Abstract
The management of newly diagnosed transplant-ineligible multiple myeloma remains challenging, largely because frailty complicates treatment decisions and frequently leads to the exclusion of frail patients from pivotal clinical trials. Recent subgroup analyses provide useful insight into whether quadruplet therapy may offer advantages over triplet therapy in this population. Data from the IMROZ and CEPHEUS trials were reviewed to compare outcomes between quadruplet and triplet regimens in both the overall intent-to-treat cohorts and the frailty-defined subgroups. Frailty was assessed using the International Myeloma Working Group (IMWG) frailty index in CEPHEUS and the simplified IMWG frailty score in IMROZ. Across both trials, patients with impaired performance status receiving quadruplet therapy demonstrated longer progression-free survival and higher rates of minimal residual disease negativity compared with those receiving triplet therapy. These findings suggest that quadruplet regimens may provide meaningful clinical benefit even among selected frail patients when treatment decisions are guided by comprehensive frailty assessment and individualized clinical judgment. Additional real-world evidence is needed to confirm tolerability, optimize patient selection, and further clarify the role of quadruplet therapy in this vulnerable population.
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