Consider Frailty, Not Only Age, When Choosing Myeloma Drugs

Susan Mayor

September 27, 2015

ROME ― Functional status, as well as chronologic age, is significantly associated with survival in multiple myeloma, according to "real-life" registry data from the Netherlands.

Multiple myeloma is typically a disease of elderly people, with a median age at onset of 70 years. There have been major developments in treatment options for multiple myeloma during the past 20 years that have significantly improved overall survival. But minimal survival gain has been seen in elderly patients older than 70 years.

The main factor currently used to decide on treatment in patients with multiple myeloma is chronologic age, but there is growing recognition that frailty, determined on the basis of measures such as World Health Organization (WHO) performance status and the presence of comorbidities at diagnosis, may provide more useful measures.

"Geriatric assessment should be used to determine frailty instead of chronological age alone to decide on treatment choice for elderly myeloma patients," said Silvia Verelst, academic researcher in the Department of Haematology at Erasmus University Medical Center, Rotterdam, the Netherlands. She presented a study analyzing Dutch myeloma registry data by age group as well as frailty here at International Myeloma Workshop (IMW) 2015.

"Data on treatment effectiveness based on daily practice are sparse but necessary to provide complementary information [to that provided by clinical trials]," she said.

Comparing the Impact of Age and Frailty on Survival

The study analyzed treatment and survival in all patients with multiple myeloma aged 66 years and older at diagnosis between January 2004 and December 2010 in the south and west of the Netherlands. All patients were ineligible for autologous stem cell transplantation. They were followed for a median period of 33 months.

Overall survival was analyzed for the whole group of 532 patients (median age, 76 years at diagnosis). The researchers then looked at survival in three age groups at the time of diagnosis: 66- 69 years (113 patients, 21%); 70-79 years (257 patients, 48%); and 80+ years (162 patients, 30%).

They also analyzed survival by WHO performance status at diagnosis and by the number of preexisting comorbidities.

Nearly half (244 patients, 46%) were assessed as being of WHO performance status 1 (restricted in strenuous activity but able to carry out light work) when they were diagnosed with myeloma; one quarter (133, 25%) were classified as WHO status 0 (able to carry out all normal activities without restriction).

One in four of the patients (132, 25%) had two preexisting comorbidities. A similar number (125, 23%) had one comorbidity, and 14% (76 patients) had none.

Looking at use of different treatments, more patients aged 66-69 years received an immunomodulatory drug in 2004-2006 than those aged 70-79 or 80 years and older (40% vs 26% vs 12%, respectively). The proportion increased in 2007-2009 but remained slightly lower in the oldest age group (63%, 77%, and 58%).

"Choice of treatment showed to be significantly related with chronological calendar age at diagnosis," said Verlest.

Analysis showed significant differences in overall survival between the three age subgroups (P < .001), with median survival ranging from 10 months for patients aged 80 years and older to 44 months for those aged 66-69 years. WHO performance status at time of diagnosis was also significantly related to overall survival (P < .001), but number of comorbidities was not.

"There were no significant differences in the distribution of WHO performance status at the time of diagnosis among the different age subgroups," Verelst pointed out.

"Not all elderly patients are equally old at the same chronological age," she concluded. "Therefore, geriatric assessment to determine frailty instead of age alone should be used to make decisions on treatment choice."

She recommended use of on online tool such as the Myeloma Frailty Score Calculator for assessing prognosis in elderly myeloma patients.

Paying More Attention to Assessing Frailty in Practice

Commenting on the study, Keith Stewart, MB, ChB, consultant in hematology-oncology at the Mayo Clinic, Scottsdale, Arizona, told Medscape Medical News: "What this is highlighting is that myeloma is a disease of the elderly, and we should be paying more attention to assessing the frailty of the patient using a formal frailty score, particularly when we start to use more complicated chemotherapy regimens and try to extrapolate results from younger patients."

"It's quite new in the myeloma field to think about using a frailty score, and this is being used mainly as a research tool at the moment. But it's probably a good idea if we all did it," he suggested, although he cautioned that this would add further complexity to a clinic visit.

"Generally speaking, most physicians just do the 'eyeball' test, and performance status is based on a couple of quick questions: how much a patient is out of bed in a day and how physically active they are," he explained. But he added that involving a geriatrician would probably be useful in improving assessment of frailty in myeloma patients.

The study is part of the PHAROS project, a population-based registry to collect and analyze data on treatment and outcomes in patients with hematologic cancers in the Netherlands. Silvia Verelst and Dr Stewart have disclosed no relevant financial relationships.

International Myeloma Workshop (IMW) 2015: Abstract BP-042. Presented September 25, 2015.

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