There is a delayed effect of immunotherapy

  A series of successes in clinical trials of tumor immunotherapy have made it a hot treatment in oncology, recognized by more and more clinicians and widely used in the treatment of many malignancies. In particular, it was named as one of the top ten discoveries in the world in 2013.  Since tumor immunotherapy targets the improvement of patient’s immune system to kill tumor cells through the immune system, it is different from traditional tumor treatment methods, such as surgery, radiotherapy and chemotherapy which mainly target to reduce tumor load. Unlike chemotherapy, the short-term increase in tumor load after tumor immunotherapy is not necessarily due to tumor growth, but may also be due to temporary immune cell infiltration, which often occurs prior to the onset of significant antitumor effects; in addition, the appearance of new lesions may also arise from a local inflammatory response due to massive T lymphocyte infiltration in tiny tumor foci that were previously undetectable by imaging. .  For example, in 2013, at the International Congress on Cellular Therapy (ISCT) in New Zealand, a clinical trial of DC vaccine for the treatment of glioma reported that patients had a tendency for tumors to increase in size before they tended to shrink after about 230 days of treatment after 8 doses of DC vaccine. There is also the experience from Tremelimumab and Ipilimumab. The initial ownership of CTLA-4 monoclonal antibody was Medarex in the US, which started phase I and II clinical trials in 2000, showing an efficiency of nearly 10% in advanced malignant melanoma, followed by a number of major pharmaceutical companies expressing interest in CTLA-4 monoclonal antibody. In the Phase III trial of Tremelimumab, an early interim analysis based on chemotherapy drug-related criteria found no improved survival benefit and terminated the Phase III trial of Tremelimumab, but two years later, a follow-up analysis of the enrolled population showed that Tremelimumab improved overall survival. Lessons were learned during the development of Ipilimumab, changing the endpoint evaluation metric for the phase III clinical trial to overall survival and eliminating the interim analysis because the analysis at earlier time points could have misled survival assessment, and the final phase III clinical trial results did show a survival benefit with Ipilimumab for melanoma patients.  Therefore, clinical attention should be paid to the delayed effect of immunotherapy and lagging assessment of efficacy.