How to treat frail patients with multiple myeloma?

During EHA 2024, an entire session was dedicated to the management of difficult to treat multiple myeloma (MM) populations. In this session, Dr Claudia Stege, haematologist at the Erasmus Medical Center in Rotterdam (The Netherlands), specifically addressed the treatment of elderly, frail MM patients.

Over the last decade, the introduction of many new treatment modalities dramatically improved the outcome for patients with MM. However, a higher age and a poor performance status continue to be associated with a worse outome. In this respect, a complete geriatric assessment of elderly MM patients can help to determine the prognosis of patients. Over the years, several frailty scores have been developed for MM patients, of which the IMWG frailty score and the simplified frailty score are the ones that are used most frequently.^1,2

Unfortunately, elderly, and frail patients are usually excluded from clinical studies, resulting in a data gap on the performance of the currently available treatment regimens for MM patients in patients with a poorer performance status. Based on the results of the phase III MAIA study, the combination of daratumumab-lenalidomide and dexamethasone (DRd) has become the standard of care first line treatment of transplant-ineligible MM patients. Interestingly, this study demonstrated that DRd significantly outperformed Rd irrespective of the frailty status of patients.³ Nevertheless, also with this regimen, frail patients continue to have a worse prognosis than their fitter counterparts. The main reason for this can be found in a higher rate of early treatment discontinuation due to tolerability issues.

To generate more data on the efficacy and safety of novel MM treatment regimens, there is a need to include frail patients in future randomized controlled trials and to generate prospective real-world data with these regimens in elderly and/or frail patients.  In addition, treatment strategies should be evaluated in which the treatment intensity is adapted to the frailty of the individual patient.