With a median age at diagnosis of 71 years, multiple myeloma is a condition that primarily affects older individuals. As is true of other hematologic malignancies, there are distinct challenges associated with management of myeloma in older individuals, who are more likely to have coexisting medical conditions and to develop chemotherapy-related toxicities, and are thus less likely to experience long-term benefits from treatment.
At the same time, it is clearly recognized that older patients are heterogeneous in terms of their health and fitness. It’s thus imperative to individualize treatment plans, and along these lines prospective assessments of fitness vs. frailty in older patients may be quite useful. Indeed, in a recent analysis by the International Myeloma Working Group, a Geriatric Assessment of frailty was predictive of both overall survival and chemotherapy-related toxicity.
Our group has been very active in the development of new agents and treatment regimens that will favorably impact the care of older patients. We collaborated with colleagues at Massachusetts General Hospital in a clinical trial evaluating a modified version of lenalidomide-bortezomib-dexamethasone (i.e., RVD) therapy with dose and schedule tailored for older individuals with newly-diagnosed myeloma. We found that with adjustments to standard RVD, chemotherapy-related toxicity could be reduced without compromising the effectiveness of the regimen.
In addition, our group has been a lead center in the development of the first oral proteasome inhibitor, ixazomib. Because of its oral administration and favorable safety profile, ixazomib is likely to be an effective treatment option for older individuals when used in combination with other agents.
Our group has also been a lead center for the development of the first monoclonal antibodies approved for use in myeloma, daratumumab and elotuzumab. The availability of these agents, which effectively partner with a variety of standard anti-myeloma drugs, will likely also have a favorable impact on the care of elderly individuals with myeloma.
Looking to the future, there is great promise associated with novel immunotherapeutic approaches in myeloma, including vaccines and checkpoint inhibitors, which stand to improve patient outcomes overall, and specifically outcomes for older individuals.