Equivocal Significance of Prior Malignancies to Predict Overall Survival of Multiple Myeloma Patients after Autologous Hematopoietic Cell Transplant

Abstract

Introduction Hematopoietic cell transplantation (HCT)-specific comorbidity index (Sorror et al. Blood 2005) is highly recommended by National Marrow Donor Program as a risk assessment tool before HCT. Prior malignancies has one of the highest weighted score of 3 in this risk model. The isolated prognostic value of prior malignancies has not been evaluated in Multiple Myeloma (MM) patients (pts) who underwent autologous HCT (AHCT) in large databases. We hereby used national cancer database (NCDB) to evaluate this. Methods NCDB covers more than 70% of newly diagnosed cancer pts in the U.S. We reviewed NCDB, using ICD-O code of 9732, to identify pts who were diagnosed with MM between 2010 and 2014, underwent systemic treatment within 90 days of the diagnosis, and subsequently AHCT. Prior malignancy was not incorporated into Charlson comorbidity index at NCDB and reported separately. Average annual volume of a cancer center for MM is calculated among pts who met the inclusion criteria. Overall survival (OS) was estimated by the Kaplan-Meier method and compared with the log-rank test. Cox hazard analysis was performed to identify independent predictors of OS. Results We reviewed 12,427 pts and included 4358 pts who met inclusion criteria. Of which, 2481 (57%) were male, 693 (16%) were black, and 412 (10%) had at least one malignancies prior to MM. Median age at the diagnosis and time to initiation of systemic treatment after the diagnosis were 60 years (range: 25 – 80) and 17 days (range: 1 – 90), respectively. The Charlson comorbidity index was 0, 1, and ≥2 for 3646 (84%), 558 (13%), 154 (3%) pts, respectively. Durie-Salmon stage (DSS) at diagnosis was 1, 2, and 3 for 562 (13%), 1040 (24%), 2756 (63%) pts, respectively. Patient and treatment characteristics are compared between prior and no prior malignancy cohorts in table 1. Median follow-up time of pts was 36 months. Five-year OS of MM pts with and without prior malignancies was 75.6% (95% CI: 69.6 – 82.2) and 73.9% (95% CI: 71.6 – 76.2), respectively (p = 0.7) (Figure 1A). On multivariable analysis, each 10-year increase in age (HR 1.14, 95% CI: 1.02 – 1.26, p = 0.017), each 1 increase in comorbidity index (HR 1.24, 95% CI: 1.08 – 1.42, p=0.002) and year of MM diagnosis (HR 1.15, 95% CI: 1.06 – 1.24, p = 0.0008), DSS 3 vs 1 or 2 (HR 1.38, 95% CI: 1.16 – 1.64, p=0.0002), immunotherapy prior to AHCT (HR 0.72, 95% CI: 0.61 – 0.86, p = 0.0001), and each 10 increase in annual AHCT volume of a cancer center for MM (HR 0.98, 95% CI: 0.97 – 0.99, p = 0.016) were independent predictors of OS (Table 2). Conclusion In this large cohort analysis, prior malignancy was not a predictor of OS for MM pts who underwent AHCT. The role of prior malignancies in defining transplant eligibility requires future evaluation and the weighted value of this item in the comorbidity index should be considered for downward revision.