Sex Differences in Multiple Myeloma Biology but not Clinical Outcomes: Results from 3894 Patients in the Myeloma XI Trial

Abstract

Background: Sex differences in the incidence and outcomes of several cancers are well established. Multiple myeloma (MM) is a malignant plasma cell dyscrasia accounting for 2% of all new cancer cases in the UK. There is a clear sex disparity in MM incidence, with 57% of cases in males and 43% in females. The mechanisms behind this are not well understood and the impact of sex on patient outcomes has not been thoroughly explored.

Patients and methods: We investigated the association of sex with baseline disease characteristics and outcome in 3894 patients recruited to the phase III UK NCRI Myeloma XI trial, in which treatment exposure to lenalidomide predominated.

Results: Females were significantly more likely to have the molecular lesions t(14;16) and del(17p) and were more likely to meet the cytogenetic classification of high-risk (HiR) or ultra-high-risk disease (UHiR). There was no difference in progression-free survival (PFS) or overall survival (OS) between the sexes in the overall population.

Conclusion: Our data suggest that the genetic lesions involved in the initiation and progression of MM may be different between the sexes. Although females were more likely to have the poor prognosis lesions t(14;16) and del(17p), and were more likely to be assessed as having HiR or UHiR disease, this was not associated with reduced PFS or OS. In female patients the trial treatment may have been able to overcome some of the adverse effects of high-risk cytogenetic lesions. MicroAbstract Multiple myeloma (MM) is more common in males compared to females but the reasons behind this are not well understood and the impact of sex on patient outcomes is unclear. This study demonstrates fundamental differences in genetic lesions underlying the biology of MM between males and females. However, we found that progression-free survival and overall survival were the same in both sexes.

Keywords: Clinical trials; Immunomodulatory drugs+; Sex differences; myeloma.

Figure 1

Overall PFS (A) and OS (B) for males and females from induction randomization. PFS = progression-free survival; OS = overall survival.

Figure 2

Forest plot of PFS (A) and OS (B) hazard ratios by induction regime and maintenance regime. PFS = progression-free survival; OS = overall survival; CTD = cyclophosphamide, thalidomide, dexamethasone; CRD = lenalidomide, cyclophosphamide, dexamethasone; CTDa = cyclophosphamide, thalidomide, dexamethasone (attenuated); CRDa = lenalidomide, cyclophosphamide, dexamethasone (attenuated).

Figure 3

OS by risk status for males (A) and females (B). Comparison of OS for males and females with SR disease (C), HiR disease (D), and UHiR disease (E). OS = overall survival; SR = standard-risk disease; HiR = high-risk disease; UHiR = ultra-high-risk disease.