Whereas detecting high-risk lesions at diagnosis can guide treatment decisions, the current study does not suggest that any of the chromosomal abnormalities at relapse would be grounds for choosing cyclophosphamide over ASCT, Dr Morris said. Nevertheless, he added, it is worthwhile to determine the genetic profile of patients with myeloma at relapse. “It helps you talking to the patient because you can give them a little bit of guidance of whether there’s a great chance of getting median survival of 5 to 7 years, which is what we expect now, or whether they should be a little more prepared that things might not go that well.”
“The study does support genomic profiling at time of diagnosis and relapse,” said Kenneth Anderson, MD, Kraft Family Professor of Medicine at Harvard Medical School, who was not involved in the Myeloma X trial. This is typically done in the United States, he added, either by FISH or increasingly by sequencing a panel of genes, which gives more cytogenetic information than in the British study.
It was not surprising, Dr Anderson said, that patients in this study with chromosomal abnormalities at time of relapse fared more poorly. “I think you can fairly say that, whatever the therapy is at the time of initial therapy or at the time of relapse, a high-risk lesion does portend a worse outcome than standard-risk myeloma,” Dr Anderson said.
Notably, for a subset of patients, high-risk lesions were detected only at diagnosis or at relapse. Of the 41 individuals in the study who had cytogenetic data available from both time points, 2 (4.9%) appeared to lose lesions that had been detected at diagnosis at relapse and 5 (12.2%) had lesions at relapse that were not detected at diagnosis. Although it has been pretty well accepted that patients can switch cytogenetic risk groups, this trial helped confirm that possibility, Dr Anderson said.
Dr Morris calls the study a “game changer” because it demonstrates that ASCT improves clinical outcome at the time of first relapse — and even at second or third relapse — based on the individuals who switched from cyclophosphamide to ASCT.
However, Dr Anderson noted that the study compared ASCT to cyclophosphamide, which is an outdated therapy for relapsed MM. “We have these active agents now, second-generation proteasome inhibitors, second-generation immunomodulatory drugs, and monoclonal antibodies, and even in relapsed myeloma, they can give many years of progression-free and overall survival,” he said.
In the US, Dr Anderson said, the standard treatment at time of diagnosis is triplet therapy featuring immunomodulatory drugs along with a transplant, followed by maintenance therapy, and if the patient relapses, the receipt of a triplet of novel second-generation agents and possibly a second transplant (provided the individual saw a good benefit from the first transplant).
- Cook G, Royle KL, O’Connor S, et al. The impact of cytogenetics on duration of response and overall survival in patients with relapsed multiple myeloma (long-term follow-up results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial [published online February 6, 2019]. Br J Haematol. doi: 10.1111/bjh.15782
- Cook G, Williams C, Brown JM, et al. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(8):874-885.
- Cook G, Ashcroft AJ, Cairns DA, et al. The effect of salvage autologous stem-cell transplantation on overall survival in patients with relapsed multiple myeloma (final results from BSBMT/UKMF Myeloma X Relapse [Intensive]): a randomised, open-label, phase 3 trial. Lancet Haematol. 2016;3(7):e340-e351.