Excess Mortality Risk Shows Myeloma Is Still ‘Incurable’

Three year OS was significantly worse compared with the general population, with a persistent risk for relapse.

Young patients with multiple myeloma had a 20-fold excess mortality risk at 3 years compared with the general population, suggesting that myeloma remains an incurable cancer.

“We found that survival outcomes for young patients with multiple myeloma are strikingly different from those seen with similarly aged patients with Hodgkin lymphoma [HL] and diffuse large B-cell lymphoma [DLBCL],” wrote Praful Ravi, of Mayo Clinic, Rochester, Minnesota, and colleagues, in Blood Cancer Journal. “Young patients who survive 3 years with DLBCL and HL achieve true cure with an overall survival similar to the background population. In contrast, patients with multiple myeloma and follicular lymphoma [FL] continue to relapse over time, with a significantly inferior overall survival to the background population.”

According to the study, use of the terms “functional” or “operational cure” has gained use among investigators to denote patients with myeloma who remain in complete response for a prolonged period. However, many patients with myeloma have a persistent risk for relapse.

In this study, Ravi and colleagues looked at survival and tested the idea of “cure” in patients with myeloma 50 years of age or younger, comparing these outcomes with those of similar patients with three other hematologic malignancies: FL, DLBCL, and HL. All patients were diagnosed between 2005 and 2015.

“Put simply, cure should be viewed as successful delivery of treatment(s) for a defined period of time with subsequent complete resolution of the disease,” the researchers wrote. “The patient should then expect to be able to enjoy a quantity and quality of life comparable with healthy counterparts once treatment has been completed.”

The researchers defined survival using standardized mortality ratios (SMRs). They found that compared with a background US population, all four cancers were associated with excess mortality risk (myeloma SMR = 19.5; FL SMR = 4.2; DLBCL SMR = 13.0; and HL SMR = 5.2).

The researchers suggested that cure was most likely to occur within the first 3 years after diagnosis and be reflected by overall survival similar to the background population. With a 36-month landmark, patients with either myeloma (SMR = 20) or FL (SMR = 3.8) had excess mortality risk compared with the general population. Patients with DLBCL (SMR = 3.1) or HL (SMR = 0.9) did not.

“We show that almost all patients with HL and DLBCL alive 3 years after diagnosis are essentially cured-their subsequent survival is similar to the matched background population and there is an unequivocal plateau in the OS [overall survival] and PFS [progression-free survival] curves,” the researchers wrote. “In contrast, in multiple myeloma, the 3-year landmark OS is markedly worse compared to the general population, and even among patients who live many years, there is a relentless risk of relapse. Hence, although young patients with multiple myeloma have a 10-year OS of nearly 50%, they are typically not being cured.”