Multiple myeloma relapse is particularly frequent in older adults due to a combination of biological, treatment-related, and patient-specific factors that interplay to make disease control more challenging over time. Understanding why relapse happens often in this population requires looking at the nature of the disease, the aging immune system, treatment limitations, and the complexity of managing older patients.
Multiple myeloma is a cancer of plasma cells, which are immune cells that produce antibodies. It primarily affects older adults, with the median age at diagnosis around 69 years. Because it is a disease of the elderly, many patients already have age-related declines in organ function and immune system strength when diagnosed. This weakened immune environment can allow residual cancer cells to survive initial treatment and later regrow, causing relapse.
One key reason relapse is frequent is the presence of high-risk disease features that are more common or more impactful in older patients. These include genetic abnormalities in the myeloma cells, such as certain chromosomal changes, which make the cancer more aggressive and less responsive to therapy. Older adults often have a higher burden of these adverse cytogenetic abnormalities, which contribute to early and frequent relapse.
Treatment options for older adults are often limited by their overall health and ability to tolerate aggressive therapies. Many older patients have other chronic health conditions, reduced kidney function, or frailty, which restrict the use of high-dose chemotherapy and stem cell transplantation—the most effective treatments for achieving deep remission. Instead, they may receive less intensive regimens that control the disease but do not eradicate it completely. This incomplete eradication leaves behind residual myeloma cells that can later cause relapse.
Furthermore, the immune system in older adults is less robust and less capable of mounting an effective anti-cancer response. This immunosenescence means that even newer immunotherapies, such as monoclonal antibodies or CAR-T cell therapies, may be less effective or have shorter durability in older patients. The immune exhaustion and tumor microenvironment factors in aging can allow myeloma cells to evade immune surveillance and regrow.
Another factor is the cumulative toxicity of treatment over time. Older patients often experience worsening kidney function and other organ damage due to both the disease and repeated therapies. This limits the ability to deliver subsequent lines of treatment at full intensity, reducing the chances of achieving long-lasting remission after relapse.
Additionally, multiple myeloma is a genetically heterogeneous disease, meaning that the cancer cells can evolve and develop resistance to therapies. This clonal evolution is accelerated by treatment pressure and is more problematic in older adults who may have had multiple prior therapies. Resistant clones survive and expand, leading to relapse that is harder to treat.
In summary, multiple myeloma relapse is frequent in older adults because their disease tends to be biologically more aggressive, their immune systems are less capable of controlling residual cancer, and their overall health limits the intensity and types of treatments they can receive. The combination of these factors results in a higher likelihood that myeloma cells persist after initial therapy and eventually cause the disease to return. Managing relapse in this population requires careful balancing of treatment efficacy and tolerability, often involving personalized approaches that consider the patient’s health status, disease characteristics, and prior therapies.
