A Phase 3 trial has demonstrated that patients with advanced stage (3 or 4) classic Hodgkin lymphoma who underwent initial treatment with nivolumab, a PD-1 checkpoint inhibitor, and AVD chemotherapy (N-AVD) had a significantly lower risk of their cancer getting worse than patients treated with brentuximab vedotin, a monoclonal antibody, and AVD (BV-AVD) a yr after starting treatment.

Ninety-four percent of adolescent and adult patients within the N-AVD group had progression-free survival compared with 86% within the BV-AVD arm. N-AVD was also well-tolerated as there have been few serious immune-related uncomfortable side effects within the S1826 trial. The median follow-up was 12.1 months.

These late-breaking findings will likely be presented by City of Hope’s Alex Herrera, M.D., at ASCO’s 2023 Plenary Session, June 4, at 2:53 p.m. CT in Hall B1 and will likely be featured within the official ASCO press program.

Lead investigator on the study, Herrera is chief of the Division of Lymphoma at City of Hope, one in all the biggest cancer research and treatment organizations in america, and is an investigator with the SWOG Cancer Research Network, a clinical trials group funded by the National Cancer Institute (NCI), a part of the National Institutes of Health.

The outcomes are remarkable. The mixture of nivolumab and chemotherapy is potent and secure in patients with Stage 3 or 4 classic Hodgkin lymphoma as an initial treatment. The therapy is poised to be a normal for treatment of advanced Hodgkin lymphoma. That is indeed great news for patients with this cancer as there may be one other effective and secure treatment option for them.”

Alex Herrera, M.D., Chief of the Division of Lymphoma, City of Hope

Georgie Garabet, 43, of Glendora, California, was one in all the patients who participated within the trial. When Garabet began to feel sick in early 2020, he was a 40-year-old father of two children under the age of three. His symptoms included uncontrollable itching throughout his body and severe weight reduction. After a number of trips to emergency rooms and to his primary care doctor, he was eventually diagnosed with Stage 3 Hodgkin lymphoma.

“I panicked once I heard the word cancer,” Garabet said. At the identical time, he was relieved to know what should be blamed for his symptoms.

Garabet met Herrera and immediately felt he was in good hands. “He explained every part so well,” he added. Garabet enrolled within the trial. After his first infusion, he felt exhausted but that was the worst he felt during treatment. After only 4 infusions, he was in remission. He was advised to proceed the treatment in case any cancer lingered, and he did. “Now when people tell me they’ve cancer, I tell them to not panic. There are lots of cures now,” he added.

The S1826 trial, supported by the NCI and led by SWOG, is the biggest classic Hodgkin lymphoma study ever conducted within the NCI’s National Clinical Trials Network and can be representative of a various patient population. A few quarter of the enrolled patients were Black or Hispanic. A partnership with the Kid’s Oncology Group (COG) helped make sure the trial included young adolescents, and 1 / 4 of enrolled patients were younger than 18 years old. Nearly two-thirds of all patients had Stage 4 cancer.

“This study speaks to the ability of the National Clinical Trials Network and is a superb example of the transformative work that the NCI funds,” said Jonathan Friedberg, M.S., M.M.Sc., senior writer of the study, chair of the SWOG Cancer Research Network’s lymphoma committee and director of the Wilmot Cancer Institute on the University of Rochester. “Hodgkin lymphoma shouldn’t be a typical disease and the NCTN enabled a big network of greater than 200 pediatric and adult community providers and academic medical centers to work together. Due to that, we were capable of get data in a short time and directly impact patient care. This was a critical investment in cancer research and treatment.”

Patients with Stage 3 or 4 classic Hodgkin lymphoma who had not been previously treated and were age 12 or older were eligible for the trial. Of a complete of 976 eligible patients, 489 were enrolled within the N-AVD arm (nivolumab plus Adriamycin, vinblastine and dacarbazine), while 487 were a part of the BV-AVD group. Each group received six infusion cycles of every combination therapy.

