In a report published in the British Journal of Haematology, researchers found that following first relapse after a prior autologous stem cell transplantation (ASCT), most patients with multiple myeloma (MM) retain the cytogenetic profile they had at diagnosis. However, some patients appeared to develop adverse cytogenetic characteristics, and others lost theirs, features that have not previously been reported in cases of MM.

The researchers disclosed the most recent findings from the BSBMT/UKMF Myeloma X Relapse (Intensive) trial (ClinicalTrials.gov Identifier: NCT00747877) in which 174 patients with MM were randomly assigned to receive either salvage ASCT (89 patients) or weekly cyclophosphamide following reinduction therapy (85 patients). In this report, the researchers used interphase fluorescence in situ hybridization (iFISH) to investigate the influence of cytogenetics on time to progression (TTP), overall survival (OS), and progression-free survival (PFS). Researchers also assessed the outcomes for patients who received a post-trial ASCT after receiving weekly cyclophosphamide.

Cytogenetic data were available for 41 patients. ASCT was found to be associated with improved TTP (19 months vs 11 months) and reduced hazard of disease progression (hazard ratio, 0.40; P <.001) compared with cyclophosphamide at a median follow‐up of 76 months.

ASCT was also associated with improved OS (67 months vs 55 months) and PFS (19 months vs 11 months), with evidence of a detrimental influence on outcomes due to MYC rearrangement. Patients who received ASCT after weekly cyclophosphamide exhibited increased median OS as well (not reached vs 31 months).

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Analysis confirmed that the gains in TTP, PFS, and OS attributable to ASCT that were observed in prior reports on the Myeloma X trial are robust even at a longer follow‐up. Additionally, the analysis further supported the benefit of salvage ASCT after second relapse.

The researchers found that some adverse prognostic factors were both improved in some patients and worsened in others. “The genomic landscape with relapsing disease can vary from that seen at diagnosis with both loss and gain of adverse iFISH prognostic factors and confirm that the gain of such factors does affect prognosis in patients at first relapse,” concluded the researchers. They noted that their findings may inform a better understanding of the clonal genetic landscape in the setting of ASCT and salvage ASCT in relapsed MM.

Reference

1. 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]. doi: 10.1111/bjh.15782