Treatment Options for Relapsed/Refractory Multiple Myeloma and Palliative Support

Jatin Shah, MD: When we think about relapsed or refractory myeloma, when the disease first comes back or comes back subsequently, it’s important to think about how we treat those patients at that point in time. There are multiple factors that go into that, both from patient specific, as well as disease specific and treatment specific. So how do they respond to their previous therapy? Do they have side effects to their previous therapy? Do they have toxicity? And once they got that, how long was their disease control, and how’s the patient doing now from their patient-specific factors as well as from, do they have hypertension or diabetes or infectious complications? It’s important to look at all those factors.

But, importantly, one of the things that we often have historically done is the concept of retreatment. So if I gave a combination that worked, the patient went into a nice remission, now more than 6 months later, so there’s durable benefit, now, they’re a year out and their disease comes back, and one of the things that we’ve historically done is retreatment. I think it’s an important option that we use, which I think, again, different than we see in other tumor types where we typically don’t retreat or reuse a previous therapeutic. In a myeloma we do that, and I think that’s based on two things.

Number one is activity that we see about previous combination; and number two with limited therapeutic options, we want to use and maximize each one of these combinations. So I think, historically, retreatment has been an important option for patients. However, I think, again, the paradigm is shifting. And the paradigm is shifting because we have multiple options for our patients, so we’re not just limited to just what we had in front-line therapy. So now there are more new options available in relapsed/refractory myeloma, and better options potentially. And so, for example, one of the things that we see is bortezomib used up front and the disease relapses, and then you want to consider using bortezomib, again. I think that’s very reasonable historically when we do not have additional therapeutic options.

But now, for example, based on the ENDEAVOR Study, where we showed superiority of carfilzomib over bortezomib when they compared that to a head-to-head trial, with improvements in response rates and doubling of the progression-free survival and doubling the CR rate, in that setting, one can think of saying, I want to use bortezomib again. However, if we look at the data, we would suggest using carfilzomib in the setting because, again, in a head-to-head phase III study, it had superior outcomes for patients. So I think that the paradigm is shifting where we thought about retreatment, but now as we move forward in the earlier relapse to therapy, we need to look at the data and look at our new options, including drugs like elotuzumab and lenalidomide and dexamethasone, including daratumumab.

So I think that though we, historically, thought about retreatment, both in first or second and third relapse and recycling drugs and putting them in combinations together, I think there’s multiple new options now where that is I think an important option; but, I think there are multiple other options that may be potentially better as opposed to just simply retreating.

It’s important when we talk about myeloma to really understand beyond just the effect of the disease and treating the cancer and dealing with the side effects, that there’s multiple sequelae of a disease that we’ll see. And we’ll see things like renal dysfunction or hyperuricemia. We’ll see infectious complications which are unique to myeloma, or bone-related fractures or bone-related pain or neuropathic pain. So, it’s important, when we start thinking about our myeloma patients, to have a global perspective and an entire healthcare team that goes around the myeloma patient—really have a multidisciplinary approach.

So, when we think about that, it’s important to have a good pain physician onboard, good access to a nephrologist to help with managing renal dysfunction, and dealing with endocrinologists with a potential diabetes or osteopenia or osteoporosis, having a good dentist onboard to help deal with potential complications from diphosphonate therapies. So, really, there’s multiple organs that are involved in myeloma, as well as multiple physicians, I think, or a healthcare system that needs to be in place when you talk about myeloma patients really to optimize their quality of life.