New prognostic tools for myeloma

In this issue of Blood, Palumbo et al show, in a study performed with the cooperation of the International Myeloma Working Group (IMWG), that detailed systematic geriatric assessment of elderly myeloma patients might be a useful tool for identifying fit and frail individuals.¹  Like most malignancies, multiple myeloma mainly affects elderly patients. Even so, in daily clinical practice, we usually only consider chronological age (ie, is the patient under or above 65 years of age?). However, it is quite obvious that there is a huge difference between a 70-year-old fit patient and a frail patient above the age of 80.

Using data from almost 900 patients participating in 3 different clinical trials, IMWG has managed to identify a group of patients with highly significant but worse progression-free and overall survival. This inferior survival is most probably due to a larger frequency of treatment discontinuations and nonhematologic adverse events. The group of frail patients was defined by using geriatric assessment tools considering comorbidities and cognitive and physical status and by adding extra age intervals (65 to 74, 75 to 79, and ≥ 80), and the evaluation was performed at diagnosis, which avoided interference with treatment-related events.

It is well known that myeloma is a disease in which prognosis varies widely.²  There have been several systems to classify myeloma, from the study by Durie and Salmon³  to the International Staging System (ISS).⁴  They have all had their benefits, but so far they have not been able to provide information for adjusting the treatment of the individual patient. In this former study, the authors show that their new system could produce information not possible to obtain by using standard performance status, ISS, or even biological data from chromosomal analyses, which we normally regard as very important prognostic tools.

The present study is also important, apart from giving prognostic information, as the assessment system has the potential to give guidance for individual treatment regimens. By identifying frail patients, it could help the clinician choose well-tolerated, low-toxicity combinations, and thereby avoid harmful treatment regimens. Another potential important issue for a new robust frailty scoring system could be that elderly patients found fit could benefit from more intense treatment. In a study using population-based data, it was shown that regions in Sweden using more intense regimens for elderly patients with acute myeloid leukemia (AML) showed better survival results⁵  and these findings led to a change in treatment routines for elderly AML patients.

A limitation with this study is that data are based on patients participating in clinical trials, where the frailest patients are excluded. Therefore, it would be valuable if this system could be supported by so-called “real world” data from large population-based registries.

However, currently, these evaluations would be useful if they were included in upcoming clinical trials, making future comparisons between studies more adequate. Indeed, in a meta-analysis of one of the approved first-line therapies in Europe (melphalan, prednisone, and thalidomide), the results from the 6 trials differed widely, and it has been speculated that the different performance status of participating patients, even though apart from 1 study they were all >65 years of age, was the main cause.⁶  Also, as mentioned in this IMWG study, there are studies showing no difference between doublet and triplet treatment regimens, which accordingly might be due to less tolerability for the more intensive combinations among the frail patients.^7,8 

In conclusion, this report from the IMWG provides an evaluation system that enables the clinician to make a more detailed treatment decision. In the future, with a rapidly growing aging population, it will become increasingly important to tailor the treatment to the individual patient, thus avoiding harm and gaining maximal efficacy.