Chronic Diarrhoea and Colitis in Patients Receiving Immunotherapy Found Associated with Longer Survival

Journal of the National Comprehensive Cancer Network reported a retrospective analysis finding that the use of proton pump inhibitors (PPI), which reduce stomach acid, in cancer patients receiving immune checkpoint inhibitor immunotherapies is a risk factor for chronic immune-mediated diarrhoea and colitis. Another notable finding in the same analysis was that patients experiencing chronic immune-mediated diarrhoea and colitis (BADK) had lower cancer progression.

Immune-mediated diarrhoea and colitis are common side effects of immunotherapy

The severity of this immune-related adverse effect can range from mild, self-limiting diarrhoea to a condition characterized by life-threatening complications, including bowel perforation. Immune-mediated diarrhoea and colitis (BADK) may also have a limited course (acute BADK) or be prolonged (chronic BADK).

• Related topic: What Are the Side Effects of Immunotherapy Drugs, and How Are They Treated? 

The relationship between chronic immune-mediated diarrhoea and colitis and survival 

Although previous studies have identified an association between BADK and prolonged survival in cancer patients treated with immunotherapy, less is known about chronic BADK and its effects on survival or risk factors.

This study included consecutive adult patients with cancer who developed grade 2 or higher diarrhoea / colitis while receiving immunotherapy at the University of Texas MD Anderson Cancer Center between January 2018 and October 2019. Another inclusion criterion was immunosuppressive treatment to manage these side effects: steroids, iximab or vedolizumab as part of BADK management. Exclusion criteria included inflammatory bowel disease and other concurrent gastrointestinal disorders.

Patients were classified according to whether they experienced acute or chronic BADK. A duration of more than 3 months distinguished chronic from acute BADK. Patients with chronic BADK were further characterized as having persistently symptomatic, recurrent (symptoms recurring after a symptom-free period of 1 month or longer), or persistent histological BADK.

Of the 88 patients included, 43 had chronic BADK and 45 had acute BADK. At baseline, the median age was 66 for patients with chronic BADK and 65 for those with acute BADK. Urinary tract (bladder) cancer and melanoma were the most frequently observed diagnoses in both groups.

Results

Risk factors for chronic BADK included;

• PPI use (odds ratio [OR], 3.96; P = .026),
• duration of BADK symptoms (OR, 1.05; P <.001),
• length of hospitalization during the first episode (OR, 1.07; P = .043),
• histological features of chronic active colitis (OR, 4.8; P = .025) or microscopic colitis (OR, 5.0; P = .045), and
• delay in administering selective immunosuppressive treatment for BADK (OR, 1.06; P = .047).

Regarding the use of PPİ as a risk factor for chronic BADK, the study researchers stated, "Our findings arose from the known effect of this routinely used drug class on the gut microbiota: specifically, increased risk of enteric infection, bacterial translocation and the pathogenesis of microscopic colitis (one of the histological variants of BADK)."

The most striking finding of this study was that, compared with acute BADK (33%; P = .019), patients with chronic disease (14%) had significantly lower cancer progression.

The outcomes of the 2 immunosuppressive agents used for patients with chronic BADK were surprising. Multivariable analysis showed that the use of infliximab-based treatment compared with vedolizumab (OR, 5.10; P = .004) was independently associated with cancer progression.

Regarding this finding, the study researchers stated, "Vedolizumab treatment accounted for most of the [selective immunosuppressive therapies] used in our study and may serve as a protective factor because it reduces the antitumour effect of immunotherapies less than infliximab."

In interpreting the results, the researchers described chronic BADK as "probably reflecting a prolonged immune checkpoint inhibitor effect and being associated with better cancer outcomes and overall survival".

However, they added, "future larger-scale studies are warranted to clarify the predictive value of histological features in chronic BADK and cancer treatment-related outcomes".

Related Topic:

- Immunotherapy and Cancer Vaccines