ASH 2023 | OPTIMUM/MUKnine: the risk of early relapse in patients with ultra high-risk multiple myeloma
Martin Kaiser, MD, FRCP, FRCPath, The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust, London, UK, discusses the findings of the genetic and gene expression profiling analysis, which aimed to determine factors associated with early relapse in patients enrolled in the OPTIMUM/MUKnine (NCT03188172) trial. Patients in this trial had ultra-high risk newly diagnosed multiple myeloma (NDMM) or primary plasma cell leukemia (pPCL) and, at the 18-month follow-up, 20% had relapsed following a quintuplet induction with daratumumab, low-dose cyclophosphamide, lenalidomide, bortezomib, and dexamethasone (Dara-CVRd) and extended consolidation and maintenance therapy with Dara-VRd. The cytogenetic analysis revealed that early relapse was associated with the presence of 3 or more high-risk cytogenetic abnormalities or with a SKY92 high-risk signature with or without the presence of 17p deletion. This interview took place at the 65th ASH Annual Meeting and Exposition, held in San Diego, CA.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript (edited for clarity)
We’re showing data this year from the OPTIMUM/MUKnine trial. We presented last year primary endpoint outcomes for this trial, where we treated patients with ultra high-risk myeloma, or plasma cell leukemia, with a quintuplet induction with Dara-CVRd and then an extended consolidation and maintenance therapy with Dara-VRd. We noticed very good outcomes and I think the follow-on is ongoing. We will present more data on the long-term outcome next year...
We’re showing data this year from the OPTIMUM/MUKnine trial. We presented last year primary endpoint outcomes for this trial, where we treated patients with ultra high-risk myeloma, or plasma cell leukemia, with a quintuplet induction with Dara-CVRd and then an extended consolidation and maintenance therapy with Dara-VRd. We noticed very good outcomes and I think the follow-on is ongoing. We will present more data on the long-term outcome next year. But we noticed that within the first 18 months, unfortunately, about 20% of patients do relapse.
We had very comprehensive genetic and gene expression profiling in this trial, so we have leveraged this advantage that we have in OPTIMUM/MUKnine to now look for factors that are associated with an early relapse, despite this very intensive and innovative treatment approach. We identified factors that are associated with an early relapse. We particularly found the co-occurance of three or more high-risk markers, so three genetic markers and/or gene expression profiling, to really have an additive effect on the risk of relapse. So these patients that have a combination of these markers are definitely enriched in the group that has an early relapse. So that’s quite an interesting finding. We also found a link with deletion 17p to be particularly enriched in all of these features that I’ve just mentioned. And it’s actually striking that other markers that we probably traditionally associate with adverse outcomes, such as ISS3, was not really associated with this group of relapse at 18 months and early relapse group. So we think the the significance of these findings is of course important in terms of treatments, paradigms are changing.
We’re seeing at this conference as well that overall for all comers, even we are thinking about potentially regimens such as PERSEUS, which is a late breaking abstract here. But there is still going to be a group of patients with unmet need and we need to address that and particularly identify new strategies moving forward. We think that our work is really playing a role there, particularly because the diagnostics that we’re using are applicable in diagnostic laboratories, in theory, worldwide.
Read more...
Disclosures
Karyopharm: Consultancy; Celgene/BMS: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; Seagen: Consultancy; Pfizer: Consultancy; Regeneron: Consultancy; Janssen: Consultancy, Honoraria; GSK: Consultancy.
