Median overall survival (OS) for patients with multiple myeloma has improved substantially in the past 10 years, thanks to the approval of a number of new drugs. For patients who can undergo transplants, survival exceeds 80% at 5 years. But although many patients can live 7 to 10 years after diagnosis, outcomes can be highly variable, according to S. Vincent Rajkumar, MD, Professor of Medicine at the Mayo Clinic in Rochester, MN.
Patient factors are largely responsible for this variation, he said. Host factors that shift patients into the poor prognosis category include a performance status of 3 or 4, renal failure, advanced age, stage III disease (high tumor burden), and high-risk tumor biology.
Although patients with hyperdiploidy t(11;14) and t(6;14) are considered to be at standard risk for disease progression, those with t(14;16), t(14;20), deletion 17p, and high-risk gene-expression profile signatures have a high risk. “Even with the best-available therapy, these patients have a median survival of only about 2.5 years,” Dr Rajkumar noted.
In the intermediate-risk range is the t(4;14) subset. Their risk is “intermediate,” he said, “not because survival falls between the standard-risk and high-risk patients, but because they can have better outcomes if they are treated in a particular manner.”
Risk-Adapted Treatment
“What we know about these subtypes is that standard-risk patients do very well regardless of the therapy, with a median survival of more than 7 to 10 years now,” Dr Rajkumar observed. “But intermediate-risk patients do well only if given bortezomib early in the disease, followed by transplant, followed by bortezomib-based consolidation, followed by maintenance therapy for 2 to 3 years. Many studies have shown that with this approach, survival in this group is similar to, if not the same as, standard-risk patients.”
“On the other hand, you can give high-risk patients all the therapies we have, and they still have a median survival of 2.5 years,” he noted. In this group, the achievement of a complete response (CR) is critical, Dr Rajkumar emphasized.
In a study from the Arkansas group using the total therapy tandem transplant regimen, the 18-month survival rate was only 13% among high-risk patients when a CR was not achieved, whereas it exceeded 80% among complete responders (Haessler J, et al. Clin Cancer Res. 2007;13:7073-7079). In low-risk patients, OS was 87% regardless of whether patients achieved a CR.
Treatment should be adapted to this underlying risk, Dr Rajkumar emphasized. “Often, which approach the patient receives will depend on which physician they see, but we should always put the patient in the center. We should look at host factors, stage, tumor burden, tumor biology, and patient tolerability and preference, and individualize therapy accordingly,” he stressed.