Induction Therapy for Myeloma

Transcript: Paul G. Richardson, MD: Let’s move on to our next point of discussion, and it dovetails very nicely into just what we concluded with, of the individualized induction therapy for when a patient has truly active myeloma. I’m going to ask Ken to lead this part of the discussion please.

Kenneth H. Shain, MD, PhD: One of the things we were just talking about is obviously giving therapy early to smoldering patients, sometimes who have active disease requiring therapy or have met criteria for active disease. We want to make sure we’re thinking about the therapies we have today that allow us to give excellent therapy, high quality therapy, deep responses, etc, with maximizing quality of life. Now we have a lot of studies that are saying maybe 3 drugs are obviously better than 2, triplets are the way we think about things; quadruplets are something we’re working on these days in terms of therapies.

But how do we start individualizing this and who gets full doses, who needs triplets versus quadruplets? The thing about our patient population is that they’re not all young, healthy, transplant-eligible individuals. Most of our patients are going to be elderly, and not be quite as fit or ready for transplant or high-dose therapy, or even multi-drug combinations up front.

So we have to start thinking about how we can better parse those individuals to give them individualized care. Is that just going to be based on frailty scores, because elderly patients have a bit higher risk or poor outcomes, generally speaking.

If we tailor these therapies a little better and our frailty score is the answer, I think we have obviously several that are being utilized in ways to help us try to identify and stratify our patients to help us then give the right amount of drugs, maybe not necessarily fewer drugs, but the right amounts of drugs. I think that’s a really important thing that if we can say, “We need these 3 mechanisms of action or 4 mechanisms of action; can we give the right amount to our patients?”

Having those become incorporated into our decision making is going to be critical. I think the same theme kind of follows through as we as clinicians have an eye for what might be a frail, fit/unfit patient. These scores are there to help us hopefully do a little better, but it would have to be simple because we are physicians and we can’t spend a lot of time thinking too much, right? I mean the 20/2/20 criteria is a great way to think about this; adding scores and those things are very difficult for us to work on.

Those are things that we have to think about working into our balance in terms of how to take care of therapy. In our clinic you have to think of those things. We’re in Florida, so Moffitt Cancer Center is a place where the elderly patient population is somewhat enriched here. Those are the things we think about every day when we see our patients. It really is, how can we make sure we utilize that kind of stratification, individualizing care for patients? A 79-year-old who walks in who plays golf every day might get different doses than a 79-year-old who can’t play every day. Those are the things you have to think about. It’s the same 3 drugs, maybe it’s a different dosing strategy for each of those things. A lot of data have told us how we can maybe better give and deliver these drugs, it’s not all the same way. That’s how I think we have to start.

Paul G. Richardson, MD: Ken, do you actually do a frailty score, or do you sort of say look, to your point, this is a very common sense view, you have a 79-year-old patient who’s an avid golfer and has got an excellent BMI [body mass index] and is in great shape and has no comorbidities? Or do you actually follow the guidelines that are available?

Kenneth H. Shain, MD, PhD: What we do right now is essentially, it is more of a physician-specific kind of way. I have found it very difficult to put those things in a clinically useful, practical way, which is part of the big issue. Can we please find a way to do this in a more simplistic way?

Now we have trials built around the elderly population. We have a number of trials, where we’re…a risk-response adapted approach. But that is built into it. You can figure out who are those patients who really need, we can identify as individuals who fall into frail or fit, based on these risk stratification stories. So something we do in trial but not currently in practice.

Paul G. Richardson, MD: Nina, please.

Nina Shah, MD: Sonja Zweegman MD did present the data for unfit and frail myeloma using an ixazomib-based regimen. First of all, I love the trial because it’s a hard thing to do. What I thought was interesting is the people who were unfit did a little bit differently than the people who are frail. What that means to me is our scoring is not consistent for these. If we’re going to do trials with these, then we should be able to have consistent scoring. Just like with the smoldering risk adaptation, you have to know how your scoring is consistent or not. That really struck out to me.

What’s so great now is we have a lot of trials in transplant “ineligible,” understanding that doesn’t always mean unfit. We all know how to dose modify. So RVd [lenalidomide, bortezomib, dexamethasone]-Lite, things like that, are important to consider. Some people want to get therapy but they also recognize their own limitations. So a lot of patient discussion, physicians understanding gestalt, I think goes into it.

Paul G. Richardson, MD: Ajai, how do you take on this issue?

Ajai Chari, MD: I think we accept ISS [International Staging System], FISH [fluorescence in situ hybridization] as risk stratification. The frailty I think because it’s not a quick, 1 second thing. There was a recent Blood publication that showed that probably the single best test is your gait speed. We have a patient on a clinical trial who had a lot of complications. She had the worst gait speed of anyone enrolled. I think that’s a quick, it’s kind of an eyeball thing, but you have the patient get up and walk. And how long that takes, it can be done in 20 seconds. That I think is going to be important, and if we don’t stratify clinical trials by these kinds of patients, recognizing though that even in a gait-speed adjusted, who’s getting into a study; real-world patients, probably at best, 50% of real-world patients are eligible for studies. I really want to echo what Ken said which is, it’s not the number of drugs, it’s the doses and schedule. Everybody needs rapid responses to treatment. It’s just in a deliverable fashion. I think it’s not to sacrifice on a number of drugs, but the doses and schedules, and also the monoclonal antibodies in particular; very well tolerated as a triplet in elderly.

Paul G. Richardson, MD: It’s incredibly important to recognize that the performance status gait speed and the symptoms are of course driven by disease. An effective regimen can then transform that in a way that obviously you can see a dramatic improvement. Sagar if I may, your thoughts on this.

Sagar Lonial, MD, FACP: I think the reality is that much of what you guys are describing is

not captured anywhere in our medical record. It really requires you to spend time trying to understand. I actually ask the 75-year-old guy, “Do you play golf? What do you do during a day? How’s it different now than it was 3 months ago?” I think those kinds of things are often missed, and they’re not in any of the 6-page, content-free notes that we sometimes get.

Amrita Y. Krishnan, MD: I would make the comment that myeloma is a little different than other diseases because often when patients present they have a lot of compression fractures, bony disease, which in one sense really acutely decreases their performance status. You don’t want to underestimate their true performance status.

The other thing I would say in terms of gait speed also, my gait speed from day 1 at ASH [American Society of Hematology 2019 annual meeting] greatly diminished by day 4.

Paul G. Richardson, MD: Hopefully you don’t need treatment.

Transcript Edited for Clarity