Adding Opdivo to Chemo May Prolong Survival in Advanced Hodgkin Lymphoma

Patients with advanced-stage classical Hodgkin lymphoma treated with Opdivo (nivolumab) plus the chemotherapy regimen doxorubicin, vinblastine and dacarbazine (AVD) had prolonged survival without disease progression compared with those treated with Adcetris (brentuximab vedotin) plus AVD, recent trial results demonstrated.

Findings from the phase 3SWOG S1826 trial were presented during the 2023 ASCO Annual Meeting.

At a median follow-up of 12.1 months, results showed that patients who received Opdivo plus AVD (489 patients) experienced a one-year estimated progression-free survival (the time during and after treatment when a patient with cancer is alive without disease worsening) rate of 94% compared with 86% among patients treated with Adcetris plus AVD (487 patients). Importantly, Opdivo plus AVD improved progression-free survival compared with Adcetris plus AVD across subgroups.

“The primary (progression-free survival) endpoint crossed the protocol-specified statistical boundary, signifying that the trial had met its primary endpoint,” Dr. Alex F. Herrera, associate professor in the division of lymphoma at City of Hope in Duarte, California, said. “(Opdivo)/AVD reduced the risk of disease progression or death by (approximately) half.”

SWOG S1826 was a trial that enrolled patients with newly diagnosed stage 3 or 4 classical Hodgkin lymphoma. Patients were randomly assigned to receive either Opdivo or Adcetris. Both groups also received AVD.

The primary focus of the study was progression-free survival. Researchers also focused on event-free survival (the time after treatment when a patient with cancer is free of complications or events that treatment aimed to delay or prevent), overall survival (the time when a patient with cancer is still alive), complete response rate (the disappearance of all signs of cancer as a result of treatment) and patient-reported outcomes.

Patient characteristics at the start of the study were well-balanced between the two arms; the median ages were 27 years and 26 years in the Opdivo and Adcetris arms, respectively. Most patients in both arms had stage 4 disease (62% versus 65%).

“SWOG S1826 was a representative trial,” Herrera said. “A quarter of patients were under the age of 18 (years, and) 10% of patients were over the age of 60 (years). A quarter of patients were Hispanic or Black. We had quite good representation from higher-risk clinical subgroups, more so than in (other) modern trials. This was a real-world trial.”

Additional findings revealed that the estimated one-year event-free survival rates were 91% versus 84% in the Opdivo and Adcetris arms, respectively. The one-year overall survival rates were 99% versus 98%, respectively.

The progression-free survival benefit with Opdivo plus AVD over Adcetris plus AVD was consistent across subgroups, including age, International Prognostic Score (which predicts a patient’s freedom from disease progression and overall survival) and disease stage. The benefit was most pronounced among patients over 60 years of age, those with an International Prognostic Score of 4 to 7 (the higher the score, the lower the percentage of freedom from progression and overall survival) and those with stage 4 disease.

The most common any-grade side effects in the Opdivo arm (483 patients) included neutropenia (lower than normal number of neutrophils, a type of white blood cell; 55%), increased alanine transaminase (which may indicate liver damage; 32%) and sensory neuropathy (loss of sensation throughout the body; 29%). These side effects occurred at any-grade at rates of 32%, 41% and 55%, respectively, in the Adcetris arm (473 patients).

In the Opdivo arm, severe or worse side effects included neutropenia (47%), anemia (6%) and thrombocytopenia (low number of platelets in blood; 2%). These side effects occurred at severe or worse levels in the Adcetris arm at rates of 25%, 9% and 3%, respectively.

Infectious toxicity, peripheral neuropathy and immune-related toxicities were all side effects of special interest. Febrile neutropenia (fever and low levels of neutrophils, which may impact how the body fights infections; 5%), sepsis (2%) and infections/infestations (5%) were present sparingly in the Opdivo arm. These toxicities occurred at rates of 7%, 3% and 8%, respectively, in the Adcetris arm.

Peripheral sensory neuropathy (29%) and peripheral motor neuropathy (4%) of any grade were reported in the Opdivo arm; the severe or worse incidence of these events was 1% and 0%, respectively. In the Adcetris arm, rates of any-grade peripheral sensory neuropathy and peripheral motor neuropathy were 55% and 7%, respectively, and the severe or worse rates for these side effects were 8%, and 1%, respectively.

“There was certainly more bone pain in the (Adcetris) arm, (which was) associated with granulocyte colony-stimulating factor use,” Herrera said. “Most importantly though, there was no increase in infectious toxicity, even though there was more neutropenia in the (Opdivo)/AVD arm.”

Eleven percent of patients stopped treatment with Opdivo compared with 22% who ceased treatment with Adcetris. Reasons for discontinuation included side effects (8% versus 12%), progression/relapse (0% versus 1.4%) and death on treatment (0.4% versus 1.6%). Twenty-two and 30 patients, respectively, were still on treatment at the time of the analysis.

“SWOG S1826 was a key step towards harmonizing pediatric and adult therapy of Hodgkin lymphoma,” Herrera said. “Based on these data, (Opdivo)/AVD is poised to be a new standard therapy for advanced stage Hodgkin lymphoma.”

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