NEW ORLEANS—An ongoing risk assessment of multiple myeloma patients' “conditional survival” constitutes an attractive tool to predict outcome, supplement existing measures, and help guide survivors in planning their future. That was the conclusion of a study presented here at the American Society of Hematology Annual Meeting (Abstract 1745).
Inclusion of additional variables and cytogenetics can define long-term versus short-term survivors in a multiple myeloma specific risk model, and should help to provide clinically relevant prognostic information, such as accurate estimates of cause-specific survival, to implement preventive and interventional strategies, said Martina Kleber, MD, a specialist in the Department of Hematology and Oncology at the University of Freiburg Medical Center in Germany.
‘Easily Accessible Parameters’
“These easily accessible parameters show clinicians which patients will have long-term or short-term survival and, importantly, define treatment strategies and guide planning their future. These are parameters oncologists use in their daily practice, and are especially important to characterize the patients into ISS [International Staging System] risk groups.”
Survival estimates are typically presented as the probability of surviving a given length of time after the diagnosis, or as overall survival, she explained. “But this does not reflect how prognosis changes over time. In contrast, conditional survival describes the probabilities of surviving a certain number of additional years given that patients have already survived a certain number of years.”
The concept of conditional survival provides additional information about how the risk of death may change over time, taking into account how long someone has already survived, she said. “In multiple myeloma, many prognostic parameters have been proposed to predict survival, but results on conditional survival are lacking,” Kleber said.
She and her colleagues evaluated 816 consecutive patients treated between 1997 and 2011 with almost complete long-term follow-up. Initially, the researchers assessed age, gender, disease stage using the Durie & Salmon classification system, time of death, and last follow-up.
“We determined five-year conditional survival as the probability of surviving at least five more years as a function of years a patient had already survived since initial diagnosis,” Kleber said. Five-year conditional survival was stratified according to gender, stage, age, and other risk variables.
The overall survival probabilities were 50 percent at five years and 25 percent at 10 years. “The five-year-conditional survival remained constant over the years. As expected, the Durie & Salmon stage I versus stage II+III showed different five-year conditional survival estimates of 75 vs. 42 percent, respectively, for those who survived one year after diagnosis,” Kleber said.
Similarly, subgroups of patients younger than 60, 60 to 70, and older than 70 showed notably different five-year conditional survival estimates, but also remained constant over the course of time, with about 63, 51, and 27 percent, respectively, she reported.
“These patients are clinically stable. If a multiple myeloma patient survives four years, the life expectancy is another four years.”
Conditional survival for these multiple myeloma patients is nearly 15 percent over the years, which “indicates that multiple myeloma is a chronic disease,” Kleber continued. “Age is certainly a factor. Younger—under age 60 —patients have 60 percent conditional survival at five years, versus 20 percent for those over age 70.
To distinctively identify long-term survivors via conditional survival, the researchers performed a comprehensive analysis of various prognostic factors. The following were found to be significant additional risk factors: Karnofsky Performance Status (KPS) of less than 80 percent, two or more osteolyses, hemoglobin of less than 10g/dl, beta 2-microglobulin of at least 5.5 mg/l, and lactate dehydrogenase of at least 200 U/L.
In conclusion, Kleber said “Five-year conditional survival remained stable over time in the entire multiple myeloma cohort, indicating that this is an indolent disease. Age and advanced Durie & Salmon stage affected conditional survival, but gender did not.
“Univariate and multivariate risks allow us to reliably define long-term and short-term survivors and include variables that are easily assessable. The factors found via multivariate analysis for shorter overall survival are age over 62, KPS of less than 80 percent, two or more osteolyses, hemoglobin of less than 10 g/dL, and LDH of at least 200 U/L. These factors, combined with unfavorable cytogenetics, showed substantially different risk groups, which allowed us to much better stratify patients via ISS.”
She noted that overall survival stratified by ISS risk groups is not the same as conditional survival identified using risk factors. “Patients classified as ISS1 do not have the same overall survival as patients with conditional survival with zero or one risk factor. One-quarter of those with zero to three risk factors on conditional survival are alive 25 years later,” Kleber said.
Further analysis will compare this risk-stratification model with other novel risk scores. “This ongoing risk assessment should be important to define treatment strategies and guide cancer survivors in planning their future,” Kleber said. “Our next step is to look at how disease-related, host-related, and laboratory values contribute to long-term survival. These data will be available in a few months.”
Asked for his opinion for this article, Joseph Mikhael, MD, Consultant in Hematology/Oncology and Associate Professor of Medicine at the Mayo Clinic Scottsdale, said, “I support the concept of multiple myeloma as a chronic condition. We need to do more than classify patients based on progression-free survival or overall survival. I appreciate those two endpoints, but they don't always capture how patients do in the long-term.”
When considering multiple myeloma as a chronic disease, quality of life is more important than ever, he added. “We are trying to develop more quality-of-life tools for multiple myeloma patients. We don't have the ideal tool yet to measure quality of life. Even in clinical trials, we need to capture more information than survival, and also report quality-of-life issues.”