Treating R/R Classic Hodgkin Lymphoma: Ipilimumab and Other Approaches

Relapsed or refractory classic Hodgkin lymphoma (R/R cHL) occurs in an estimated 25 percent of cHL patients. While both conditions are challenging to treat, ipilimumab has shown promise as an immunotherapy because it aids in blocking the CTLA-4 protein, which exhibits overactivity on T cells in cHL. However, there are still questions surrounding the treatment’s efficacy for long-term care.

Ipilimumab in Patients with R/R cHL

At the 2024 American Society of Hematology Annual Meeting and Exposition, researchers revealed their findings on ipilimumab’s efficacy alone or in combination with nivolumab, another immune checkpoint inhibitor, in patients with R/R cHL who had progressed after PD-1 inhibitors. The study was divided into two groups: one for patients with stable or partial responses to PD-1 therapy and another for patients who exhibited disease progression on PD-1 treatment.

Among 13 patients who had progressed after PD-1 inhibitors, 23 percent had a partial response to ipilimumab alone, but none achieved a complete response. When ipilimumab was combined with nivolumab, none of the patients responded to the treatment.

Most patients discontinued treatment due to disease progression, toxicity, or personal choice. Side effects included fever, ALT elevation, cough, and gastrointestinal issues. Some patients experienced more serious adverse events, such as:

• ALT/AST elevation
• Abdominal pain
• Cytokine release syndrome
• Dyspnea
• Lung infection
• Thrombocytopenia
• Urinary tract infection
• Colitis
• Diarrhea
• Hyponatremia
• Anorexia

Despite its abilities to block the CTLA-4 protein, ipilimumab showed insufficient success and notable toxicity as a standalone cHL treatment among high-risk patients with multiple previous relapses.

Alternatives to Ipilimumab as a cHL Treatment

There are several alternative treatments to consider for R/R cHL patients who are not responding to ipilimumab:

• Brentuximab vedotin is an antibody-drug conjugate that targets CD30, a protein found on the surface of Hodgkin lymphoma cells. It has shown significant effectiveness in R/R cHL, especially when combined with other therapies or following stem cell transplant.
• ICE (ifosfamide, carboplatin, etoposide), a combination chemotherapy regimen, is often used in patients with relapsed cHL who are not candidates for further treatment with brentuximab vedotin or checkpoint inhibitors.
• Radiation therapy can sometimes be used for localized areas of relapse or in cases where the cancer is limited to a single region. It is less commonly used as a first-line treatment in relapsed cHL but may be effective in certain cases.

Each of these alternatives differs in efficacy and safety. When choosing the right treatment, a personalized approach that accounts for factors like response to prior therapies is key.

References:

Merryman, R. (n.d.). Ipilimumab with and without nivolumab in patients with classic Hodgkin lymphoma with progression after PD-1 blockade. ash.confex.com. https://ash.confex.com/ash/2024/webprogram/Paper203414.html

Montanari, F., & Diefenbach, C. (2014, September). Relapsed Hodgkin lymphoma: Management strategies. Current hematologic malignancy reports. https://pmc.ncbi.nlm.nih.gov/articles/PMC4909353/#:~:text=Despite%20the%20favorable%20outcome%20for,with%20standard%20salvage%20therapies2.