PS1386 CARFILZOMIB AS PART OF A DOSE DENSE, LESS DOSE INTENSE TOTAL THERAPY APPROACH FOR HIGH RISK MYELOMA
Authors: F. Van Rhee, H. Wang, S. Thanendrarajan, C. Schinke, F. Davies, A. Erra, J. Sawyer, A. Rosenthal, D. Steward, P. Farmer, T. Prichett, C. Bailey, J. Epstein, B. Walker, A. Hoering, G. Morgan, B. Barlogie, M. Zangari
Journal: HemaSphere (2019)

Background: Jonsdottir et al. (Blood Adv. 2017) recently suggested that, among the population of Sweden, a prior malignancy diagnosis (PMD) before the onset of MM increases the risk for developing a subsequent primary malignancy (SPM) after multiple myeloma (MM). Their analysis, however, did not account for death before the onset of a SPM as a competing risk. Therefore, their risk estimates might overestimate the magnitude of SPM development. Aims: To complement and extend on their observations, we revisited their analysis on the impact of a PMD on the first onset of a SPM in MM by employing competing risk regression. Methods: We identified all MM patients diagnosed between 1994–2012 from the nationwide population-based Netherlands Cancer Registry (NCR). PMDs and SPMs-excluding basal cell carcinomas-relative to MM were identified from the NCR. Synchronous malignancies diagnosed ≤6 months prior to or after MM diagnosis, and malignancies diagnosed from autopsies were excluded. SPMs were classified into subtypes according to the 3rd edition of the International Classification of Diseases for Oncology. We used competing risk regression as per Fine and Gray 3/4 with death before the onset of a SPM as a competing risk 3/4 to estimate sub-distribution hazard ratios (SHRs) with 95% confidence intervals (CIs) for the association between a PMD in MM patients and the development of a first SPM overall. These associations were also calculated for the subtypes as per SPM. We used Cox regression to calculate hazard ratios (HRs) with 95% CIs for the association between a PMD and the risk of mortality. All analyses were adjusted for baseline MM characteristics (i.e. sex, age, and period of diagnosis). All patients were followed from date of MM diagnosis to date of first SPM, death or end of follow-up (February 1, 2017), whichever came first. A P < 0.05 indicated statistical significance. Results: Our analytic cohort included 16,710 MM patients, of whom 1,760 (10.5%) had at least one PMD. Patients with a PMD were older at MM diagnosis, as compared to those without (median age 76 vs. 70; P < 0.001). At a median time of 3.8 years from MM diagnosis to first SPM (range 0.5–19.4), 138 of 1,760 (7.8%) MM patients with a PMD developed a SPM, as compared to 1,079 of 14,950 (7.2%) MM patients without (P = 0.341). Overall, there was no evidence for an increased rate of a first SPM in MM patients with a history of PMD, as compared to those without a history of PMD (adjusted SHR, 1.15; 95% CI, 0.96–1.38; P = 0.131; Table). However, subgroup analyses showed that there was an increased rate of breast cancer as first SPM in patients with a history of PMD (adjusted SHR, 2.45; 95% CI, 1.04–5.78; P = 0.040; Table) and melanoma of the skin (adjusted SHR, 3.05; 95% CI, 1.26–7.37; P = 0.014; Table). Finally, there was no statistically significant association of a PMD with the risk of mortality (adjusted HR, 1.04; 95% CI, 0.98–1.10; P = 0.177).Summary/Conclusion: In this population-based study, there was no apparent overall association between a history of a PMD and the development of a SPM among MM patients. However, subtype analyses showed increased rates for breast cancer and melanoma of the skin. Our results are not entirely in line with those of Jonsdottir et al. Of note, since we accounted for death before the onset of a SPM as a competing risk, our estimates are unlikely to be plagued by overestimation. Moreover, our results may guide cancer surveillance for early detection and appropriate management of SPMs, as MM survivorship is expected to increase due to continues therapeutic advances.