IMS 2024 | The importance of adjusting dosing when treating elderly/unfit patients with multiple myeloma

So when we, as I often say, when we treat myeloma, we don’t really treat myeloma, we treat people. And so it’s so fundamental that when we do our stratification to decide what to treat someone with, that we account for all of their factors, of which age may be one, but really it is much more about their fitness, about their frailty, than just the day they happen to be born. We have patients who are significantly younger with greater comorbidities and frailty, other older patients who actually do really quite well with minimal comorbidities. So my typical approach when I think of those patients who are older, who are more frail, who are in the historical context transplant-ineligible, I always want to remember that myeloma is actually the same disease in a different host. And recently with the two very large, now soon to be three large Phase III trials looking at older patients with myeloma, we’ve learned that quadruplets can feasibly given to these patients, at least up to the age of 80, and indeed perhaps in many patients over 80. So my approach is as follows: I like to think about the fact that we need that multi-combination approach. I would ideally like to give them all a CD38 antibody, a proteasome inhibitor, and an immunomodulatory drug with some dexamethasone. But the huge caveat is really all about the dosing. We want to leverage the mechanisms of action, but be careful in the dosing. In these trials, they had to, by convention, start at 25 milligrams of lenalidomide. Some of them started twice weekly bortezomib. Some of them gave significantly higher doses of dexamethasone. But for each of those three, I’m very rational in my approach. Most of my patients only get subcutaneous once weekly bortezomib. Most of my patients are getting 10 milligrams of lenalidomide instead of 25. And most of my patients are starting at lower dose dexamethasone, either 20 or 12, with a taper down to have that dexamethasone off within four to six months. And what I found is I can leverage the mechanisms of action together, but more feasibly, more tolerably give it to the patient so I can contribute to both their quantity and quality of life.