Advanced Hodgkin lymphoma patients experience enhanced survival through immunotherapy, according to research findings.
The treatment method, comprising the immunotherapy medication nivolumab alongside three distinct chemotherapies, demonstrated a two-year relapse-free survival rate of 92% in a phase three trial, as reported in the New England Journal of Medicine on Wednesday.
As expressed by Dr. Jonathan Friedberg, the primary researcher and head of the Wilmot Cancer Institute at the University of Rochester, during a press briefing, "At two years, 92% of the patients did not experience a relapse, the Hodgkin lymphoma did not advance, and no deaths were reported."
Dr. Friedberg further elaborated, "Progression-free survival is typically the primary objective of studies examining Hodgkin lymphoma, as it's thought to accurately predict future outcomes. If we can keep patients disease-free and alive for two years, it's likely that beyond two years, there won't be many significant events. Therefore, we are hopeful that these results will be enduring. However, it's crucial to track these patients for an extended period."
Hodgkin lymphoma is a type of cancer that develops within white blood cells known as lymphocytes, affecting the lymphatic system, a fundamental component of the body's immune system.
According to the American Cancer Society, approximately 8,000 new cases will be identified in the United States this year, and around 900 individuals will pass away from the disease. Hodgkin lymphoma can occur at any age, with early adulthood being the most common period. The average age at diagnosis is 39, and it's the most frequently diagnosed cancer in adolescents aged 15 to 19.
‘An immunotherapy breakthrough’
This new study enrolled around 1,000 individuals who were at least 12 years old and had recently been diagnosed with stage III or IV Hodgkin lymphoma that had not undergone previous treatment.
Between July 2019 and October 2022, the patients were assigned randomly to receive one of two treatment regimens. Four hundred ninety-six patients received the antibody drug brentuximab vedotin along with doxorubicin, vinblastine, and dacarbazine, while 498 others received nivolumab coupled with the same trio of chemotherapies.
The treatments were administered intravenously on the initial day, then approximately two weeks later, within a 28-day cycle. This was repeated for six cycles. The patients were based at 256 locations across the United States and Canada. The trail was sponsored, in part, by Bristol-Myers Squibb, which manufactures nivolumab and supplied the drug for the study.
For years, a blend of chemotherapies has been the standard treatment for advanced-stage Hodgkin lymphoma. However, the researchers closely observed each patient to assess their response to the drug combinations.
The researchers found that the nivolumab treatment regimen led to a significant enhancement in survival compared to the brentuximab vedotin regimen. Two years after initiating treatment, 92% of patients in the nivolumab group remained alive without relapse and without cancer progression, contrasted with 83% of those in the brentuximab vedotin group.
The patients who did not experience cancer progression did not necessitate radiation therapy, which can result in severe side effects such as increased cancer risk or fertility issues. In the study, seven patients required radiation therapy in total.
The researchers remarked that there were more adverse side effects in the brentuximab vedotin group compared to the nivolumab group, but neutropenia – characterized by insufficient levels of a specific type of white blood cell – was more prevalent in the nivolumab group. Neutropenia occurred in 56% of patients administered nivolumab and 34% of patients receiving the brentuximab vedotin treatment.
Dr. Friedberg asserted, "The one side effect that we observed to be more common in the nivolumab arm was neutropenia, which can increase the risk of infection."
The researchers were aware of the potential for neutropenia with brentixuimab, so over 90% of the patients provided the treatment with a "growth factor" medication to mitigate the neutropenia side effect. Conversely, only 50% of patients in the nivolumab group received that "growth factor" support.
"So it's not particularly surprising that we'd see a somewhat higher risk of neutropenia," Dr. Friedberg said.
The researchers concluded that, overall, the nivolumab strategy had a more favorable side-effect profile, with fewer patients discontinuing treatment prematurely, fewer deaths during treatment, and a low incidence of immune-related toxic effects.
There were seven deaths from any cause in the nivolumab group, with three deaths occurring during treatment, contrasted with 14 in the brentuximab vedotin group, with eight deaths occurring during treatment, according to the study.
Dr. Friedberg stated, "In the context of a disease in which a high proportion of patients are cured with standard therapy, and the bar to alter practice is set high, the improvement in efficacy and the risk of adverse events was clinically significant."
Since the study followed patients only for two years, the researchers plan to continue monitoring them and share updates, Dr. Friedberg said. The researchers hope the US Food and Drug Administration will soon decide whether nivolumab should be included as a standard treatment for stage III or IV Hodgkin lymphoma, and they plan to initiate the formal process to request the agency to expand nivolumab's approval in the near future.
Nivolumab, sold under the title Opdivo, has been given the green light by the FDA to be incorporated into treatment plans for various types of cancer, such as small cell lung cancer, melanoma, and urothelial carcinoma. The exact cost of a nivolumab treatment for Hodgkin lymphoma remains uncertain, but a 240-milligram infusion - the highest dosage administered to patients in the recent trial - every fortnight comes with a listed price of $7,635 per infusion, according to Bristol Myers Squibb's pricing details.
"We're in the thick of an immunotherapy revolution in cancer treatment," stated Friedberg.
"For decades, we've been pushing and failing, and in the last six to 10 years, we've seen significant shifts not just in Hodgkin lymphoma but in common cancers like lung cancer and melanoma as well," he continued. "Unfortunately, for many common cancers, although immunotherapy shows promise, it's not a definitive cure. Most of the research now is focused on combining immunotherapy with other conventional methods to see if this combination, in essence, could potentially offer a cure."
"A shift in the standard of care"
Numerous insurance companies have been approving the use of nivolumab in conjunction with chemotherapies as an off-label treatment for Hodgkin lymphoma, mentioned Dr. Ann LaCasce, head of the Dana-Farber/Mass General Brigham Fellowship in Hematology/Oncology.
"The publication of this randomized clinical trial offers high-level evidence supporting the regimen’s use," LaCasce, a lymphoma specialist not involved in the new study, wrote in an email.
"This is a significant study that brings about a shift in the standard of care for pediatric and adult patients in the U.S. with advanced stage classic Hodgkin lymphoma," she said. "The trial was a successful collaborative effort between adult and pediatric investigators and featured a diverse pool of patients in terms of age, race, and ethnicity. This sets the stage for future collaborative studies."
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The conventional method of Hodgkin lymphoma treatment has predominantly focused on the application of chemotherapy drugs and radiation therapy to eliminate cancer cells, expressed Dr. James Armitage of the University of Nebraska Medical Center and Dr. Dan Longo of Brigham and Women’s Hospital in an editorial published alongside the new study.
"However, advances in cancer biology proposed alternative methods of cancer treatment, both in general and specifically for Hodgkin's lymphoma," the two experts said.
"The nivolumab regimen is straightforward to administer, is connected with minimal side effects, and demonstrates impressive efficacy," they wrote, adding that the latest trial suggests that the nivolumab approach "may become the preferred treatment option" for all stages of Hodgkin's lymphoma.
This new study has shown promising results with the use of immunotherapy medication nivolumab, leading to a higher two-year relapse-free survival rate of 92% in patients with advanced-stage Hodgkin lymphoma compared to a 83% rate with brentuximab vedotin. Regular monitoring of patients is essential to confirm the enduring nature of these results and track potential long-term side effects.
In light of these findings, continued use of nivolumab in conjunction with chemotherapies as a treatment option for Hodgkin lymphoma may lead to a significant improvement in patient outcomes and potentially contribute to a shift in the standard of care.
