A look at frailty in elderly multiple myeloma patients

This study reviewed evidence on how to categorize older multiple myeloma patients.

Advances in treatment approaches have improved response rates and survival for multiple myeloma patients. These typically involve combining immunotherapies, such as lenalidomide (Revlimid), with proteasome inhibitors, such as bortezomib (Velcade), with or without additional chemotherapy. However, many older patients are less likely to tolerate new treatments, particularly those patients that are considered frail (of poor physical and mental health). About 35 to 40% of patients are older than 75 years at diagnosis, but not all elderly patients are necessarily frail.  It is important to understand the potential treatment outcomes for elderly patients who are frail.

The aim of this review was to clarify how to categorize older multiple myeloma patients. 

The International Myeloma Working Group (IMWG) calculated a frailty index that takes age, additional medical conditions, and activities of daily living into account. This index was able to predict whether or not a patient had to discontinue treatment due to side effects. Frail patients had a 1.8 times higher rate of stopping treatment compared to fit patients. 17% of patients aged less than 75 years were categorized as frail.

A recent study found that the IMWG frailty index could predict survival in newly diagnosed multiple myeloma patients. The 3-year overall survival rate (proportion who have not died from any cause since treatment) for fit patients was 91%. It was 77% for intermediate-fit patients and 47% for frail patients.

The Revised Myeloma Comorbidity Index (R-MCI) calculates kidney function, lung function, impairment of daily living, frailty, and age as independent risk factors. One study involving 801 patients categorized 30.8% as fit based on R-MCI with an average overall survival of 10.1 years. 55.7% of patients were intermediate-fit with an average survival of 4.4 years. 13.5% of patients were frail with an average survival of 1.2 years.

The IMWG frailty index and R-MCI are currently the most effective in predicting survival and disease progression compared to other health assessment tools. Clinical trials that investigate how the two tools apply in clinical practice are ongoing.

Studies are also ongoing as to how best to treat frail myeloma patients. In one study, a reduced dosage of bortezomib-based treatment followed by maintenance therapy was given to a group of elderly patients. The results showed similar overall survival compared to patients receiving the full dosage. The rate of side effects was low. Another study showed that reducing the dosage of the steroid drug dexamethasone (Dexasone) in combination with lenalidomide was as effective as the higher dosage. Treatment duration, exposure for more than 2 years, and discontinuation rates were similar in patients older and those younger than 75 years.

This study discussed the need to appropriately manage frail multiple myeloma patients. The authors suggested that full-dose treatment can be applied in fit patients, whereas reduced therapy is recommended in frail patients. Trials that investigate tools that can help personalize therapy in elderly patients are ongoing.