A. Keith Stewart, MB, ChB: The most important prognostic factors in myeloma relate to both the age of the patient and the genetic underpinnings of the disease. We tend to measure a patient’s frailty in terms of how fit they are to undergo therapy, such as autologous stem cell transplant. We don’t use a specific age cutoff, although around the age of 74 or 75 tends to be the transition point beyond which we feel uncomfortable applying high-dosage chemotherapy in transplant.
Beyond age, we look to other comorbidities—presence of peripheral neuropathy, cardiac disease, diabetes, all of which influence our choice of initial therapy. The most significant biomarkers that we can use for progression include blood tests such as the beta-2 microglobulin, which, when elevated, indicates a pure prognosis. Beyond that, we tend to rely on genetic testing—GI testing usually performed by a FISH analysis, or florescence in situ hybridization. It can identify 8 different forms of myeloma, some of which are high-risk and some of which are low-risk.
We usually apply those parameters mostly to the younger, fit, healthy patients when deciding how aggressive to be with treatment. In the older more frail patient, we tend to favor a more continuous therapy approach, which is less dependent on those prognostic features and more dependent on comorbidities. In those patients, use of convenient, oral, and well-tolerated regimens is favored, such as the use of lenalidomide and dexamethasone, and perhaps with the addition of bortezomib in patients who can tolerate a weekly injection.
Because of the increasing cost of drugs, the convenience of using them—particularly for patients who live far from the hospital—and the need to strategize dependent on genetic risk of the patient, we do have to do some planning when we start therapy, which looks at whether we should use all the drugs early and quickly or stagger them, or what we call sequence those different agents, over time.
So, we do start out with a definite plan in place for our younger, healthier patients, which is usually to use all our best drugs as quickly as we can. We believe we may even be able to cure some patients if we do that, and we are aggressive enough and give therapy for long enough.
For our younger patient, it would be very common to receive 3 drugs for 4 or 5 months and have an autologous stem cell transplant, perhaps some consolidation, and then maintenance therapy over many years with low levels of drugs that are given conveniently through an oral administration. In those patients, we are using all our best agents in combination early, but we already have a plan in place should they relapse, in which we have second-line drugs available to us.
In a more elderly frail patient, I think we are more inclined to be conservative in the choice of drugs that we use. We are often more interested in quality of life than longevity in that situation, and we will tend to use our most convenient, best tolerated drugs, as long as they’re still fairly effective early on, and perhaps save some of the more toxic inconvenient drugs for later in their disease course. We do know that almost all myeloma patients will relapse at some point, so we do have to have a strategy for both initial treatment and relapse.