Do guidelines exist to help the treating physician modify treatment based on frailty?

How is treatment for myeloma modified for patients who are frail? A patient who may be frail, some of the key things is first you need to ask yourself, what is this patient's preferences? What is this patient's goals? These are really, really important. The reason being is that myeloma being the disease that tends to be incurable but yet manageable, there are several treatments that we have available, but some of them or most of them will have some form of treatment-related toxicity. In the frail patient, the fear there is that these patients have an increased risk of actually getting higher grade toxicities, so more severe toxicities that can be quite debilitating in some instances. And so when you're frail, the idea is that you're not treating that patient with trying to get them into the deepest remission for their myeloma, but rather the treatment goals are really to make sure that whatever symptoms they may or may not be experiencing, that we're actually offering more of a palliative. So our goal at that point is to really treat for quality of life benefit rather than to treat for maximum efficacy for a treatment for myeloma. So ways in which we can modify treatments is that we can first start to think about how many drugs are we offering patients. So in a person who is fit, now there are four drugs that patients get, three drugs, but a frail patient, we may not want to start with three drugs because we are concerned that there is a potential added risk of toxicity. So we may start with two drugs. And then the other thing that we may want to do with those patients is we may want to upfront dose adjust or reduce the dose of some of the medications. So a perfect example of that is something called lenalidomide, which is a common drug used in the treatment of myeloma. And so in a frail adult, whereas a starting dose may be 25 milligrams for a patient who has normal kidney function, a frail adult, we may want to start at 15 milligrams or even 10 milligrams. And then the idea is that you want to start low and go slow, which is a geriatrics thinking, way of thinking for escalation of therapy, because we want to see if that patient is able to tolerate the drug that you're giving them. So in essence, when you have a patient who is frail, the key things that you want to think about are patient goals and patient preferences, quality of life for the patient, remembering that you're not going to be able to cure this patient or give them maximum therapy to keep them in remission, the deepest remission, or to achieve a best response. But you really want to make sure that whatever symptoms this patient is having, that you are managing those with palliative care and that your interventions, your anti-myeloma therapies are sufficient enough to control symptoms, but not add new symptom burden to that patient that will ultimately lead to worsening up their quality of life. Is there a study which shows that if a patient reduces the dose, they can stay on treatment longer and have a better outcome? I'm not able to recall the study exactly, but that is generally the thinking because as I mentioned before, this risk of over-treatment of older adults is definitely there, especially those who are frail. And when you over-treat these adults, then what ends up happening is that patients oftentimes they have to discontinue their treatments early because they develop significant toxicities. And so there is then this period where there are no therapy whatsoever, rather than, you know, if you start low, you go slow, then you will be able to, in most cases, keep patients on treatments longer because you are actively titrating the medication in accordance to how that patient is going. So I definitely believe that you're on the right track in terms of thinking about, you know, whether or not a patient who is frail will stay on treatment longer or discontinue treatment earlier if we expose them to more intensive therapies. What does start low and go slow mean? The idea behind start low and start and go slow is the next step, which is but keep going. And so if you put it all together, you start at a low dose of the treatment, you monitor the patient for toxicities, and in this case, we use our frillty scores to see whether or not a patient's fitness level continues to improve. And then with improvements in their fitness level or increased tolerance to the particular then you can increase up or escalate the dose of that therapy to whatever is the standard dosing that would be used. Or you can, you know, keep it at a dose in which the patient is tolerating and which you're benefiting in terms of maximum efficacy. So even though as oncologists and hematologists, sometimes our thinking is that we see a patient, our first instinct is that we really need to get this patient on maximum dose therapy right away. But really, there is a lot of flexibility around what we're able to do, especially in our frill patients, as long as they're not in a clinical trial in which everything is set out for you in terms of a protocol. So in real life, it really is about what is this patient able to tolerate and what is the disease doing. And so that brings me to two other concepts that we think about. And we always think about when we're thinking about treatment in the older adult patient is you need to stage the aging as well as stage the malignancy. So in this case, you're staging their myeloma. So you're thinking about what their disease biology is like, how aggressive the disease is likely to be. But at the same time, you need to also consider what else is happening and contributing to the aging of this person before you. Definitely in terms of the role that care partners play in the care of multiple myeloma, it is very important for care partners to remain vigilant as their loved ones are being treated. And sometimes the patients may not bring up whether or not they're having toxicities. But at the point where the care partner may notice that there are things that are significantly different, that is where we want to encourage them to have that open conversation with the treating oncologists and hematologists.