More than 90% of patients with limited-stage Hodgkin lymphoma had PET-negative disease after undergoing treatment with induction ABVD therapy followed by consolidation with the anti-CD30 conjugate brentuximab vedotin, according to the results of a phase II study (Abstract 7508) presented Sunday, June 5, during the Oral Abstract Session on Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia.
In addition, all patients who were PET-negative for disease after treatment with brentuximab vedotin remained in remission with an estimated 1-year progression-free survival of 100%, according to Steven I. Park, MD, of UNC Lineberger Comprehensive Cancer Center, who presented the results.
Dr. Steven I. Park
The current standard of care for limited-stage Hodgkin lymphoma is two to four cycles of ABVD followed by consolidation radiation or three to six cycles of ABVD without radiation. Although radiation appears to improve progression-free survival, it has no significant effect on overall survival, and its use in these patients remains controversial.
“Radiation therapy, although effective, leads to long-term complications including increased risk of secondary malignancies,” Dr. Park told ASCO Daily News. “Patients who receive radiation to the mediastinum are at increased risk for breast cancer, lung cancer, and thyroid malignancies, and there is an increased risk of cardiac complications such as coronary artery disease, valvular heart disease, and heart failure.”
Deciding whether or not to use radiation can be difficult, Dr. Park said, because clinicians want to treat patients with the most effective therapy but are also aware that these patients can live for decades after being treated and want to minimize long-term complications.
This phase II multicenter study enrolled 41 patients with newly diagnosed limited-stage, non-bulky Hodgkin lymphoma and treated them with two cycles of ABVD followed by an interim PET scan. Patients with favorable disease and a negative PET scan after two cycles of ABVD went directly to consolidation therapy with brentuximab vedotin consolidation every 3 weeks for six cycles. All other patients received an additional two to four cycles of ABVD based on risk factors and interim PET scan, and then received brentuximab vedotin consolidation. After brentuximab, patients with a negative restaging PET scan received no additional therapy and those with a positive PET scan received radiation. The median age of patients was 28.
The primary objective of the study was to estimate the proportion of patients who were PET negative after ABVD followed by consolidation therapy.
The majority of patients on trial received four or fewer cycles of ABVD. After two cycles of ABVD, 72.5% of patients achieved PET-negative disease, and after completion of brentuximab vedotin therapy, 94.4% of patients were PET-negative.
With a median follow-up time of 17 months, the estimated 1-year progression-free survival was 91% (95% CI [75%, 97%]), and the estimated 1-year overall survival was 97% (95% CI [81%, 100%]). Patients who achieved a negative interim PET scan after two cycles of ABVD had an estimated 1-year progression-free survival of 96% compared with 79% in patients with a positive interim PET scan. All patients with a negative PET scan at the end of therapy remain in remission with an estimated 1-year progression-free survival of 100%.
After completing consolidation therapy, two patients had confirmed refractory/relapsed disease. One patient had a positive PET scan and declined treatment with radiation to undergo autologous stem cell transplant; that patient remains in remission. Another patient received radiation therapy and also underwent stem cell transplant and remains in remission.
Peripheral neuropathy was the most commonly occurring adverse event. Other common adverse events were rash, fatigue, nausea, and neutropenia. All grade 4 or worse adverse events occurred in one patient who developed a fever and hepatic dysfunction after the first dose of brentuximab vedotin. In addition, this patient developed pancreatitis and eventually died of sepsis. According to Dr. Park, hepatotoxicity and pancreatitis are known, but extremely rare, conditions associated with the drug.
Dr. Park said that, overall, the results of this trial compare favorably with other trials in Hodgkin lymphoma that have attempted to eliminate radiation therapy from the management of this disease.