Trends in Incidence and Survival of Multiple Myeloma with Second Primary Malignancy,

Recent advances in the treatment of multiple myeloma (MM) have lead to improved patient outcomes and significant improvement in MM survival. Reports from ongoing randomized clinical trials have suggested that there may be an association between the types of treatment received, particularly certain novel therapeutic agents, and a higher incidence of second primary malignancies (SPM) among MM patients. In this analysis, we explored current patterns and trends in incidence and survival of MM between 1973–2008 to better characterize MM patients with second primary malignancies.

We used data from the National Cancer Institute Surveillance Epidemiology and End Results Program (SEER) to examine the incidence and survival trends in MM by SPM status between 1973–2008. We included all cases with MM as the first primary malignancy and calculated the age-adjusted annual incidence rates (AIR per 100,000) stratified by those with single primary (SP) MM and those with MM as the first of multiple primaries (FMP). All cases that were not microscopically confirmed or those with an MM diagnosis coded only from autopsy- or death certificates were excluded from the analysis. We used joinpoint regression models to calculate the annual percent change (APC) and to determine the best fitting line or set of lines that describes the MM temporal trends. A Monte Carlo permutation method was used to test for significance. We used multivariate Cox proportional hazard models to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for MM by SPM status, and all analyses were further stratified by year of diagnosis, age, sex, and race/ethnicity.

A total of 61,411 cases of MM were recorded in all SEER registries between the years 1973 and 2008. The final analysis included 49,801 SP and 3090 FMP cases. Overall, the AIR of MM was 5.31 (95% CI 5.26–5.36). The AIR of SP MM was 4.33 (95% CI 4.28–4.38) and 0.28 (95% CI 0.27–0.29) for FMP MM. Compared to women, men were 1.41 times (95% CI 1.38–1.44) and 1.95 times as likely to develop SP MM and FMP MM, respectively. African-Americans had the highest rate of SP MM (AIR 9.09; 95% CI 8.85–9.34) and FMP MM (AIR 0.69; 95% CI 0.62–0.76). We observed no significant trend in AIR of SP MM between 1973–2008 (APC 0.03). The rate of FMP MM was relatively stable, however we observed a small but statistically significant increasing trend in incidence between 1973 and 1992 (APC 2.9), followed by a decreasing trend between 1992 and 2008 (APC −3.2). The rate ratio of FMP to SP MM has remained stable at approximately 6% from 1973–2008.

The overall hazard ratio of mortality was 0.59 (95% CI 0.56–0.61) with a median survival of 3.6 years in the FMP MM versus 1.7 years in the SP MM patients. There was a statistically significant improvement in the survival of SP MM patients over the past three decades (P for trend < 0.001), with the most prominent increase in the 2002–2008 period with a HR of 0.67 (95% CI 0.64–0.69) when compared to those diagnosed in the 1973–1981 period. In contrast, the survival of FMP MM patients remained constant (P for trend=0.39). Although SP MM patients show a significant increase in survival over time, FMP MM survival remained stable and significantly higher. We further stratified the survival analysis by age, sex, and race/ethnicity. In all stratified analyses, FMP MM patients had a significantly better outcome compared to SP MM patients.

Although there has been significant improvement in survival for patients with SP MM in recent years, our results provide an epidemiologic evidence suggestive of a subtype of MM with a better outcome, yet a higher risk of secondary primary malignancies. The incidence rate and outcome of this possible subtype has remained unchanged over the last three decades. These findings are replicated when stratified by gender, race, age, and year of diagnosis. Recent advancements of MM treatment have seemed to only increase the survival of SP MM patients, while the survival of FMP MM patients remained stable. Further studies are needed to explore the potential genetic heterogeneity between MM with and without second primary malignancies.

No relevant conflicts of interest to declare.