Infliximab inhibits immune-related adverse events in some cancers, study shows

By Naveed Saleh, MD, MS
Published April 16, 2021

Key Takeaways

Early initiation of highly immunosuppressive infliximab (IFX) and high-dose systemic steroid administration should be considered for diarrhea/colitis and other immune-related adverse events (irAEs) in the setting of immune checkpoint inhibitor treatment, according to the results of a retrospective study published in Molecular and Clinical Oncology.

“Immune‑related adverse events, which often occur in association with immune checkpoint inhibitor (ICI) treatment, require early detection and appropriate management considering their potentially fatal outcomes,” the authors wrote. “Among irAEs, diarrhea/colitis occurs particularly frequently, and serious complications, such as intestinal perforation, may follow unless timely and appropriate treatment is provided.”

In the current study, researchers examined the outcomes of IFX treatment in Japanese cancer patients who developed severe steroid-resistant irAEs secondary to various ICIs. They also assessed the efficacy and safety of IFX in the treatment of such irAEs.

Researchers examined outcomes in eight patients with different types of cancers. Of these patients, four had malignant melanoma, three had lung cancer, and one had renal cancer. These patients developed severe steroid-resistant irAEs after treatment with anti‑PD‑1, anti‑PD‑L1, and anti‑CTLA‑4 antibody preparations. Assessed data included patient background, examination data, imaging data, and treatment progress. They also assessed reactions via the Common Terminology Criteria for Adverse Events version 4.0.

The investigators noted grade 3 diarrhea/colitis in seven of eight patients, and disseminated intravascular coagulation and myocarditis due to autoimmune activation in one patient. The median duration between systemic steroid and IFX treatments was 9 days, with three patients responding to IFX. Of note, one patient responded to IFX after one dose, while two patients responded after two doses. 

The investigators found that the complications improved to grade 0 following a median of 18 days, and no AEs were induced by IFX. Additionally, anti-cytomegalovirus (CMV) and antibacterial agents for CMV and Clostridium difficile (CD) infections were administered to seven patients. The one patient who responded to one dose of IFX did not require this intervention.

“Early initiation of IFX treatment in conjunction with systemic steroid therapy should be considered for severe diarrhea/colitis and other irAEs,” wrote the authors. “However, the possibility for CMV and CD infections should be recognized, and for these the treatment strategy may need to be modified at an early stage.”

The researchers also recommended that re-evaluation for possible infections should be prompt. Importantly, clinicians should consider changing treatment to cyclosporine or vedolizumab if irAEs fail to respond to steroids or IFX treatment.

ICIs can bolster the immune system of cancer patients and thus contribute to disease treatment. These drugs work by blocking endogenous factors—such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1)—thereby promoting antitumor effects. ICIs prolong overall survival in different types of cancer and are approved in many countries.

For various irAEs due to ICIs, guidelines issued by the American Society of Clinical Oncology detail a management algorithm based on organ system involvement. Steroid therapy with prednisolone approximately 1 mg/kg per day is pursued for grade 3 diarrhea/colitis. If symptoms do not improve, IFX at 5 mg/kg per day can be administered.

In the literature, various case reports have described successful treatment of steroid-resistant ICI-induced diarrhea/colitis with IFX. Clinicians often chose single-dose IFX administration for irAE treatment, with the administration of additional doses when no improvements were noted after the first dose. According to previous research, the inhibition of tumor necrosis factor-α (TNF-α) following ICI administration could prevent severe colitis. Infliximab is an anti-TNF-α antibody drug that attaches to and neutralizes TNF-α.

Possible adverse effects of IFX include transient headache and nausea, however these are mild. In addition to symptoms of infectious reactions, clinicians must keep watch for medium- and long-term complications of aplastic anemia, malignant tumor, demyelinating diseases, autoimmune diseases, and heart failure.

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