Q&A: Fecal transplant appears effective for immunotherapy-induced colitis

Yinghong Wang
Yinghong Wang

Fecal microbiota transplantation may be a viable treatment option for patients with cancer who have developed immunotherapy-induced colitis, according to results of a case series published in Nature Medicine.

FMT has been shown to be effective in treating patients with Clostridium difficile infections and inflammatory bowel disease but has not previously been tested as a treatment option in patients with cancer who have developed gastrointestinal side effects as a result of their immunotherapy.

Immunotherapy-induced colitis, the second most common side effect from immune checkpoint inhibitors, occurs in up to 40% of patients with cancer, according to Yinghong Wang, MD, PhD, director of Medication Induced Colitis and Enteritis at The University of Texas MD Anderson Cancer Center.

Wang and colleagues made the decision to investigate the potential of FMT as an alternative therapy for patients suffering from refractory, or unresponsive immunotherapy-induced colitis.

Wang spoke with Healio Gastroenterology and Liver Disease about how the idea of using FMT as a treatment option came about, the effectiveness of FMT and how gastroenterologists play a role in treating these patients.

Healio: What led you and your colleagues to test the efficacy of FMT in patients with immunotherapy-induced colitis?

Wang: We have seen the urgent need to find an alternative treatment option for patients with cancer who have failed standard treatment, such as immunosuppressive therapies. We have encountered those cases and based on current knowledge we typically have nothing left to offer. We don’t want to see the patients suffer and stop their cancer treatment, and we decided we needed to think outside the box and find an alternative.

I have taken part in almost 100 cases of fecal transplant for patients with recurrent C. diff and have had great experiences in terms of efficacy situating in infections and have had minimal complication rates.

I felt very comfortable performing those procedures. The combination of the urgent need from patients’ side for the treatment solution, the promising evidence in the literature from fecal transplantation in multiple disorders and familiarity of this practice triggered me to consider exploring fecal transplantation as an alternative option.

What particularly came to my mind when I was thinking about studying this was that there were some animal studies in the past 2 years that looked at mouse models that had developed colitis secondary to immunotherapy. The researchers found that the colitis was significantly improved after the mice were fed with different bacterial combination in their diet.

Healio: How is this study different than other studies that have looked at FMT for the treatment of ulcerative colitis?

Wang: Overall, there are definitely features that overlap between ulcerative colitis and immunotherapy-induced colitis, but the underlying mechanism is somewhat different. One of the disorders is drug-induced, and one is autoimmune.

Also, the clinical, endoscopic and histological presentations are different.

For instance, immunotherapy-induced colitis has a much bigger spectrum of characteristics than ulcerative colitis. We really don’t know for sure what the disease behavior will be like long-term, is it exactly like inflammatory bowel disease or is it different. Based on our MD Anderson experience for the past 2 years since I came here, we have published approximately eight studies and we have made a good summary about the overall characteristics of immunotherapy-induced colitis.

It seems to include a much broader presentation than inflammatory bowel disease, especially ulcerative colitis. For example, immunotherapy induced colitis can overlap completely with microscopic colitis.

The literature on fecal transplants for ulcerative colitis outcomes is very controversial. We can’t really predict what the response is going to be for patients with immunotherapy-induced colitis either based on our limited knowledge.

Healio: How was the study conducted?

Wang: The first case was done in June 2017 and at that time, I was initially involved in the case because the patient had already been hospitalized for more than 1 month for persistent bleeding and diarrhea and had failed every treatment option. The patient’s oncologist was very desperate and asked me if I had any other options. I brought the idea of FMT to the patient and explained the situation that this could be the first case ever and I couldn’t guarantee the treatment effect. Instead, there could be a potential risk for complication. The patient was very open minded and agreed to pursue this treatment given all the standard options have been exhausted. Surprisingly,

the treatment turned out to have a miracle effect. We subsequently analyzed those samples and confirmed what had changed in the stool microbiome of the recipient. After seeing the promising results of that case, it really encouraged me to offer FMT to more cases. After treating more cases, I have seen pretty consistent results.

Healio: What were the limitations with the study?

Wang: There was a very limited sample size with this study. Although we had two completed cases that we published, I have completed several more cases, but patients’ follow-up evaluation took a very long time, that is why we could not include all the cases in this study.

Healio: What are the future plans to further continue the study?

Wang: With the promising result from our preliminary study, we would definitely like to offer this option to more patients who will benefit from this treatment. My goal is to start a clinical trial in our institute to offer this fecal transplant as either compassionate treatment or even first-line treatment for patients with cancer who have developed immunotherapy-induced colitis.