As expected with combination chemotherapy, essentially the most common uncomfortable side effects included gastrointestinal and hematologic toxicities, and fatigue. Nonetheless, lower than 1% of patients needed radiation after trial treatment, which is a dramatic reduction within the proportion of patients being initially treated for Hodgkin lymphoma who need radiation, especially amongst pediatric patients.

“The flexibility to take care of high rates of relapse-free survival with minimal use of radiation therapy in children with newly diagnosed advanced stage Hodgkin lymphoma will likely be a paradigm shift,” said Sharon Castellino, M.D., M.Sc., chair of the COG Hodgkin lymphoma committee and director of the Leukemia and Lymphoma Program on the Aflac Cancer and Blood Disorders Center, Kid’s Healthcare of Atlanta, Winship Cancer Institute at Emory University.

Brentuximab vedotin was the primary antibody–drug conjugate developed for traditional Hodgkin lymphoma. Several studies have demonstrated that incorporating the therapy into frontline treatment improves progression-free survival and overall survival. Despite improved outcomes, there are still serious uncomfortable side effects; relapses can occur.

“There is certainly a necessity to enhance frontline therapies for Hodgkin lymphoma, particularly because a disproportionate variety of patients with this disease are teens and young adults,” Herrera added.

PD-1 checkpoint inhibitors are a strong and growing type of immunotherapy used to treat melanoma, kidney cancer, head and neck cancers, relapsed or difficult to treat Hodgkin lymphoma and other cancers. The PD-L1 protein is expressed on Hodgkin lymphoma tumor cells and aids the cancer by signaling to immune cells, comparable to T cells, to stop working against tumors.

Checkpoint inhibitors block the PD-L1 protein to assist the immune system and, specifically, T cells, do what they’re designed to do, eradicate cancer. On this study, adding nivolumab to chemotherapy worked so well that some patients experienced remission after only a number of treatments.

Next steps for the trial include following patients to measure the sturdiness of progression-free survival, overall survival and other patient outcomes.

Funding was provided by: National Cancer Institute of the National Institutes of Health U10CA180888, U10CA180819, U10CA180820, U10CA180821, U10CA180863, U10CA180886 and Bristol-Myers Squibb through a Cooperative Research and Development Agreement between the NCI and BMS. Brentuximab vedotin was provided by Seagen.

Along with Herrera and Friedberg, co-authors on the presentation include Michael L. LeBlanc, Ph.D., SWOG Statistical Center and Fred Hutchinson Cancer Center; Sharon M. Castellino, M.D., M.Sc., Emory University, Aflac Cancer and Blood Disorders Center, Kid’s Healthcare of Atlanta; Hongli Li, M.S., SWOG Statistical Center and Fred Hutchinson Cancer Center; Sarah C. Rutherford, M.D., Weill Cornell Medicine-Latest York Presbyterian Hospital; Andrew M Evens, D.O., M.Sc., Rutgers Cancer Institute of Latest Jersey; Kelly Davison, M.D., McGill University; Angela Punnett, M.D., Hospital for Sick Children, Toronto; David C. Hodgson, M.D., M.P.H., Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network; Susan K Parsons, M.D., M.R.P., Tufts Medical Center, Tufts University School of Medicine; Sairah Ahmed, M.D., University of Texas MD Anderson Cancer Center; Carla Casulo, M.D., Division of Hematology/Oncology, University of Rochester; Nancy L. Bartlett, M.D., Washington University School of Medicine in St. Louis; Joo Y. Song, M.D., Department of Pathology, City of Hope; Richard F. Little, M.D., Cancer Therapy Evaluation Program, National Cancer Institute; Brad S. Kahl, M.D., Washington University School of Medicine in St. Louis; John P. Leonard, M.D., Weill Cornell Medicine-Latest York Presbyterian Hospital; Sonali M. Smith, M.D., Department of Oncology, University of Chicago; and Kara M. Kelly, M.D., Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center.

Source:

SWOG Cancer Research Network