NF-kappaB, inflammation, smoldering myeloma

Dr. R was recently interviewed on mPatient Myeloma Radio. You can find the recorded interview and transcript here:

mPatient Myeloma Radio: Where are we headed with new agents and transplant approaches in myeloma? Dr. Paul Richardson, MD, Dana-Farber Cancer Institute

I highlighted this part of the conversation because the discussion shifts to management of smoldering myeloma, including information about the mind/body program that I completed at Mass General!

Jenny: And is it something that could be used as preventative whether, let’s say, you’re in a state of remission or at a smoldering stage? I know it’s being thought about in smoldering, but even in the state of being in remission. I know patients don’t really care for the watch and wait kind of approach. They want to feel like they’re being proactive.

Dr. R: Well, I completely agree with you and I think that my patients know in my smoldering practice we’ve always tended to be proactive. We’ve looked at all sorts of various strategies. If anybody has a sniff of osteopenia, I’ve always been in favor of going after that with bisphosphonates. Interestingly bisphosphonates aren’t just bone strengtheners. These patients may or may not know they do much more than that. They have anti-myeloma effects. They also have effects on certain components of immune system including T cells. So there’s a sort of rationale to bisphosphonate use that perhaps goes beyond just simply bone strengthening but the fact of the matter is that early intervention in smoldering disease beyond simply watchful waiting is becoming a very important and active area of research.

In our own program we have a fantastic vaccine strategy that’s being developed in this area and this immunotherapeutic approach is here and have been developed by a number of colleagues and my colleague, Dr. Nikhil Munshi, has been exploring this. Also, we have as well that, the building on the platform of lenalidomide with the addition of elotuzumab. That’s another program we’re moving forward with, and my colleague Dr. Irene Ghobrial, will be hopefully taking that further as we go down the road. And in the same context actually, at a much different level, Jacob, my partner is a leading a mind-body study in partnership with the Mass General where we us simple mind-body techniques and relaxation, and sort of holistic approaches to try, and reduce inflammation and improve lifestyle strategies to reduce the risk of disease progression.

I mean that may sound incredibly fanciful but it’s actually not because what we’ve found is that with certain techniques and strategies you can reduce inflammatory signaling through this very interesting immunological access that does appear to have a strong endocrine and emotional base. And in collaboration with our colleague, Herb Benson, at the Mind Body Institute at Mass General, we’re looking at this as a real strategy. So there are a number of really interesting avenues where people can be doing more than watchful waiting, if you see what I mean Jenny.

Jenny: I think it’s terrific and I would love to learn more about that approach. Emotion does cause inflammation, so I could see a big connection with that. Well, that will be interesting to see.

Dr. R: Yeah, it’s actually quite interesting because what we did was, in a normal volunteer study, they used relaxation techniques and looked at the expression of inflammatory markers and what we found is that with specific relaxation techniques, downregulation of inflammatory markers could be achieved. And one very important clue emerged with an important switchboard that’s relevant to the biology of myeloma and that’s NF-kappaB. And what that was shown to do was be downregulated by using these mind-body strategies, and NF-kappaB is a very key switchboard to myeloma.

So that in a nutshell is the hypothesis behind this ten-week program that we’re doing. So there’s range of approaches. I must say I think it’s not going to be one. I think it’s going to be all of them put together that will give us the best outcomes but that’s how I would see it, yes.

Jenny: Well, that is great that you’re thinking about other aspects that affect those markers because I’ve heard about NF-kappaB quite a few times as being a really important pathway.

Dr. R: It is but I think the other point is that in managing this disease, a very holistic approach is relevant because we you recognize quality of life really matters and side effects are cumulative as well as potentially long-term. So this kind of multifaceted, multidisciplinary approach to disease management is really essential.

This is link describes the results of the initial research of the effects of the  relaxation response:

Study identifies genes, pathways altered during relaxation response practice

Relaxation Response Induces Temporal Transcriptome Changes in Energy Metabolism, Insulin Secretion and Inflammatory Pathways