Several chromosomal abnormalities have been associated with worse clinical outcomes for patients with newly diagnosed multiple myeloma (MM), but it is less well understood what the impact of these abnormalities are in the context of disease relapse. A recent study found that high-risk lesions, which the authors defined as t(4;14), t(14;16), and del(17p), appear to partially negate the benefit of autologous stem cell transplant (ASCT) compared with cyclophosphamide in patients with relapsed MM.1 The authors also evaluated the effect of other cytogenetic characteristics, such as t(11;14), MYC rearrangements, del(17p), 13q deletion [del(13q)], and hyperdiploidy.
The study is an update of the Myeloma X Trial, which included 174 patients across 51 hospitals in the United Kingdom who had relapsed multiple myeloma at least 12 months after upfront ASCT. It randomly assigned the patients, following reinduction therapy, to receive either high-dose melphalan plus salvage ASCT or weekly high-dose cyclophosphamide.
The current study confirms 2 earlier reports from the Myeloma X trial that found that salvage ASCT led to better clinical outcomes than cyclophosphamide in the relapse setting.2,3 With a median follow-up time of 76 months, the overall survival (OS) for the ASCT group was 67 months, compared with 55 months for the cyclophosphamide group.
“But the reason for publishing this paper is the cytogenetics,” TCM “Curly” Morris, MD, a retired professor of hematology at Queen’s University in Belfast, Northern Ireland, and one of the Myeloma X Trial investigators, told Cancer Therapy Advisor. The study focused on the presence of several high-risk genetic lesions found through fluorescence in situ hybridization (FISH) analysis. The ongoing Myeloma XII Trial will also take into account chromosome 1 alterations, which are now known to be high-risk lesions as well, said Dr Morris.
The most detrimental lesions present at time of first relapse were t(4;14) translocations and MYC rearrangements. The overall OS hazard ratio for patients in the ASCT group, as well as those who switched from cyclophosphamide to ASCT, compared with those who did not receive ASCT, was 0.46 (95% CI, 0.25-0.85). In contrast, the OS hazard ratio for the subset of patients with a t(4;14) lesion was 2.56 (95% CI, 0.23-29.12), and 1.76 for those with MYC rearrangements (95% CI, 0.23-13.26). On the other hand, the OS hazard ratio for individuals with hyperdiploidy was 0.15 (95% CI, 0.00-5.13). There were not enough individuals in the study to determine the impact of combinations of genetic lesions on OS, Dr Morris said.