Analysis Identifies Potential Biomarker of Frailty in Multiple Myeloma

Neutrophil to lymphocyte ratio may indicate the presence of frailty among older adults with multiple myeloma.

Neutrophil to lymphocyte ratio (NLR) could serve as a readily available potential biomarker of frailty among older adults with multiple myeloma (MM), according to research published in the Journal of Geriatric Oncology.

Specifically, NLR combines “a marker of inflammation (neutrophilia) and reduced cell turnover (lymphopenia) to reflect aging-related alterations in the immune system.”

Median patient age at MM diagnosis is 70 years, and in the next 15 years, it is expected that approximately 75% of new cases will be in patients over 65 years in age. However, despite improving treatment options, outcomes are still suboptimal for this patient population as older adults continue to have high early mortality, excess treatment-related toxicity, and inferior survival, authors explained.

Frailty, defined as an “age-associated decline in reserve and function resulting in a reduced ability to cope with acute or external stressors faced every day,” is associated with poor outcomes among adults with MM. Although several methodologies of assessing frailty exist, restraints on time and resources have inhibited widespread adoption in routine clinical practice, researchers noted.

Previous research has indicated that NLR can predict survival and serve as a frailty marker among older individuals with and without cancer; however, its role in patients with MM remains unclear.

To better understand the potential use of NLR in MM, investigators assessed the association between pretreatment NLR, frailty, and overall survival using data gleaned from the Flatiron Health electronic health record (EHR)–derived database.

All patients included in the analysis had a diagnosis of MM between 2011 and 2020 and were at least 60 years old at the time of diagnosis. Individuals also had a record of a pretreatment absolute neutrophil and lymphocyte counts up to 90 days before the start of first-line therapy and were followed until death or last date of last structured activity in the EHR.

A total of 1729 individuals were included in the final analyses, with a mean (SD) age of 72 (6.7) years at MM diagnosis. Of these, a slim majority (52.8%) were male and 61% were non-Hispanic White. Researchers stratified calculated NLR values into quartiles (Q).

Authors found the following:

  • Median NLR was 2.13 (interquartile range, 1.44-3.31).
  • Of the 1135 patients with known frailty status, 55% met criteria for frailty.
  • Multivariable analysis revealed a 2.1-fold higher odds of frailty (95% CI, 1.42–3.10; P < .001) for patients in the NLR Q4 group vs the NLR Q1 group.
  • In a multivariable analysis, adjusting for age, sex, race/ethnicity, M-protein type, stage, high-risk cytogenetics, baseline creatinine, lactate dehydrogenase, and type of first-line therapy, patients in the NLR Q4 group had a 1.51 times increased hazard of death (95% CI, 1.15-1.98; P = .002) compared with those in the NLR Q1 group.
  • Compared with nonfrail patients, those categorized as frail had inferior overall survival (median, 7.2 years vs 3.7 years; log rank P < .001).

“Because absolute neutrophil and lymphocyte counts are routinely obtained as a part of initial workup for MM, NLR represents an easily obtained potential biomarker for frailty that can help identify older adults with MM who are at risk of inferior outcomes and provide an opportunity for targeted interventions to mitigate this impact,” the authors concluded.

Inflammation has been put forward as one potential change that could be linked with frailty in older individuals, as proinflammatory cytokines could promote protein degradation or affect metabolic pathways.

More research is warranted on the association between NLR and survival in patients with MM and on older adults with MM in general.

In the current analysis, frailty information could only be ascertained from those with complete data recorded in the EHR, marking a limitation. An underrepresentation of African Americans in this cohort also marks a limitation. “This is relevant because benign ethnic neutropenia is frequently seen among African Americans and the precise role of NLR in this population needs to be clarified,” researchers explained.


Giri S, Dahal S, Bal S, et al. Pre-treatment neutrophil to lymphocyte ratio as a biomarker and predictor of survival among older adults with multiple myeloma. J Geriatr Oncol. Published online December 17, 2021. doi:10.1016/j.jgo.2021.12.004