Multiomics Profiling of Measurable Residual Disease (MRD) for Understanding the Biology of Ultra-Drug Resistance in Multiple Myeloma (MM)
Achieving undetectable MRD has become an endpoint in MM. However, there is a considerable fraction of patients (pts) with positive MRD after initial therapy. Emerging data suggests that prolonged treatment using the same drugs does not abrogate the poor prognosis of persistent MRD. Because these cells embody the notion of ultra-drug resistance, it could be hypothesized that a better understanding of MRD biology is needed to eradicate it and improve outcomes in MM.
Transcriptional analysis of patient-paired tumor cells at diagnosis vs persistent MRD after Rd in elderly MM and KRD/VRD induction in transplant-eligible pts, revealed differential expression of only 11 and 15 genes, respectively. By contrast, there were 646 differentially expressed genes between diagnosis and persistent MRD after HDT/ASCT, and 252 after consolidation. Genes commonly deregulated in MRD post HDT/ASCT and consolidation vs tumor cells at diagnosis in pts who relapsed, were enriched in biological processes involving cell activation in immune response.
We present the largest dataset of longitudinal MRD profiling in MM. Our results reveal transcriptional stability during induction with relative divergence after HDT/ASCT, as well as progressive genomic evolution that peaked after HDT/ASCT. These findings could help explain the continued responses with longer induction regimens, and limited efficacy of consolidation after HDT/ASCT observed in recent studies. Furthermore, the transcriptional and genomic singularity of MRD cells when compared to diagnosis and relapse, suggests that using drugs with alternative modes of action are needed to overcome MRD resistance.
ASH 2022: Abstract #99
Camila Guerrero, MSc, Noemi Puig, MD, PhD, Maria Teresa Cedena Romero, MD, PhD, Ibai Goicoechea, PhD, Leire Burgos, Diego Alignani, PhD, Aitziber Lopez, Sarai Sarvide, María José Calasanz, PhD, Ramon Garcia-Sanz, MD, PhD, Joaquin Martinez-Lopez, MD PhD, Laura Rosiñol, MD, PhD, Esther González Garcia, MD, Albert Oriol, MD, Rafael Rios, MD, PhD, Estrella Carrillo-Cruz, MD, Marta Sonia Gonzalez Perez, MD, Carmen Montes Gaisan, MD, Felipe De Arriba, PhD, Jose Maria Arguiñano, MD, Josep M Marti, MD, Yolanda Gonzalez-Montes, MD, Antonio Garcia-Guiñon, MD, Juan-José Lahuerta, MD, PhD, Joan Bladé Creixenti, MD, PhD, Maria-Victoria Mateos, MD, Jesús San-Miguel, MD, PhD and Bruno Paiva
Doctor Bio:
Camila Guerrero is a PhD student at the Onco-hematology Department at CIMA (Clínica Universidad de Navarra). She is currently researching multiple myeloma in a bioinformatics context of big data, machine learning, next generation flow cytometry, and multi-omic techniques.
