I was a bit concerned about repeating BCG after you had experienced with reactive arthritis (REA) as autoimmune immune disease such as rheumatoid arthritis (RA) is contraindication of BCG treatment as RA are often are being treated with immunosuppression. But, apparently REA and RA are different in such that REA is triggered by a bacterial infection, particularly of the genitourinary (2-4%) or gastrointestinal (GI) tract, (0-15%) and rare cases by Intravesical BCG. A study on REA by Intravesical BCG (iBCG) was published in 2022 by University of Kochi Rheumatolog team in japan. The study shows about 2%, 5.6%, 0.5% of Intravesical BCG patients are diagnose with REA in Japan, Europe and North America respectively. With regard to the immunopathogenesis of REA after iBCG therapy, it has been shown that iBCG therapy can provoke a systemic hypersensitivity reaction (both CD4+ (helper) and CD8+ (Killer) T cells) in addition to the previously discussed local immunity. Therefore, activated and memory immune cells may translocate to joints, resulting in the development of arthritis. The paper says the first treatment action should be the discontinuation of iBCG therapy until the complete resolution of symptoms, and a benefit-risk assessment must be conducted before resuming iBCG treatment. I am hoping that the REA you experienced was one time thing.
Fig. Hypothetical mechanism of action of iBCG causing REA. Note that our immune system responds to fragments of BCG bacteria or full bacteria equally as pathogens. a) Immune cells such as Macrophage engulf BCG bacteria and reaches to joints and/or b) bits of BCG bacteria reaches to joints and immune system responds to bits of BCG as pathogen, and/or primed T cells for BCG bacteria attack cells in joints.
Gem/doc chemo has shown to be effective. The treatment was developed by University of Iowa team with Dr. Michael O'Donnell who is considered as a GURU for treatment for NMIBC along with Dr. Lamm of University of Arizona.
Repeat BCG induction remains an option for select non-muscle invasive bladder cancer (NMIBC) patients who fail initial therapy. Alternative salvage intravesical regimens such as Gemcitabine and Docetaxel (Gem/Doce) have been investigated. the adjusted 1- and 2-year RFS was 61% and 53% after BCG/IFN versus 68% and 46% after Gem/Doc. Note that MERCK dropped Interferon (IFN) business, so BCG/IFN is no longer available. Instead, there are several treatment for BCG Unresponsive now., including CG0070.
Incidentally, GEM/DOC showed very high efficacy for BCG naïve patients according to recent retrospective study by University of Iowa team. 92% at 6 months, 85% at 12 months, and 81% at 24 months which were better than BCG group with 76% )at 6 months, 71% at 12 months, and 69% at 24 months.
It is good that you are being treated academic hospital like Moffitt as GEM/DOC are not usually not offered in community hospitals as it is too much work for them. Also, I am pretty sure GEM/DOC will not cause REA because GEM/DOC stop cancer cells from dividing (growing) by inhibiting uncoiling of DNA and disrupting of formation of microtubules before cell division, which leads to cell death. GEM/DOC does not depend on our immune system to kill cancer cells whereas BCG treatment depends, and this immune response caused REA.
CG Oncology Inc. who developed CG0070 announced Phase 2 clinical trial (18 patients) of the combination of CG0070 + immunotherpay - pembrolizumag (Keytruda) by Merck with better efficacy than CG0070 alone. 89% achieved complete response rate at 3 months. Of those achieved CR at 3 months , 85%,78%, 75% maintained CR at 6 months, 9 months, 12 months respectively. So, perhaps better to join the clinical trial of CG0700 + Keytruda than getting CG0700 alone if you consider to have CG0070 treatment in future, which I hope unnecessary to you. Below are the links to related studies
Incidentally I go to a local community hospital. The first priority of nurses at recovery room is to get patients asap to secure beds for next patients. One time, after TURBT, I could not walk straight because I chose spinal anesthesia, still the nurse wanted to be released, so I had to act like falling down to get another 2 hours of stay in the hospital. 2 hours bed for BCG sounds very envious.
REA by iBCG
GEM/DOC for BCG Unresponsive
GEM/DOC for BCG Naïve
Interim results of Phase 2 CG0070 + Keytruda for BCG unresponsive