ASH 2023: A Shift in Standard of Care for Older Patients with Advanced Stage Hodgkin Lymphoma

Dr. Rutherford presented at the 2023 ASH Annual Meeting about the results of SWOG 1826, a randomized trial for Hodgkin lymphoma patients. Dr. Rutherford shared the study findings with HealthTree. Watch the video here or read the following summary.

Dr. Sarah Rutherford, from Weill Cornell Medicine in New York, presented at the American Society of Hematology Annual Meeting 2023 the results of SWOG 1826, a randomized trial (treatment is selected at random) comparing the monoclonal antibody nivolumab(N) and brentuximab vedotin (Bv) when given with combination therapy doxorubicin, vinblastine, and dacarbazine (AVD) to patients with advanced stage classic Hodgkin lymphoma who have not received any prior therapy.

In the older adult cohort, treatment with N-AVD had a better tolerability profile which by the researchers was considered an outstanding result.

Treatment in Older Patients

Patients older than 60 years represent 15%-25% of patients with classical Hodgkin lymphoma. This older group of patients are often offered smaller doses or fewer cycles of chemotherapy due to decreased chemotherapy tolerance. This fact, along with older patients having simultaneous diseases and lower general well-being, results in lower survival rates than younger patients. Particularly, the primary treatment Bv-AVD can be challenging to administer in older adults due to toxicities like infection and neuropathy (weakness, numbness, and pain in the hands and feet) as shown in the table presented at the event:

The Study

S1836 is phase III trial that aims to compare the progression-free survival (time in which the disease is not growing) of N-AVD vs Bv-AVD in patients newly diagnosed with stage III or IV classical Hodgkin lymphoma aged 12 and older. Overall survival, event-free survival, response rates, and adverse events were assessed as secondary outcomes.

Dr. Rutherford and her team specifically focused on the older patient population, analyzing data from approximately 100 patients within this demographic. The median age of this group was 66 years with 62% being male and 86% being white. No patients received radiotherapy per the study design protocol.

The Results: Nivolumab is Better Tolerated

Safety analysis was performed in 65 patients. Even though blood toxicity was greater in patients on N-AVD (52% vs 38% for Bv-AVD); febrile neutropenia (fever and low blood counts), infection, and sepsis were lower for patients on N-AVD vs Bv-AVD as shown in the tables:

3 times more patients experienced sepsis on Bv-AVD compared to N-AVD.

More than twice as many patients receiving Bv-AVD had peripheral sensory neuropathy compared to N-AVD.

Moreover, the study showed that N-AVD markedly improves progression-free survival (time in which the disease is not growing) over Bv-AVD in this same cohort of older patients, with a 1-year progression-free survival of:

• 93% for N-AVD vs
• 64% for Bv-AVD

Fewer deaths occurred on N-AVD vs Bv-AVD as well, with 1-year overall survival of:

• 95% on N-AVD vs
• 83% on Bv-AVD

The majority of deaths on Bv-AVD occurred due to infection or sepsis:

• 4% for N-AVD vs
• 14% for Bv-AVD

Treatment was discontinued early in:

• 5 patients (10%) on N-AVD and
• 16 patients (33%) on Bv-AVD

Reasons for discontinuation included side effects, but also death and disease progression.

N-AVD Expected to Become Standard of Care

Wrapping up this presented abstract, N-AVD is better tolerated than Bv-AVD in older patients with advanced-stage hodgkin lymphoma.

As a final statement, Dr. Rutherford mentioned that N-AVD is expected to become a standard of care for older patients who are candidates to receive anthracycline-based combination therapy. She has already begun using nivolumab plus AVD in her clinical practice for older patients, indicating a potential shift in the standard of care. This novel treatment regimen not only enhances tolerability but also showcases superior efficacy, providing hope for a more favorable prognosis for individuals facing classical hodgkin lymphoma in their later years.

Follow-up is ongoing to confirm these findings and assess long-term safety.