I have found a study of which the result of the study supports the idea that BCG + Immunotherapy (keytruda in this case) good efficacy to BCG unresposive high risk NMIBC> The study was led by Johns Hopkins and the result was published in November 2019. The collaborators for the study involves whos whos of well known urologist/researchers in the bladder cancer field. There are many parts I fully do not understand but the study had addressed many questions which point to why some patients do not respond to BCG treatment. The study had divided into two groups (cohorts). Each groups consisted of about 30 various high risk (TaHG, T1, CIS) NMIBC patients. One group consisted of BCG responders who had responded with Initial BCG induction course. The other group consisted of BCG responders who had recurrence with high risk NMNBC after the initial BCG induction course. The main result of the study was that prior to BCG induction, about 25-28% of BCG non responders had high PD-L1 expression -meaning that PD-L1 proteins were found in tumor microenvironment (environment nearby (including) tumor cells) but only 4% of BCG responders had PD-L1 expression. PD-L1 is immune check points found on cancer cells interact with PD-1 which is immune check point found on T-cells and prevent T-cells to attack the cancer cells. Immune check point inhibitors such as Keytruda are antibodies which bind to immune check points (PD-1 or PD-L1) and inhibit its interaction, and let T-cells to attack the cancer cells. The study hinted that BCG non responders should respond to BCG by inhibiting PL-D1 immune check point inhibitors and recommended a study of the treatment for BCG unresponsive high risk NMBC with immune check point inhibitors (immunotherapy) with BCG combined. Refer to the link below for the report of the study.
One point we need to consider for any treatment for NMIBC is also what urologists consider important for NMIBC is that NMIBC will not progress to muscle layer before the recurrence of high risk NMIBC is detected during the treatment because once the tumor progress to muscle layer, the chance for metastasis will increase. I remember when I watched a video of the announcement of the clinical trail for Keytruda alone for BCG unresponsive NMIBC, Dr. Arjun Balar (one of chief urologists/researchers who conducted the clinical trail) had highlighted as an important point for immunotherapy that no patients had progressed to muscle layer during the clinical test.
Thank you for the information and the links. I read both of the articles and remain optimistic on this course of treatment. Fortunately I have never encountered any side effect from BCG or Keytruda. Both have been easily tolerated. It's hard to believe how accustomed i got to cystoscopies and BCG treatments.
Congrats and thank you for posting your treatment for BCG unresponsive non muscle invasive bladder cancer. I know that Keytruda itself had already been approved by FDA for BCG unresponsive non muscle invasive bladder cancer.
It looks like it is still in the Phase III clinical trial stage. A preliminary analysis of a Phase I study showed better result than Keytruda alone for BCG unresponsive non muscle invasive bladder cancer according to the report by Dr. Ashish Kamat of MD Andersons. (refer the link below).
A preliminary analysis of a Phase I study of intravesical BCG combined with pembrolizumab in patients with high-grade NMIBC after treatment failure with at least two courses on intravesical therapy (one contains BCG) showed that the combination therapy had an overall response rate of 67% and was well tolerated with acceptable safety