Effect of autologous hematopoietic stem cell transplant on the development of second primary malignancies in multiple myeloma patients

Abstract

Autologous stem cell transplant (aHSCT) is associated with improved survival for multiple myeloma (MM) patients but may be associated with second primary malignancy (SPM) development. Using the California Cancer Registry linked to statewide hospitalization data, we determined the cumulative incidence (CMI) of SPMs more than 1 year after MM diagnosis, accounting for the competing risk of death. AHSCT recipients were matched 1:2 to non-aHSCT patients. Adjusted hazard ratios (aHR) were estimated using the Fine and Gray method. Among 16,331 patients, 933 (5.7%) developed a SPM more than 1 year after diagnosis. The 10-year CMI of developing any SPM was 6.6%, 5.7% for solid tumor SPM and 0.9% for hematologic malignancies. The 10-year CMI of developing any SPM was similar among aHSCT [9.1% (7.7-10.7%)] and non-aHSCT [7.5% (6.5-8.6%)] (P = 0.26) recipients and there was no difference in solid-tumor SPMs (P = 0.98). The 10-year CMI of hematologic SPMs was higher among aHSCT recipients [2.1% (1.4-2.9%) vs. 0.8% (0.5-1.2%); P = 0.005], corresponding to a 1.3% absolute increase and an aHR of 1.51 (1.01-2.27). Ten-year myeloma-specific and non-cancer mortality rates were 59% (58.2-60.0%) and 18.1% (17.4-18.8%), respectively. Although aHSCT was associated with a small increase in hematologic SPMs, mortality was driven by MM and non-cancer causes.

Fig. 1. Cumulative incidence of mortality and second primary malignancy (SPM) among 1-year survivors of first primary multiple myeloma in California, 1991–2013.

The cumulative incidence of second primary malignancy (SPM) development accounting for the competing risk of death from multiple myeloma (MM), non-cancer related mortality (NC) and other cancer mortality (OC).

Fig. 2. Five-year cumulative incidence of second primary malignancy by treatment era among 1-year survivors of first primary multiple myeloma in California, 1991–2013.

The cumulative incidence of developing second primary malignancies in patient cohorts diagnosed between 1991–1997, 1998–2002, 2003–2007, 2008–2013, accounting for the competing risk of death. The 5 year cumulative incidence of SPM development was higher in those diagnosed between 2008–2013 [5.0% (4.3–5.8%)] compared to earlier eras: 3.8% (3.2–4.4%), 3.9% (3.3–4.6%), 3.4% (2.9–4.0%) in 2003–2007, 1998–2002, and 1991–1997.

Fig. 3. Cumulative incidence of second primary malignancy development among multiple myeloma patients with or without autologous stem cell transplant.

Overall solid hematologic footnote: A overall second primary malignancy (SPM), B Solid tumor SPM, and C Hematologic SPM by autologous stem cell transplant (aHSCT) treatment among matched 1-year survivors with first primary multiple myeloma in California, 1991–2013. aHSCT patients were matched to two patients without aHSCT on age, year of diagnosis, race/ethnicity, nSES status comorbidities, and follow-up time. Person time was calculated from aHSCT date to SPM, death, or last known follow-up from the cancer registry.

Fig. 4. Adjusted effect of autologous stem cell transplant (aHSCT) treatment compared to no aHSCT treatment on the risk of second primary malignancy (SPM) among 1-year survivors with first primary multiple myeloma in California, 1991–2014.

aHSCT was included as a time dependent covariate. Adjusted for the competing risk of death and baseline multiple myeloma characteristics (gender, race/ethnicity, age at diagnosis, treatment era of diagnosis, initial course of treatment, neighborhood socioeconomic status, comorbidities, initial health insurance, marital status, and urban vs. rural location of residence).