Risk of Second Cancers Among Multiple Myeloma (MM) Patients in the Era of Novel Agents: Analysis Using the Surveillance, Epidemiology and End Results (SEER) Database

Recent data have drawn interest in the potential association of lenalidomide and the risk of developing of second cancers in patients with MM. However, available data are limited. Though there is lack of chemotherapy specification, SEER data segregated into diagnosis periods may be useful as a surrogate to detect changes in the incidence of second cancers corresponding to the introduction of novel agents.

Patients who had MM diagnosed as a first cancer from 1973–2008 were identified in the SEER 17 database. We included only patients who survived at least 2 years after diagnosis. Time segments were created based on the era of novel agents approved for MM: before January 2000 (Period 1; control), January 2000-April 2003 (Period 2; off-label thalidomide), May 2003-April 2006 (Period 3; bortezomib approval), May 2006-September 2006 (Period 4; thalidomide approval) and October 2006-December 2008 (Period 5; lenalidomide approval). The primary outcome measure was incidence of second cancer within 2 years of MM diagnosis. All second cancers were included except for myelodysplastic syndrome and in situ cancer that were not of breast and bladder. Odds ratios (ORs) were adjusted and P values < 0.05 were considered statistically significant.

There were 29,259 eligible patients. Majority were males (53%) and the mean age at MM diagnosis was 65 years (std.+/− 12). The incidence of second cancers was associated with period of diagnosis (P = 0.048), sex (P < 0.001), treatment (P < 0.001), and age (P < 0.001), but not with race (P = 0.108). Multivariate analyses showed that higher risk of second cancers was associated with older age (OR = 1.03; P < 0.001), male sex (OR = 1.41; P < 0.001), radiation and/or surgery as compared to neither treatment (radiation and surgery OR = 1.77, radiation only OR = 0.82, surgery only OR = 2.31; P values: 0.002, 0.040, and <0.001, respectively), and Periods 3 and 4 as compared to Period 1 (Periods 2–5 ORs: 1.11, 1.22, 1.63, and 1.53, respectively; P values: 0.260, 0.033, 0.011, and 0.096, respectively).

Our population-based study suggests that the risk of developing second cancers in patients with MM may be increased in the recent decade wherein novel agents were introduced. A more specific study linking SEER to Medicare database is recommended in order to further define the risk specific to novel agents.

No relevant conflicts of interest to declare.