Trends in the risk of second primary malignancies among survivors of chronic lymphocytic leukemia

Abstract

With improving survivorship in chronic lymphocytic leukemia (CLL), the risk of second primary malignancies (SPMs) has not been systematically addressed. Differences in risk for SPMs among CLL survivors from the Surveillance, Epidemiology, and End Results (SEER) database (1973-2015) were compared to risk of individual malignancies expected in the general population. In ~270,000 person-year follow-up, 6487 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI:1.17-1.23). The higher risk was for both solid (SIR 1.15; 95% CI:1.12-1.18) and hematological malignancies (SIR 1.61; 95% CI:1.5-1.73). The highest risk for SPMs was noted between 2 and 5 months after CLL diagnosis (SIR 1.57; 95% CI:1.41-1.74) and for CLL patients between 50- and 79-years-old. There was a significant increase in SPMs in years 2003-2015 (SIR 1.36; 95% CI:1.3-1.42) as compared to 1973-1982 (SIR 1.19; 95% CI:1.12-1.26). The risk of SPMs was higher in CLL patients who had received prior chemotherapy (SIR 1.38 95% CI:1.31-1.44) as compared to those untreated/treatment status unknown (SIR 1.16, 95% CI:1.13-1.19, p < 0.001). In a multivariate analysis, the hazard of developing SPMs was higher among men, post-chemotherapy, recent years of diagnosis, advanced age, and non-Whites. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL.

Fig. 1

Second primary malignancy (SPM) diagnoses by site, with significantly increased (>1) or decreased (<1) incidence among patients with chronic lymphocytic leukemia (CLL) as the primary malignancy over time in the SEER database

Fig. 2

Observed/expected (O/E) incidence (standardized incidence ratio, SIR) of second primary malignancies (SPMs) by latency period after the diagnosis of chronic lymphocytic leukemia (CLL) over time

Fig. 3

Observed/expected (O/E) incidence and absolute excess rate (AER) for second primary malignancies (SPMs) by patient age at the time of chronic lymphocytic leukemia (CLL) diagnosis

Fig. 4

Hazard of developing second primary malignancies (SPMs) in patients with a diagnosis of chronic lymphocytic leukemia (CLL) in a multivariate model utilizing patient gender, age category at diagnosis, race, year of diagnosis, and whether or not the patients received chemotherapy

Fig. 5. Cumulative incidence of second primary malignancies (SPMs) over time.

Periods for a solid tumors and b all hematologic malignancies. Study periods include: (1) 1973–1982, (2) 1983–1992, (3) 1993–2002, and (4) 2003–2015