Autologous transplantation in elderly patients with multiple myeloma: are we asking the right questions?

Multiple myeloma is a disease of the elderly. Survival outcomes remain unacceptably low in older adults with multiple myeloma. To date, no obvious difference in tumor biology has been elucidated to explain the survival disparity between older and younger patients. Multiple factors including comorbidity, performance status, decreased physiologic reserve and potentially undertreatment contribute to poor outcomes in elderly patients with multiple myeloma. High-dose chemotherapy with autologous stem cell transplantation (ASCT) is increasingly being used to treat elderly patients with multiple myeloma in an effort to improve survival outcomes. Recent case comparison studies, and preliminary transplant registry data suggest that selected older patients can be treated with high-dose chemotherapy effectively with similar toxicity and survival benefits compared to younger patients. Traditional upper age limits for autologous transplantation are being challenged along with the definition of ‘elderly’ itself. Ultimately, the role of high-dose chemotherapy with stem cell rescue in the upfront treatment of older adults with multiple myeloma can only be established by prospective randomized trials. In the process of designing studies to investigate the use of ASCT in older patients, multiple issues unique to the elderly population will need to be considered. First, it will be critical to develop and validate patient selection algorithms that incorporate measures of comorbidity, cognitive function, physiologic reserve and psychosocial function to identify patients most likely to tolerate and benefit from ASCT. Second, preparative and conditioning regimens will need to be further tailored to maximize the benefit to risk ratio. Finally, outcome measures in clinical trials should include disability and quality of life measures, which may be equally important in making treatment decisions for older patients. The future application and study of autologous transplantation in older patients with multiple myeloma provides a unique opportunity to challenge ageism and serve as a model for development of tailored assessments and interventions in this population.