Nature sub-journal: Supplementing intestinal flora may improve the efficacy of immunotherapy!

*Read only for medical professionals Reference Is the gut microbiome so magical? Renal cell carcinoma (RCC) is one of the common malignant tumors in the urinary system, and its incidence is increasing year by year
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Since nivolumab was approved by the US FDA as a second-line drug for the treatment of advanced RCC with the CheckMate 025 study in 2015, immunotherapy has made successive breakthroughs in the treatment of advanced renal cancer
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Recently, the internationally renowned medical journal Nature Medicine published a study exploring the effect of bifidobacteria supplements (CBM588) on the efficacy of RCC immunotherapy.
The clinical significance and impact of this study were interpreted and analyzed
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Immunotherapy is becoming more and more widely used in the field of RCC treatment Q medical community: How is the current performance of immunotherapy in the field of renal cancer treatment? Professor Zhang Hailiang: The role of immunotherapy in the treatment of RCC is becoming more and more important.
In 2015, based on the results of the CheckMate 025 study, the US Food and Drug Administration (FDA) approved nivolumab for the second-line treatment of advanced RCC
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With the publication of the results of CheckMate 214, KEYNOTE 426, JAVELIN Renal 101, CheckMate 9ER, and CLEAR, a variety of immunotherapy drug combinations have been approved for first-line treatment of advanced RCC
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Immunotherapy is not only suitable for patients with advanced RCC, but can also be used for adjuvant therapy after radical surgery for RCC.
The KEYNOTE 564 study showed that pembrolizumab was used after partial or whole nephrectomy with moderate to high/high Adjuvant therapy for RCC patients at risk of recurrence can significantly reduce the risk of recurrence by 32%
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Therefore, immunotherapy has gradually gained a place in the field of RCC treatment
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It is believed that in the future, the application of immunotherapy in the field of RCC treatment will definitely become more and more extensive
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Supplementation of probiotics may improve the efficacy of immunotherapy Q medical community: Could you please describe the findings of this study? What are the implications of the results of this study for clinical practice in my country? Prof.
Zhang Hailiang: This study is a phase I clinical study comparing the efficacy of nivolumab and ipilimumab with or without bifidobacteria supplementation (CBM588) in the treatment of patients with metastatic RCC
.

From its findings, patients treated with CBM588 had significantly longer PFS (12.
7 months vs.
2.
5 months, HR 0.
15, 95%CI 0.
05-0.
47, P=0.
001)
.

At the same time, the remission rate of patients who received CBM588 treatment was also higher than that of patients who did not receive CBM588 treatment (58% vs.
20%, P=0.
06), but unfortunately, due to the small sample size of the study, the remission rate was different between the two groups of patients Not statistically significant
.

It can be seen from the results of this study that bifidobacteria may improve the overall efficacy of immunotherapy, especially double immunotherapy regimens
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In the future, supplementing probiotics for patients receiving immunotherapy may be an adjuvant therapy for clinical immunotherapy
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But this needs to be confirmed by larger, higher-level studies
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At the same time, whether some patients who have failed immunotherapy can benefit from probiotic supplementation remains to be proved by relevant studies
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Pioneering clinical research Q medical community: What is novel about this research? Professor Zhang Hailiang: There are two unique aspects of this study.
First, there are more and more studies and evidences about the ability of gut microbes to improve the efficacy of immunotherapy, and some studies have pointed out that not only in RCC, but also in lung cancer and digestive tract cancer.
As well as in the immunotherapy of malignant melanoma, the intestinal flora can have a certain impact on the efficacy of patients
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This study is the first randomized controlled clinical study to explore the effect of bifidobacteria on the efficacy of RCC immunotherapy.

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Second, in addition to exploring the effect of bifidobacteria on the efficacy of immunotherapy in RCC patients, this study also conducted a relatively comprehensive accompanying study, including the levels of related cytokines or biomarkers in the peripheral blood of patients, and the abundance of bifidobacteria.
These can provide side evidence support for the research results
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How and how to maximize the benefit of the gut microbiota still needs further research Q medical community: what can be optimized in this research? What other questions need further exploration? Professor Zhang Hailiang: The research can be published in nature medicine, which has demonstrated its research value
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If you are critical of some areas to be improved or upgraded, the main points are as follows: 1.
Expand the sample size of the study
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This study is a phase I study, including 30 patients, of which 29 patients can be evaluated for efficacy, so the sample size of the study needs to be further expanded
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In the future, if relevant Phase IIb or III clinical studies are conducted and positive results are obtained, the relevant guidelines will be rewritten and the clinical practice of immunotherapy will be changed
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2.
Dosage and time of administration
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The regret of this study is that the dose of CBM588 has not been identified, and the optimal dose of CBM588 is currently unknown.
At the same time, because CBM588 is a bifidobacteria supplement, it is difficult to obtain its pharmacokinetic data clinically.
Therefore, further exploration is needed for the optimal administration time
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3.
Re-challenge treatment
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This study preliminarily demonstrated that CBM588 can further improve the efficacy of patients receiving immunotherapy for the first time, but it is also worthwhile for clinicians to study whether patients who have failed immunotherapy can be challenged with CBM588 to reverse the resistance of patients
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4.
Explore other probiotics
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This study explored the impact of bifidobacteria on immunotherapy, as the human gut microbiome is known to be diverse and complex
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In addition to bifidobacteria, whether other human gut microbes can also affect the efficacy of immunotherapy in patients, the effect of combined use of different gut microbial supplements on the efficacy, and which gut microbes can play a positive role and which can have a negative impact.
Take relevant clinicians to further explore and verify
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Overall, this study is a very comprehensive, excellent and innovative clinical study, which is very worthy of reference for relevant workers, and also has great enlightenment for future clinical research
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Expert Profile Professor Zhang Hailiang Chief Physician and Doctoral Supervisor of Urology Department of Fudan University Affiliated Cancer Hospital Deputy Head of Minimally Invasive Urology Group of China Anti-Cancer Association Member of Genetic Tumor Collaborative Group of China Anti-Cancer Association Director of Shanghai Anti-Cancer Association In recent years, domestic and foreign academic journals He has published 77 papers, including 52 SCI journal papers, and a single paper has been cited more than 350 times by other researches
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As the project leader, he presided over 1 National Natural Science Foundation of China project, and participated in 1 general project of Shanghai Natural Science Foundation as an academic backbone.
Participated in 1 basic research key project of Shanghai Science and Technology Commission and 1 joint research project of important diseases in Shanghai health system, which was awarded by Shanghai 1 first prize of Science and Technology Progress Award, 1 first prize of Ministry of Education Science and Technology Progress Award, 1 second prize of Chinese Medical Science and Technology Award Participated in and won 1 first prize of National Science and Technology Progress Award.
International Journal of Urology", "Oncology Letters", "International Journal of Oncology" and other SCI journals special reviewer