Hira Mian, MD, MSc, FRCPC is an Associate Professor in the Department of Oncology at McMaster University.

In today’s episode, we had the pleasure of speaking with Hira Mian, MD, MSc, FRCPC, an associate professor in the Department of Oncology at McMaster University in Toronto, Canada, about the role of dynamic frailty assessment in the management of transplant-ineligible patients with newly diagnosed multiple myeloma. At the 2025 International Myeloma Society Annual Meeting, Dr Mian presented a dynamic frailty analysis from 2 phase 3 trials: MAIA (NCT02252172), which evaluated daratumumab (Darzalex) in combination with lenalidomide (Revlimid) and dexamethasone (Dara-Rd), and CEPHEUS (NCT03652064), which evaluated daratumumab plus bortezomib (Velcade), lenalidomide, and dexamethasone (Dara-VRd).

In our exclusive interview, Dr Mian discussed why frailty should be understood as a dynamic, evolving clinical state rather than a fixed baseline characteristic. She highlighted that frailty scores changed meaningfully over time for a substantial proportion of patients in both MAIA and CEPHEUS, emphasizing the need to regularly reassess patient resilience and vulnerability throughout treatment. Dr Mian also reviewed how the addition of daratumumab improved outcomes across all dynamic frailty subgroups—including patients classified as ultra-frail—and described key safety considerations when applying these findings to real-world practice. Finally, she underscored the importance of designing future trials that prospectively incorporate dynamic frailty to better guide treatment selection and supportive care strategies for older adults with myeloma.

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Podcasts

Hira Mian, MD, MSc, discusses why frailty should be understood as a dynamic, evolving clinical state rather than a fixed baseline characteristic for patients with multiple myeloma.

Dynamic Frailty Assessment Underscores Need for Ongoing Evaluation in Transplant-Ineligible Multiple Myeloma: With Hira Mian, MD, MSc, FRCPC

Hira Mian, MD, MSc, FRCPC is an Associate Professor in the Department of Oncology at McMaster University

“This emphasizes that you can’t use a one-time frailty measurement; you need to be more dynamic. When we started looking at specific outcomes in terms of efficacy, minimal residual disease negativity rates, and progression-free survival, it was great to see that both for CEPHEUS and MAIA, [the addition of] daratumumab ended up helping all the subgroups dynamically across the different time points.”

Hira Mian, MD, an associate professor of medicine at McMaster University, discussed findings from a dynamic frailty analysis conducted in transplant-ineligible patients with newly diagnosed multiple myeloma enrolled in the phase 3 MAIA (NCT02252172) and CEPHEUS (NCT03652064) trials. These studies evaluated daratumumab (Darzalex) combined with lenalidomide (Revlimid) and dexamethasone (D-Rd) or bortezomib (Velcade), lenalidomide, and dexamethasone (D-VRd), respectively.

Mian emphasized that the analysis underscored the dynamic nature of frailty. In CEPHEUS, frailty status changed in 34% of patients over 4 years of follow-up, whereas in MAIA, 26% of patients experienced changes in frailty classification during the same length of time. These findings indicate that frailty is not a fixed characteristic and highlight the limitations of relying on a single baseline assessment to guide treatment decisions. Instead, ongoing evaluation of frailty is necessary to better align treatment strategies with evolving patient status, Mian noted.

Regarding efficacy, the addition of daratumumab provided consistent benefits across frailty subgroups, including patients classified as frail or ultra-frail. Improvements in minimal residual disease negativity rates and progression-free survival were observed in both trials, suggesting that daratumumab-containing regimens maintain clinical activity across varying levels of frailty. Importantly, even in patients considered ultra-frail, D-Rd and D-VRd demonstrated efficacy, supporting their use in populations often viewed as challenging to treat.

Mian noted that safety analyses indicated that daratumumab-based regimens were generally well tolerated. No unexpected toxicities emerged, and treatment discontinuations due to adverse effects did not differ significantly across frailty groups. Further research is needed to determine whether dynamic frailty changes have an independent effect on safety outcomes, but current data suggest the regimens remain manageable regardless of frailty status.

Mian concluded that these results have 2 major implications for clinical practice and future research. First, frailty should be recognized as a dynamic construct that requires repeated evaluation throughout the course of therapy. Second, future phase 3 trials should incorporate prospective, longitudinal frailty assessments to more accurately capture patient trajectories and inform tailored treatment strategies.

Videos

Hira Mian, MD, discusses findings from a dynamic frailty analysis conducted in transplant-ineligible patients with newly diagnosed multiple myeloma.

Hira Mian, MD

Articles

Dynamic Frailty Assessment Underscores Need for Ongoing Evaluation in Transplant-Ineligible Multiple Myeloma: With Hira Mian, MD, MSc, FRCPC

Dr Mian on Findings From a Dynamic Frailty Analysis in Transplant-Ineligible, Newly Diagnosed Multiple Myeloma