unprecedented effort across all North American clinical trial cooperative groups to improve the cure rate in advanced stage Hodgkin lymphoma and harmonize treatment approaches between pediatric and adult patients,” Odejide said in a news release. “The collaborations across adult and pediatric groups helped pave the way for a new standard of care that is better tolerated and results in a higher proportion of patients with durable remissions.”
Findings presented at medical meetings should be considered preliminary until published in a peer-reviewed journal.
The American Cancer Society has more about Hodgkin lymphoma.
SOURCES: Alex Francisco Herrera, MD, hematologist-oncologist, City of Hope, Duarte, Calif.; Julie Gralow, MD, chief medical officer, American Society of Clinical Oncology