Our good friend, MMB lifestyle columnist, Danny Parker, shared some important information about what causes multiple myeloma relapses last week. Did you see it? Probably not; it was buried at the end of a dozen comments. So let’s take another look:
His response: “Probably part disease-related (i.e. myeloma acquiring new mutations) and part host related (i.e. decrease in immunity).”
To me there are implications for both these observations.
1) To slow myeloma progress toward mutations, IMiDs (such as Revlimid and Pomalyst) likely help as they slow down immune system activity and likely slow the mutation-related activity as well. There was recent work suggesting that too low a dosage of IMiDs may help myeloma to mutate with high risk disease, one reason I have chosen to stay with Rev 10 mg/day with breaks rather than 5 mg/day continuous.
2) Decrease in immunity: IMiDs seem to help this way too. There is evidence that lenalidomide (Revlimid) enhances the activity of our T-cells that can help to attack myeloma.
Finally, the IMiDs also have strong anti-angiogenic properties and limit new blood vessel growth that can feed existing tumors.
One possible downside of the strong activity of the thalidomide derivatives in the marrow is that they may eventually encourage extramedullary tumors (plasmacytomas).
This is still under investigation.
There is also this an important new study suggesting that we need to find a way to target two genes (IRE1 and XBP1) that modulate response to the proteasome inhibitor Velcade and the mechanism underlying the drug resistance. If that could be done, we would not be able to cure myeloma, but at least we could hold it at bay as a chronic disease.
Finally, as suggested by the latter study, a cure won’t be possible until we can find a way to reach very low levels of MRD, which is why I believe a combination therapy, perhaps including Daratumumab and Elotuzumab to target both the new CS1 and CD38 antigens along with an IMiD and proteasome inhibitor could be part of the the magic potion.
Worth looking into.
Thanks, Danny! But I can’t help thinking that what Danny sees as a positive, “slowing down immune system activity,” is a double-edged sword. After all, IMiDs suppressed immunity may work against us too, allowing myeloma to advance unchecked.
I’m constantly amazed by how little researcher’s sometimes understand about how many of the meds they give us work. Scary if you think about it too carefully!
Feel good and keep smiling! Pat