Front-line therapies for elderly patients with transplant-ineligible multiple myeloma and high-risk cytogenetics in the era of novel agents

In multiple myeloma, certain cytogenetic abnormalities, such as t(4;14), t(14;16), and del(17p), are considered high risk and are associated with worse prognosis. Patients with these high-risk cytogenetic abnormalities, as well as those who are elderly and transplant ineligible, have not experienced the same degree of improved survival outcomes that other patients have seen with recent advances in the treatment of multiple myeloma. To date, no treatment regimen has demonstrated sustained and consistent survival benefits in elderly, transplant-ineligible patients with high-risk cytogenetic abnormalities and newly diagnosed multiple myeloma. Thus, there is an unmet need to identify effective treatment options for these patients and achieve outcomes parity with standard-risk patients. In this review, we assessed clinical trials of both doublet and triplet regimens for newly diagnosed multiple myeloma that included elderly, transplant-ineligible patients with high-risk cytogenetic abnormalities and that provided outcomes data stratified by cytogenetic risk status. We concluded that regimens containing an IMiD agent as the foundation of therapy, combined with agents that have synergistic mechanisms of action—including novel therapies—may in future investigations help overcome the poor prognosis of high-risk cytogenetic abnormalities in this vulnerable patient population.