Improving Risk Stratification in Standard-Risk Myeloma Patients: Age, Bone Marrow Involvement Independently Predict Survival

Though the field of multiple myeloma (MM) has seen many advances in treatment in the past two years – including three new drug approvals – patients who have so-called standard-risk cytogenetics often have poor survival outcomes. These poor outcomes indicate that there is still a need for better risk-stratification methods, according to Moritz Binder, MD, MPH, of the Department of Internal Medicine at the Mayo Clinic in Rochester, Minnesota, who presented results of a new risk prediction model using fluorescence in situ hybridization (FISH) at the 2016 ASH Meeting on Hematologic Malignancies.

With this study, Dr. Binder and colleagues sought to identify demographic, clinical, and cytogenetic characteristics that would predispose MM patients with standard-risk cytogenetics to poor three-year overall survival (OS).

The study included 449 patients diagnosed with MM between July 2004 and July 2014 at the Mayo Clinic. Patients were included if they underwent FISH evaluation within six months of diagnosis and received treatment with an immunomodulator, proteasome inhibitor, or a combination of both.

Patients were excluded from the study if they:

  • had high-risk cytogenetics, which was defined as del(17p), t(14;16), and t(14;20)
  • had intermediate-risk cytogenetics, which was defined as t(4;14) and gain(1q)
  • were lost to follow-up within three years

Bone marrow aspirates were evaluated for deletions, monosomies, trisomies, and tetrasomies using chromosome- or centromere-specific FISH probes.

The median patient age was 65 years (range = 31-95 years), and 60 percent were male (n=270). Median OS was longest in the group of patients who survived at least three years (n=332; 74%), compared with the entire patient cohort (n=449) and those who did not achieve three-year OS (n=117; 26%):

  • 8.0 years for the entire patient cohort (range = 6.4-8.6 years)
  • 10.5 years for those who survived at least 3 years (range = 8.3 years – not reached)
  • 1.4 years for those who did not survive at least 3 years (range = 1.1-1.6 years)

Other risk factors independently associated with lower rates of three-year OS included disease stage, older age, greater extent of bone marrow involvement, karyotype, and lower platelet count at the time of diagnosis (TABLE).

“The model had excellent discrimination,” Dr. Binder and colleagues noted, “and correctly classified 83 percent of the patients, with 56 percent sensitivity and 92 percent specificity.” This translated to a positive predictive value of 71 percent, and a negative predictive value of 86 percent.

“One-fourth of the patients are experiencing less than three years of overall survival after diagnosis,” Dr. Binder and colleagues concluded. “These findings emphasize the importance of further risk stratification and the need for reliable predictors of poor clinical outcomes in this patient population.”


Reference

Binder M, Rajkumar SV, Ketterling RP, et al. Predicting poor overall survival in patients with newly diagnosed multiple myeloma and standard-risk cytogenetics treated with novel agents. Abstract #89267. Presented at the ASH Meeting on Hematologic Malignancies, September 16-17, 2016; Chicago, IL.

TABLE. Factors Associated With Poor Overall Survival at Three Years
Parameter Value Odds Ratio p Value
ISS stage I, II, III 1.85(95% CI 1.29-2.66) 0.001
Age <65 years, 65-75 years, >75 years 1.81(95% CI 1.28-2.56) 0.001
Plasma cells <20% in bone marrow 2.64(95% CI 1.26-5.54) 0.010
Karyotype Normal, hyperdiploid, other 2.8(95% CI 2.09-3.74) <0.001
Thrombocytopenia <150×109/L 2.74(95% CI 1.47-5.09) 0.001
ISS = International Staging System

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