Question:
My husband did Cryoablation for LMS on his primary tumour and we are aware of its immune (apyscopal) effects. I wanted to see whether doing chemo now a week later will wipe out the immuno effects of cryo? If yes should we use this window to do other kinds of immune therapy whether dendritic cell, PD1 or CTLA-4, or even natural immune boosting remedies. We know that single agent PD-1 doesn't seem to work for Leiyomyosarcoma. They are doing trials of double immuno however the results haven't been available so we are not sure. We are in Canada so may even do it off-label to save on costs and be closer to home. Thank you so much for your feedback!
Answer:
1) Chemo after cryoablation - It depends on what the chemotherapy is. If the chemotherapy destroys white blood cells (this includes T cells!), this could possibly negatively impact any immune activity that the cryoablation triggered (Chapter 11, starting from "We told Monica about cryoablation...", page 172)
2) What immunotherapy to do after cryoablation?
Our combination strategy post-cryo (with the treatments that were available at that time) and examples of various immunotherapy combination therapies are described in Chapter 11, "Devising a combination strategy", pages 178-184.
3) PD-1 single agent vs. double checkpoint inhibitors vs. other combinations
The section in Chapter 16, "A Tail of Survival", pages 268-272, is pertinent to your question. It explains the reason why PD-1 monotherapy results may not be spectacular, why combination immunotherapy treatments have a better response rate, and how to harness a complete immune response by layering treatments that address different aspects of the immune response (Table 3).
We wish your husband the best!
Thanks so much for the kind reply and detailed information. My husband is not qualifying for the new double immuno trials now but he has done the Cryo and I want to follow your protocol and try dendritic vaccines and T-cell therapies discussed in p. 178 onwards. Do you recommend we consult Dr. Chang's clinic in NY and Dr. Nesselhut in Germany to help us.
Checkpoint blockade and other modern immunotherapies available through clinical trials or off-label treatments are more powerful than the treatments I had access to. I would exhaust all avenues to obtain checkpoint blockade before considering dendritic vaccines. Chapter 16 section "What I would do if my cancer returns" goes into how I would leverage the immunotherapies that are available today.
You can look into obtaining PD1 (Opdivo or Keytruda) off-label from an oncologist who has experience administering checkpoint blockade.
There may also be other checkpoint blockade clinical trials for sarcoma patients -- reach out to Cancer Research Institute, they have a clinical trial finder program where someone helps you find trials.
Thank you this is very helpful as anything we do at this point will have to be off-label. I can access PD1 or other checkpoint blockade but are you saying that what Nesselhut did is not as effective as these new modern immune drugs?
We wrote about the dendritic vaccines and other immunotherapies in our book, please refer to these chapters for more information: Checkpoint blockade (Chp 7), Dendritic Vaccine (Chp 12), Adoptive T cell therapy and Peptide Vaccines (Chp 6).