Healio: Why is it important for the development of newer treatment options for patients with immunotherapy-induced colitis?

Wang: We know that immune checkpoint inhibitors have become a miracle drug for many cancers.

We want patients who benefit from immune checkpoint inhibitors to stay on their treatment to completely eradicate their cancer. The limitation is that immunotherapy-induced colitis is a common side effect that delays or stops treatment.

Along with oncologists, we need to work as a team to remove this obstacle and put the patients back on their cancer treatment for as long as they need. The current treatment for this toxicity is immunosuppression, which is to reverse the immunotherapy.

Then there is a concern that by using immunosuppressive treatments for toxicity, whether the cancer treatment is going to be compromised. Based on our current knowledge, we don’t have a clear answer to this question. However, if we could offer a treatment that is not reversing the immunotherapy’s effect, it is certainly a safer choice.

Fecal transplant doesn’t have any immunosuppressive effects and has been demonstrated to be very safe in the previous studies in other fields. Additionally, there are animal and human studies that have shown that certain bacteria species in a healthy gut microbiome may provide synergistic effect to the cancer regression.

This is all telling us that stool microbiome is doing a lot more than what we could imagine, and we should take full advantage of it and not waste it.

Healio: How can gastroenterologists play a significant role in helping to better treat these patients?

Wang: These immunotherapies have been used across many different clinical trials for cancer at least for the past 10 years. But, the involvement of the gastroenterologist has not been as frequent as we might have wanted until probably the past year.

Most oncologists are familiar with those immunotherapy medications and have been the main group of physicians who manage all the toxicities. Previously, the gastroenterologist’s role was mainly to provide endoscopy evaluations instead of providing more input on the medical management.

But in the past 2 years, more gastroenterologists, especially at large cancer centers, have started to have more exposure to this disease entity and realize that our knowledge in GI field could have provided more impact on these patients’ care.

I’m confident with the group effort from gastroenterologists and oncologists, we should be able to make more progress in optimizing our quality of care to this particular medical condition.

Reference:

Wang Y, et al. Nat Med. 2018;doi:10.1038/s41591-018-0238-9.

Disclosure: Wang reports no relevant financial disclosures.

 

 

Yinghong Wang
Yinghong Wang

Fecal microbiota transplantation may be a viable treatment option for patients with cancer who have developed immunotherapy-induced colitis, according to results of a case series published in Nature Medicine.

FMT has been shown to be effective in treating patients with Clostridium difficile infections and inflammatory bowel disease but has not previously been tested as a treatment option in patients with cancer who have developed gastrointestinal side effects as a result of their immunotherapy.

Immunotherapy-induced colitis, the second most common side effect from immune checkpoint inhibitors, occurs in up to 40% of patients with cancer, according to Yinghong Wang, MD, PhD, director of Medication Induced Colitis and Enteritis at The University of Texas MD Anderson Cancer Center.

Wang and colleagues made the decision to investigate the potential of FMT as an alternative therapy for patients suffering from refractory, or unresponsive immunotherapy-induced colitis.

Wang spoke with Healio Gastroenterology and Liver Disease about how the idea of using FMT as a treatment option came about, the effectiveness of FMT and how gastroenterologists play a role in treating these patients.

Healio: What led you and your colleagues to test the efficacy of FMT in patients with immunotherapy-induced colitis?

Wang: We have seen the urgent need to find an alternative treatment option for patients with cancer who have failed standard treatment, such as immunosuppressive therapies. We have encountered those cases and based on current knowledge we typically have nothing left to offer. We don’t want to see the patients suffer and stop their cancer treatment, and we decided we needed to think outside the box and find an alternative.

I have taken part in almost 100 cases of fecal transplant for patients with recurrent C. diff and have had great experiences in terms of efficacy situating in infections and have had minimal complication rates.

I felt very comfortable performing those procedures. The combination of the urgent need from patients’ side for the treatment solution, the promising evidence in the literature from fecal transplantation in multiple disorders and familiarity of this practice triggered me to consider exploring fecal transplantation as an alternative option.

What particularly came to my mind when I was thinking about studying this was that there were some animal studies in the past 2 years that looked at mouse models that had developed colitis secondary to immunotherapy. The researchers found that the colitis was significantly improved after the mice were fed with different bacterial combination in their diet.

PAGE BREAK

Healio: How is this study different than other studies that have looked at FMT for the treatment of ulcerative colitis?

