Myeloma at Younger Age Shortens Lifespan Despite Lengthy Overall Survival

Multiple myeloma at a younger age did not portend more aggressive disease or worse outcomes but significantly shortened lifespan as compared with the general population without myeloma, according to one of the largest studies of its kind.

Over a 15-year period, 214 patients with newly diagnosed myeloma at age 40 or younger had a 5-year overall survival (OS) of 84% and median OS of 14.5 years. That compared with a median OS of 8 to 9 years in prior studies of myeloma in older people.

After adjustment for the increased life expectancy of younger people in the general population, the younger myeloma cohort had a 5-year relative OS of 83.5%. Nevertheless, the standardized mortality ratio (SMR) estimate was almost 70 times greater than expected for the general population of people 40 or younger, reported Bruno Royer, MD, of Hopital Saint-Louis in Paris, and coauthors, in Blood.

“In this large retrospective cohort of patients with multiple myeloma diagnosed at ≤40 years of age, we found that baseline and disease characteristics are very similar to those of older patients,” the authors said in their summary of the findings.

“These very young patients present a long OS, despite subsequent relapses shown by the short PFS [progression-free survival], but a high increase in mortality compared with the general population,” they wrote. “Common adverse predictors of OS in older patients are confirmed to worsen OS in this particular population. Notably, we confirmed that high-risk cytogenetics was a reliable predictor of poor OS.”

Development of minimal residual disease-adjusted clinical strategies may help “further extend the encouraging OS” of younger patients with myeloma, they added.

Though widely considered a disease of older age, myeloma can occur in younger people, a key point of the study, noted the authors of an accompanying editorial.

“These patients have significantly different life challenges compared with older patients,” wrote Ola Landgren, MD, and Dickran Kazandjian, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami.

“Based on experience from our own clinics, for example, younger patients with myeloma face different hurdles such as childcare, pregnancy, career challenges, and other life circumstances that cause additional stress,” they continued. “There is need for more research focusing on younger patients with multiple myeloma and their needs, including clinical management, exploration of differences in disease biology, social support, drug development, and long-term follow-up of therapies.”

The median age of patients with myeloma approaches 70, and fewer than 2% of patients are younger than 40 at diagnosis. Limited data, primarily from small cohorts, have provided few insights into disease characteristics, prognostic factors, and outcomes in younger patients with myeloma. Despite improved treatment for myeloma, no standard of care exists for younger patients and the role of stem-cell transplant remains controversial, Royer and coauthors noted.

To address the lack of information, investigators in the French Myeloma Intergroup retrospectively reviewed medical records for patients 40 and younger with newly diagnosed multiple myeloma from January 2000 through December 2015. They identified 214 patients who had a median age of 37 at diagnosis.

The cohort comprised 189 patients with symptomatic myeloma, nine with primary plasma cell leukemia, 10 with smoldering myeloma, four with solitary plasmacytoma, and two with Randall disease. Overall, the younger patients had disease characteristics similar to those observed in older patients with myeloma, anemia in 35%, renal impairment in 17%, and hypercalcemia in 13%. High-risk cytogenetics was identified in 34 of 189 (18%) patients.

However, almost half of the patients had an International Staging System (ISS) score of 1, a substantially greater proportion than observed in older patients with myeloma. That factor could have contributed to the long OS, the authors acknowledged.

With respect to treatment, more than 90% of the patients received standard-of-care induction therapy, and 93% underwent autologous stem-cell transplantation. Almost 60% of the patients received consolidation or maintenance therapy, 80% had received a proteasome inhibitor or an immunomodulator at some time during treatment, and a fourth of the patients received allogeneic stem-cell transplants. Among 191 evaluable patients, 38% achieved complete response to first-line therapy, a third had very good partial response, 24% had partial response, 2% had stable disease, and 2% had progressive disease.

The cohort had a median follow-up of 76 months. The data also showed a median PFS of 41 months. The estimated SMR of 69.9 confirms “that multiple myeloma dramatically shortens the survival of young patients despite an extended survival after diagnosis,” the authors noted.

A multivariate analysis identified bone lesions (HR 3.95, P=0.01), high ISS score (HR 2.14, P=0.03), and high-risk cytogenetics (HR 4.54, P<0.0001) as significant predictors of poor outcomes. Among predefined covariables, shorter time to onset of progression significantly reduced OS (HR 13.2, P<0.0001).