Wang: Overall, there are definitely features that overlap between ulcerative colitis and immunotherapy-induced colitis, but the underlying mechanism is somewhat different. One of the disorders is drug-induced, and one is autoimmune.

Also, the clinical, endoscopic and histological presentations are different.

For instance, immunotherapy-induced colitis has a much bigger spectrum of characteristics than ulcerative colitis. We really don’t know for sure what the disease behavior will be like long-term, is it exactly like inflammatory bowel disease or is it different. Based on our MD Anderson experience for the past 2 years since I came here, we have published approximately eight studies and we have made a good summary about the overall characteristics of immunotherapy-induced colitis.

It seems to include a much broader presentation than inflammatory bowel disease, especially ulcerative colitis. For example, immunotherapy induced colitis can overlap completely with microscopic colitis.

The literature on fecal transplants for ulcerative colitis outcomes is very controversial. We can’t really predict what the response is going to be for patients with immunotherapy-induced colitis either based on our limited knowledge.

Healio: How was the study conducted?

Wang: The first case was done in June 2017 and at that time, I was initially involved in the case because the patient had already been hospitalized for more than 1 month for persistent bleeding and diarrhea and had failed every treatment option. The patient’s oncologist was very desperate and asked me if I had any other options. I brought the idea of FMT to the patient and explained the situation that this could be the first case ever and I couldn’t guarantee the treatment effect. Instead, there could be a potential risk for complication. The patient was very open minded and agreed to pursue this treatment given all the standard options have been exhausted. Surprisingly,

the treatment turned out to have a miracle effect. We subsequently analyzed those samples and confirmed what had changed in the stool microbiome of the recipient. After seeing the promising results of that case, it really encouraged me to offer FMT to more cases. After treating more cases, I have seen pretty consistent results.

Healio: What were the limitations with the study?

Wang: There was a very limited sample size with this study. Although we had two completed cases that we published, I have completed several more cases, but patients’ follow-up evaluation took a very long time, that is why we could not include all the cases in this study.

PAGE BREAK

Healio: What are the future plans to further continue the study?

Wang: With the promising result from our preliminary study, we would definitely like to offer this option to more patients who will benefit from this treatment. My goal is to start a clinical trial in our institute to offer this fecal transplant as either compassionate treatment or even first-line treatment for patients with cancer who have developed immunotherapy-induced colitis.

Healio: Why is it important for the development of newer treatment options for patients with immunotherapy-induced colitis?

Wang: We know that immune checkpoint inhibitors have become a miracle drug for many cancers.

We want patients who benefit from immune checkpoint inhibitors to stay on their treatment to completely eradicate their cancer. The limitation is that immunotherapy-induced colitis is a common side effect that delays or stops treatment.

Along with oncologists, we need to work as a team to remove this obstacle and put the patients back on their cancer treatment for as long as they need. The current treatment for this toxicity is immunosuppression, which is to reverse the immunotherapy.

Then there is a concern that by using immunosuppressive treatments for toxicity, whether the cancer treatment is going to be compromised. Based on our current knowledge, we don’t have a clear answer to this question. However, if we could offer a treatment that is not reversing the immunotherapy’s effect, it is certainly a safer choice.

Fecal transplant doesn’t have any immunosuppressive effects and has been demonstrated to be very safe in the previous studies in other fields. Additionally, there are animal and human studies that have shown that certain bacteria species in a healthy gut microbiome may provide synergistic effect to the cancer regression.

This is all telling us that stool microbiome is doing a lot more than what we could imagine, and we should take full advantage of it and not waste it.

Healio: How can gastroenterologists play a significant role in helping to better treat these patients?

Wang: These immunotherapies have been used across many different clinical trials for cancer at least for the past 10 years. But, the involvement of the gastroenterologist has not been as frequent as we might have wanted until probably the past year.

Most oncologists are familiar with those immunotherapy medications and have been the main group of physicians who manage all the toxicities. Previously, the gastroenterologist’s role was mainly to provide endoscopy evaluations instead of providing more input on the medical management.

But in the past 2 years, more gastroenterologists, especially at large cancer centers, have started to have more exposure to this disease entity and realize that our knowledge in GI field could have provided more impact on these patients’ care.

I’m confident with the group effort from gastroenterologists and oncologists, we should be able to make more progress in optimizing our quality of care to this particular medical condition.

Reference:

Wang Y, et al. Nat Med. 2018;doi:10.1038/s41591-018-0238-9.

Disclosure: Wang reports no relevant financial disclosures.